The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≥ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

With the advent of big data era, our thinking, technology and methodology are being transformed. Data-intensive scientific discovery based on big data, named “The Fourth Paradigm,” has become a new paradigm of scientific research. Along with the development and application of the Internet information technology in the field of healthcare, individual health records, clinical data of diagnosis and treatment, and genomic data have been accumulated dramatically, which generates big data in medical field for clinical research and assessment. With the support of big data, the defects and weakness may be overcome in the methodology of the conventional clinical evaluation based on sampling. Our research target shifts from the “causality inference” to “correlativity analysis.” This not only facilitates the evaluation of individualized treatment, disease prediction, prevention and prognosis, but also is suitable for the practice of preventive healthcare and symptom pattern differentiation for treatment in terms of traditional Chinese medicine (TCM), and for the post-marketing evaluation of Chinese patent medicines. To conduct clinical studies involved in big data in TCM domain, top level design is needed and should be performed orderly. The fundamental construction and innovation studies should be strengthened in the sections of data platform creation, data analysis technology and big-data professionals fostering and training.

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

Among various genera of free-living amoebae prevalent in nature, some members are identified as causative agents of human encephalitis, in which Naegleria fowleri followed by Acanthamoeba spp. and Balamuthia mandrillaris have been successively discovered. As the three dominant genera responsible for infections, Acanthamoeba and Balamuthia work as opportunistic pathogens of granulomatous amoebic encephalitis in immunocompetent and immunocompromised individuals, whereas Naegleria induces primary amoebic meningoencephalitis mostly in healthy children and young adults as a more violent and deadly disease. Due to the lack of typical symptoms and laboratory findings, all these amoebic encephalitic diseases are difficult to diagnose. Considering that subsequent therapies are also affected, all these brain infections cause significant mortality worldwide, with more than 90% of the cases being fatal. Along with global warming and population explosion, expanding areas of human and amoebae activity in some regions lead to increased contact, resulting in more serious infections and drawing increased public attention. In this review, we summarize the present information of these pathogenic free-living amoebae, including their phylogeny, classification, biology, and ecology. The mechanisms of pathogenesis, immunology, pathophysiology, clinical manifestations, epidemiology, diagnosis, and therapies are also discussed.

The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER=1.95, P=0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.

In December 2019, an outbreak of novel coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ~2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

Spinal disease is an important cause of cervical discomfort, low back pain, radiating pain in the limbs, and neurogenic intermittent claudication, and its incidence is increasing annually. From the etiological viewpoint, these symptoms are directly caused by the compression of the spinal cord, nerve roots, and blood vessels and are most effectively treated with surgery. Spinal surgeries are primarily performed using two different techniques: spinal canal decompression and internal fixation. In the past, tactile sensation was the primary method used by surgeons to understand the state of the tissue within the operating area. However, this method has several disadvantages because of its subjectivity. Therefore, it has become the focus of spinal surgery research so as to strengthen the objectivity of tissue state recognition, improve the accuracy of safe area location, and avoid surgical injury to tissues. Aside from traditional imaging methods, surgical sensing techniques based on force, bioelectrical impedance, and other methods have been gradually developed and tested in the clinical setting. This article reviews the progress of different tissue state recognition methods in spinal surgery and summarizes their advantages and disadvantages.

Anti-β₂ glycoprotein I (anti-β₂GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β₂GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β₂GP I antibodies in complexes with β₂GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β₂GP I /β₂GP I complex. The interaction between the anti-β₂GP I /β₂GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B₂ production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β₂GP I /β₂GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β₂GP I /β₂GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

The aim of this paper was to investigate the effects of resistin on human umbilical vein endothelial cells (HUVECs), and to explore its role and mechanism of action in atherosclerosis. HUVECs were incubated with recombinant human resistin (0, 50, 100 ng/mL) for 24 h. ICAM-1, VCAM-1 and reactive oxygen species (ROS) were assayed by flow cytometer. ET-1, eNOS and iNOS mRNA expression were measured by semi-quantitative RT-PCR. Incubation of HUVECs with resistin resulted in an increase in ICAM-1 expression and ET-1 mRNA expression. However, resistin had no effect on VCAM-1 expression and ROS release. eNOS and iNOS mRNA expression were not altered by resistin stimulation. Adipokine resistin exerted a direct effect in promoting HUVEC dysfunction by promoting ICAM-1 and ET-1 expression. These data suggest that adipocyteendothelium cross-talk might play an important role in the pathogenesis of cardiovascular disease in diabetes mellitus.

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

Coronavirus disease 2019 (COVID-19) is currently under a global pandemic trend. The efficiency of containment measures and epidemic tendency of typical countries should be assessed. In this study, the efficiency of prevention and control measures in China, Italy, Iran, South Korea, and Japan was assessed, and the COVID-19 epidemic tendency among these countries was compared. Results showed that the effective reproduction number(Re) in Wuhan, China increased almost exponentially, reaching a maximum of 3.98 before a lockdown and rapidly decreased to below 1 due to containment and mitigation strategies of the Chinese government. The Re in Italy declined at a slower pace than that in China after the implementation of prevention and control measures. The Re in Iran showed a certain decline after the establishment of a national epidemic control command, and an evident stationary phase occurred because the best window period for the prevention and control of the epidemic was missed. The epidemic in Japan and South Korea reoccurred several times with the Re fluctuating greatly. The epidemic has hardly rebounded in China due to the implementation of prevention and control strategies and the effective enforcement of policies. Other countries suffering from the epidemic could learn from the Chinese experience in containing COVID-19.

