ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis （RA） in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information， clinical data， laboratory test results， and traditional Chinese medicine （TCM） symptom information were collected for syndrome differentiation， on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study， including 88 （34.1%） patients with cold dampness obstruction syndrome， 53 （20.5%） patients with dampness and heat obstruction syndrome， 31 （12.0%） patients with wind dampness obstruction syndrome， 29 （11.2%） patients with liver-kidney deficiency syndrome， 19 （7.4%） patients with Qi-blood deficiency syndrome， 14 （5.4%） patients with phlegm-stasis obstruction syndrome， 15 （5.8%） patients with stasis obstructing collateral syndrome and 9 （3.5%） patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever， 28-tender joint count （TJC28）， and 28-joint disease activity score （DAS28）-C-reactive protein （CRP） and higher central sensitization， cold feeling of joints， fear of wind and cold， cold limbs， and abdominal distention than the group of other syndromes （P<0.05）. The binary logistic regression analysis showed that central sensitization （OR 5.749， 95%CI 2.116-15.616， P<0.001） and DAS28-CRP （OR 0.600， 95% CI 0.418-0.862， P=0.006） were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization， cold feeling of joints， abdominal distension and may be a clinical syndrome associated with central sensitization.

Previous studies have shown that the diversity and composition of intestinal microbiota are related to the effect of tumor immunotherapy,but the mechanism of intestinal microbiota affecting tumor immunotherapy resistance has rarely been sum-marized.This article not only expounds the current clinical sta-tus of tumor immunotherapy resistance,but also summarizes the correlation and regulatory mechanism between the composition and homeostasis of intestinal microbiota and drug resistance to different types of tumor immunotherapy,so as to provide a refer-ence for the study of potential targets for improving tumor immu-notherapy resistance based on intestinal microbiota.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20％.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective To investigate the effect of vitamin B12(VB12)on the expression of zonula occludens-1(ZO-1)in house dust mite(HDM)-treated human airway epithelial cell line(Beas-2b)and its underlying mechanism.Methods Beas-2b cells were cultured in DMEM high-glucose medium containing 10%fetal bovine serum.The cells were divided into four groups:control,VB12,HDM,and VB12+HDM.Beas-2b cells were trans-fected with lentiviruses carrying NC-siRNA,ATG5-siRNA,BECN1-siRNA,and mCherry-EGFP-LC3.After 12 hours of transfection(MOI=20),the medium was replaced with fresh medium,and stable transfected cell lines were selected using puromycin(1 μg/mL).Cells were stimulated with VB12(20 μg/mL)and HDM(50 μg/mL)for 24 hours.The protein levels of ZO-1,autophagy-related protein 5(ATG5),BECN1 and microtubule-associated protein light chain 3(LC3)were detected by immunofluorescence and Western blot.Autophagy in human airway epithelial cells was observed using confocal microscopy.Results Compared with the control group,the expression of ZO-1 in the HDM group was lower(P<0.05),while the expressions of ATG5,BECN1,and LC3 were higher(P<0.05).Compared with the HDM group,the VB12+HDM group showed increased ZO-1 expression(P<0.05),decreased expressions of ATG5,BECN1,and LC3(P<0.01),and reduced autophagosome formation(P<0.05).In ATG5-and BECN1-knockdown cell lines,ZO-1 expression increased after HDM treatment(P<0.05).Conclusion Vb12 can enhance ZO-1 expression in HDM-treated human airway epithelial cells by down-regulating autophagy,and its mechanism is associated with the ATG5 and BECN1 signaling pathways.

Peripheral artery disease(PAD),commonly encountered in vascular surgery,predominantly affects the lower limbs and presents with ischemic symptoms resulting from atherosclerosis.It carries risks of adverse limb events and cardiovascular events.Antithrombotic therapy remains a cornerstone in the management of PAD.This article reviews the evidence and research progress regarding dual-pathway antithrombotic therapy for PAD.Multiple clinical trials have demonstrated that,compared to single antiplatelet therapy,dual-pathway antithrombotic therapy significantly reduces the risks of major adverse limb events and major adverse cardiovascular events without a significant increase in bleeding risk.For high-risk patients,such as those with advanced age,multivessel disease,comorbid coronary artery disease,or those undergoing endovascular revascularization,the benefits of dual-pathway antithrombotic therapy are particularly pronounced.Current clinical guidelines have incorporated dual-pathway antithrombotic therapy into their recommendations,standardized criteria for identifying the most appropriate patient populations remain lacking.Despite its advantages in reducing adverse events,its long-term safety profile and optimal target populations warrant further investigation.

Objective To investigate the effect of vitamin B12(VB12)on the expression of zonula occludens-1(ZO-1)in house dust mite(HDM)-treated human airway epithelial cell line(Beas-2b)and its underlying mechanism.Methods Beas-2b cells were cultured in DMEM high-glucose medium containing 10%fetal bovine serum.The cells were divided into four groups:control,VB12,HDM,and VB12+HDM.Beas-2b cells were trans-fected with lentiviruses carrying NC-siRNA,ATG5-siRNA,BECN1-siRNA,and mCherry-EGFP-LC3.After 12 hours of transfection(MOI=20),the medium was replaced with fresh medium,and stable transfected cell lines were selected using puromycin(1 μg/mL).Cells were stimulated with VB12(20 μg/mL)and HDM(50 μg/mL)for 24 hours.The protein levels of ZO-1,autophagy-related protein 5(ATG5),BECN1 and microtubule-associated protein light chain 3(LC3)were detected by immunofluorescence and Western blot.Autophagy in human airway epithelial cells was observed using confocal microscopy.Results Compared with the control group,the expression of ZO-1 in the HDM group was lower(P<0.05),while the expressions of ATG5,BECN1,and LC3 were higher(P<0.05).Compared with the HDM group,the VB12+HDM group showed increased ZO-1 expression(P<0.05),decreased expressions of ATG5,BECN1,and LC3(P<0.01),and reduced autophagosome formation(P<0.05).In ATG5-and BECN1-knockdown cell lines,ZO-1 expression increased after HDM treatment(P<0.05).Conclusion Vb12 can enhance ZO-1 expression in HDM-treated human airway epithelial cells by down-regulating autophagy,and its mechanism is associated with the ATG5 and BECN1 signaling pathways.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.