Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Aim To investigate the regulatory and an-ti-tumour effects of baicalein on mouse hepatocellular carcinoma cells and mouse macrophage co-cultures.Methods In vitro experiments,mouse hepatocellular carcinoma cell H22 and mouse macrophage RAW264.7 were randomly divided into a blank group and different concentrations of gradient administration group(5,10,20,40,80 mg·L-1),and the cell activity was detec-ted by CCK-8 assay;the two kinds of cells were co-cultured in Transwell chambers of 6-well plates for 48 h,and were randomly divided into the blank,model,and low,medium,and high baicalin groups(10,20,40 mg·L-1).Cell scratch and invasion assays,ELISA kits were used to detect TNF-α and IL-10 factor levels,and Western blot was used to determine the lev-els of CCNA2 and related proteins.The levels of TNF-α and IL-10 were detected by ELISA kits,and the ex-pression levels of CCNA2 and related proteins were de-tected by Western blot.In vivo experiments,H22 sub-cutaneous tumour model was established and randomly divided into the blank,positive,model and drug-ad-ministered groups.Mouse spleen,thymus and tumour indices were counted,and immunohistochemistry and Western blot were employed to detect the expression levels of CCNA2 and macrophage-related indexes in tumour tissues.Results Different doses of baicalein had a significant inhibitory effect on H22 and no signif-icant cytotoxicity on M0-type RAW264.7;the mor-phology of M0-type RAW264.7 cells was changed after co-culture,TNF-α was elevated and IL-10 was re-duced in the baicalein group;the results of the cell scratch assay and invasion assay found that baicalein inhibited M2-type macrophage invasion and metastasis;Arg1,p-p38/p38,p-stat3/stat3,N-cadherin,CCNA2 decreased significantly and Inos and E-cadherin in-creased significantly in the baicalein group;CCNA2,CD206 expression decreased significantly and CD86 expression increased significantly in the administered group.Conclusions Baicalein reverses M2-type mac-rophage polarisation and pro-carcinogenic functions and inhibits M2-type macrophage migration and invasion by modulating M2-type macrophage-related signalling pathways.

Glutamate,norepinephrine,and their receptors com-prise the glutamatergic and norepinephrine systems,which mu-tually affect each other and play essential roles in mediating vari-ous neuropsychiatric diseases.This paper reviews the functions of N-methyl-D-aspartate receptor(NMDA-R)and α2-adrenergic receptor(α2-AR)and their functional crosstalk at the molecular level in brain in common neuropsychiatric diseases,which would benefit our understanding of neuropathophysiology of psychiatric diseases,drug development and optimization of clinical neuro-psychopharmacology.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

Objective To evaluate the clinical effect of a new three-phase Chinese medicine(CM)external treatment for acute lateral ankle ligament injuries.Methods From July to December 2023,64 patients with acute lateral ankle ligament in-juries were randomly assigned to receive either the new three-phase CM external treatment combined with the POLICE(pro-tect,optimal loading,ice,compression,elevation)treatment(observation group)or the POLICE treatment(control group),with 32 cases in each group.The observation group consisted of 17 males and 15 females,with an average age of(30.59±3.10)years old ranging from 25 to 36 years old,while the control group included 14 males and 18 females,with an average age of(30.03±3.19)years old ranging from 24 to 37 years old.Visual analogue scale(VAS)evaluation and Figure of 8 measurement were used to evaluate the degree of ankle joint pain and swelling of the subjects at the initial enrollment and after 1 week and sixth weeks of treatment.At the same time,the American Orthopaedic Foot and Ankle Society(AOFAS)and Karlsson Ankle Function Score System were used to evaluate the improvement of ankle joint function in patients at all stages.MRI imaging was employed to observe the degree of biological healing of the anterior talofibular ligament,with the signal to noise ratio(SNR)in-dicating the level of healing.A lower SNR suggests better ligament healing,as it represents lower water content in the ligament.Results All patients completed a 6-week follow-up.There was no significant difference in VAS,AOFAS score and Karlsson score between the two groups before treatment(P＞0.05).After 1 week and 6 weeks of treatment,the VAS,AOFAS score and Karlsson score of the two groups were significantly improved(P＜0.05).After 1 week of treatment,the VAS score of the obser-vation group(3.21±0.87)was lower than that of the control group(4.21±1.50),and the difference was statistically significant(P＜0.05).After 1 weeks of treatment,the AOFAS and Karlsson scores[(50.84±4.70)points,(49.97±4.00)points]of the ob-servation group were higher than those[(46.91±5.56)points,(46.66±5.36)points]of the control group(P＜0.05).MRI images showed that after 6 weeks of treatment,the SNR value of the observation group was significantly lower than that of the control group,and the difference was statistically significant(SNR of the observation group was 75.25±16.59,the contral gruop was 85.81±15.55),(P＜0.05).Conclusion Compared with the control group,the new three-phase CM external treatment is signifi-cantly effective in reducing pain and swelling,enhancing ligament repair quality,and promoting functional recovery of the an-kle joint in patients with acute lateral malleolar ligament injuries.

H9N2 is a low-pathogenic avian influenza subtype that has a significant impact on the global poultry industry.Since 1994,H9N2 has continuously mutated as a zoonotic pathogen in China,thus posing a severe threat to the poultry indus-try as well as human life and health.In particular,gene rearrangements and recombinations between H9N2 and other influenza viruses have increased the likelihood of avian influenza viruses crossing species barriers and infecting humans and other mam-mals,thereby posing new threats to global public health.Therefore,this article aims to provide a brief discussion of the epide-miology and vaccine research progress related to the H9N2 virus,serving as a valuable resource for safeguarding the economy of the poultry industry and global public health security.