New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR⁺/HER2^-- advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR⁺/HER2^-- ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, P<0.001), overall survival (pooled HR= 0.755, P<0.001), and tumor response rates (ORR, pooled OR= 1.478, P<0.001; CBR, pooled OR= 1.201, P<0.001) with manageable toxicities (pooled OR= 3.280, P<0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, P<0.001) yet pronounced toxicities (pooled OR=2.154, P<0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.

Dyspnea is one of the most common manifestations of patients with pulmonary disease, myocardial dysfunction, and neuromuscular disorder, among other conditions. Identifying the causes of dyspnea in clinical practice, especially for the general practitioner, remains a challenge. This pilot study aimed to develop a computer-aided tool for improving the efficiency of differential diagnosis. The disease set with dyspnea as the chief complaint was established on the basis of clinical experience and epidemiological data. Differential diagnosis approaches were established and optimized by clinical experts. The artificial intelligence (AI) diagnosis model was constructed according to the dynamic uncertain causality graph knowledge-based editor. Twenty-eight diseases and syndromes were included in the disease set. The model contained 132 variables of symptoms, signs, and serological and imaging parameters. Medical records from the electronic hospital records of Suining Central Hospital were randomly selected. A total of 202 discharged patients with dyspnea as the chief complaint were included for verification, in which the diagnoses of 195 cases were coincident with the record certified as correct. The overall diagnostic accuracy rate of the model was 96.5%. In conclusion, the diagnostic accuracy of the AI model is promising and may compensate for the limitation of medical experience.

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.

p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type p53 or the functional activation of mutant-type p53 might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150 with wild-type p53, p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the p53 genotype.

The effect of peripherally administered oxytocin (OT) on gastric ischemia-reperfusion injury (GI-RI) and its possible mechanism were investigated. The Sprague-Dawley (SD) rats were randomly divided into different treatment groups (n = 6). The animal GI-RI model was established by clamping the celiac artery for 30 min to induce ischemia and then released to allow reperfusion for 1 h, and the degree of GI-RI was assessed by scoring the gastric mucosal damage index (GMDI), the gastric fluid output, gastric fluid output, gastric acidity were measured and the surgical preparations of vagotomy and sympathectomy were used to investigate the possible mechanism of OT on GI-RI. The results were as follows. Compared with the control group (NS plus GI-R only, GMDI 121.33±10.40, n = 6), the intra peritoneal (ip) administration of oxytocin (20, 100 μg/0.5 mL) obviously attenuated GI-RI (P<0.05), GMDI were 82.33±14.26, 53.5±5.58 respectively (n = 6); the gastric fluid output and the gastric acidity (evaluated by pH) of the control group were (430.17±87.36) μL, 1.55±0.25 (n = 6), and those of the OT group were (102.45±48.00) μL, 2.65±0.40 (n = 6) res pectively; differences had statistical significance (P<0.01). The effect of oxytocin was reversed by atosiban, a selective oxytocin receptor antagonist. The GMDI of the group given atosiban 10 min before OT was 138.17±24.06 (n = 6), which had no significant difference with the control group. Oxytocin further attenuated GI-RI after vagotomy and sympathectomy (GMDI 6.83±8.89, 29.67±5.54, n = 6), compared with the GI-R group and the oxytocin group (P<0.01). These results indicated that the oxytocin could significantly protect gastric mucosal against injury induced by ischemia-reperfusion, and the oxytocin receptor was involved. This effect of oxytocin may be mediated through the vagus and sympathetic nerve, and then lead to the reduction of gastric juice output and the depression of gastric acidity.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

The effects of heat stress on the neurons in hippocampal CA1 region of brain ischemia/reperfusion were explored. The mice were pretreated with heat stress followed by ischemia/reperfusion by clipping bilateral cervical commo n arteries for 7 min. Mice were divided randomly into four groups as follows: (1) normal control group; (2) heat stress pretreated subsequent to ischemia/reperfusion group (HS/IR); (3) ischemia/reperfusion group (IR); and (4) heat stress group (HS). Animals in the last three groups were subdivided into three subgroups: 1 d, 4 d, 14 d respectively. The Morris water maze was used to test the ability of learning and memorizing, Nissl staining was used to count the average number of survived neurons in hippocampal CA1 region, and immunohistochemistry combined with image analysis system to detect the changes of Microtubule associated protein 2 (MAP-2) expression. The results showed that mice in IR group exhibited increased escape latency when compared with that of normal, HS and HS/IR groups (P<0.01), and the mice in IR group adopted an inefficient search strategy, major in circling and restricted searching manners. Nissl staining results showed a significant reduction in the number of pyramidal neurons in hippocampal CA1 regions in HS/IR and IR groups, with a decrease in IR group (P<0.01). Compared with normal group, the expression of MAP-2 in hippocampal CA1 region obviously decreased in IR group (P<0.05). The present results indicate that heat stress pretreatment can improve the spatial learning and memorizing function through protection to hippocampal neurons.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

Diabetes mellitus is one of the major public health problems worldwide. Considerable recent evidence suggests that the cellular reduction–oxidation (redox) imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in β-cell dysfunction and insulin resistance. Reactive oxide species (ROS) can also directly oxidize certain proteins (defined as redox modification) involved in the diabetes process. There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility, storage instability and non-selectivity of antioxidants. Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS. We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus. Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes.

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P<0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30–32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1, 2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.