Enteropathogenic Escherichia coli(EPEC),a zoonotic foodborne pathogen,can induce severe and prolonged di-arrhea,thus substantially affecting global public health safety.To understand the pathogenicity of EPEC and its potential risk to human health,this study investigated the antimicrobial resistance and genome-wide characteristics of EPEC originating from ducks.After identification of EPEC with the plate method and PCR,antimicrobial susceptibility of the isolates was examined with the microbroth dilution method.In addition,analyses of serotype,sequence type(ST),and plasmid incompatibility groups were conducted with whole-genome sequencing(WGS)and bioinformatic methods.Ten EPEC isolates were identified,including serotypes O71∶H40 and O3∶H21.All EPEC strains exhibited multiple drug resistance.The highest proportion of resistance(100％)was observed to ciprofloxacin,streptomycin,tetracycline,and polymyxin B.In contrast,the isolates showed susceptibility to cefoxitin,amikacin,and imipenem.Furthermore,all strains carried the tetracycline resistance gene tet(A)and extended-spectrum β-lactamase(ESBL)resistance genes,including blaOXA-10,blaTEM-1A,and blaTEM-1B.Various virulence genes,associated primarily with the secretory system,were de-tected in the isolates.However,no bf p genes or per ARC genes were identified,thus indicating that the EPEC isolates were atypical EPEC(aEPEC).The results demonstrated the presence of multiple antimicrobial resistance,multiple resistance and viru-lence genes,and various plasmid incompatibility groups,thus in-dicating potential pathogenicity to humans.Strengthened monitoring of duck-derived EPEC is crucial to effectively control the spread of the pathogen and safeguard public health.

Objective:To evaluate the clinical and prognostic value of prothrombin time(PT)and activated partial thromboplastin time(APTT)in newly diagnosed patients with multiple myeloma(MM).Methods:The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively,and the patients were divided into two groups:normal PT and APTT group and prolonged PT or APTT group.The differences in sex,age,classification,staging,bleeding events,laboratory indicators[including hemoglobin(Hb),platelet count(PLT),serum calcium,serum albumin(ALB),lactate dehydrogenase(LDH),serum creatinine and β 2-microglobulin],and cytogenetic characteristics between the two groups of patients were compared.The effect of prolonged PT or APTT on survival of patients with MM was analyzed.Results:Compared with patients in normal PT and APTT group,patients in prolonged PT or APTT group were more likely to experience bleeding events(x2=5.087,P=0.024),with lower ALB levels(x2=4.962,P=0.026)and PLT levels(x2=4.309,P=0.038),and higher serum calcium levels(x2=5.056,P=0.025).The positive rates of del17p,del13q and 1q21+in prolonged PT or APTT group were higher than those in normal PT and APTT group,but the difference was not statistically significant(P＞0.05).K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival(PFS)(P=0.032)and overall survival(OS)(P=0.032).Multivariate Cox analysis showed that prolonged PT or APTT(HR=2.1 16,95％CI:1.025-4.372,P=0.043)and age ≥65 years(HR=2.403,95％CI:1.195-4.836,P=0.014)were independent risk factor for OS in newly diagnosed MM patients.However,prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients(HR=1.162,95％CI:0.666-2.026,P=0.597).Conclusion:Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators,shorter PFS and OS.Prolonged PT or APTT is an independent risk factor for OS in MM patients.

Objective:To systematically evaluate the methodological quality and reporting quality of randomized controlled tri-als(RCT)on the treatment of BPH with traditional Chinese medicine(TCM),in order to provide some methodological reference for clinical practice and research.Methods:We searched CNKI,VIP,Wanfang Data and PubMed for RCTs on the treatment of BPH with TCM published in China from January 2013 to November 2023.Two researchers screened the literature separately,and evaluated the methodological and reporting quality of the RCTs based on the Cochrane bias risk assessment tool and CONSORT TCM compound.Results:Totally,88 RCTs were included in this study.In terms of methodological quality,according to the Cochrane bias risk assess-ment tool,27 biases in the process of randomization were identified as of low-risk and the other 61 of a certain risk.Among the alloca-tion-related biases deviating from the established interventions,76 were of low risk,10 of a certain risk and 2 of high risk;among the compliance-related biases deviating from the established interventions,76 were of low risk and 12 of a certain risk;among the biases due to missing outcome data,86 were of low risk and 2 of a certain risk,while all the biases due to outcome measurement were of low risk;and among the biases from selective reporting,65 were of low-risk,2 of a certain risk and 21 of high-risk.In terms of reporting quality,according to the evaluation criteria of consort TCM compound,appropriate key words were used in 1 RCT(0.01％),the ran-dom assignment sequence method described in 27(30.68％),the details of assignment limitation given in 5(5.68％),assignment concealment mentioned in 3(3.41％),the blind method and assignment concealment employed in 3(3.41％),fall-offs recorded in 10(11.36％),adverse events reported in 38(43.18％),and limitations of the trials analyzed in 18(20.45％).All the RCTs lacked complete intervention measures,subject flow chart,clinical trial registration and research schemes.Conclusion:At present,the methodological quality and reporting quality of RCTs on the treatment of BPH with TCM are generally low,with the main problems of incomplete experimental designs,lack of detailed description of randomized and blind methods,and insufficient TCM symptom eval-uation of outcome indicators.Researchers should be cautious in adopting and applying the results reported,follow the CONSORT state-ment in design,registration,implement and reporting of the scheme,fully consider the clinical characteristics of TCM in the treatment of BPH,and reasonably design and report the evaluation indicators.