Objective: To investigate the epidemiological characteristics of pulmonary tuberculosis (PTB) among residents aged 60 years and older in Yangzhou City, Jiangsu Province from 2013 to 2022, so as to provide the evidence for the improvement of PTB prevention and control measures in this population. Methods: Data of PTB cases aged 60 years and older in Yangzhou City from 2013 to 2022 were collected from the Chinese Disease Prevention and Control Information System. The temporal, population, and regional distribution characteristics of PTB cases were analyzed using the descriptive epidemiological method. Results: A total of 8 726 PTB cases aged 60 years and older were registered in Yangzhou City from 2013 to 2022, including 4 167 cases positive for pathogenic tests, with a positive rate of 47.75%. The registered incidence rates and the positive rates of pathogenic tests of PTB among residents aged 60 years and older in Yangzhou City showed downward trends from 2013 to 2022 (both P<0.05). The average annual registered incidence rate of PTB was 83.95/105, and the average annual registered incidence rate of PTB positive for pathogenic tests was 40.09/105. The average annual registered incidence rate of PTB in males was higher than that in females (138.57/105 vs. 31.76/105, P<0.05). The registered incidence rate of PTB showed an increasing trend with age (P<0.05), with the highest rate observed in the age group of 75-<80 years (110.37/105). The top three regions with the highest average annual registered incidence rates of PTB were Jiangdu District (94.34/105), Baoying County (91.61/105) and Hanjiang District (84.93/105). Conclusions The registered incidence of PTB among residents aged 60 years and older in Yangzhou City showed a downward trend from 2013 to 2022. Particular attention should be payed to males, residents aged 75- <80 years, and the elderly in Jiangdu District and Baoying County.

OBJECTIVE To determine the contents of 15 components in Aurantii Fructus Immaturus from different origins （Citrus aurantium， C. junos， C. aurantium Linn.， C. sinensis Osb.， C. sinensis）， screen differential components， and provide references for the quality evaluation of Aurantii Fructus Immaturus. METHODS HPLC method was adopted to determine the contents of synephrine， N-methyltyramine， 5，7-dihydroxychromone-7-neohesperidoside， neoponcirin， narirutin， naringin， hesperidin， neohesperidin， naringenin， hesperetin， sinensetin， nobiletin， tangeretin， 5-demethylnobiletin， and auraptene in 46 batches of Aurantii Fructus Immaturus from different origins. The determination was performed on Waters Symmetry C18 column with mobile phase consisted of acetonitrile-0.1% formic acid （gradient elution） at the flow rate of 1.0 mL/min； column temperature was set at 40 ℃ ， detection wavelength was 284 nm， and sample injection volume was 5 μL. The differences between different origins of Aurantii Fructus Immaturus were analyzed by cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and differential components were screened. RESULTS The linear relationships of the aforementioned 15 components were all good within the tested mass concentration ranges （all r＞0.999 0）. The RSDs for precision， stability （24 h）， and repeatability tests were all less than 2.00%. The average recovery rate ranged from 91.1% to 103.9% （all RSDs＜3.10%）. Cluster analysis， PCA， and OPLS-DA revealed that C. sinensis Osb. and C. sinensis were clustered into one category， while C. aurantium，C. junos and C. aurantium Linn. were clustered into another category. The variable importance projection values for neohesperidin， auraptene， naringin， neoponcirin， tangeretin， hesperidin， sinensetin， and 5，7-dihydroxychromone-7-neohesperidoside were all greater than 1. CONCLUSIONS In this study， the contents of 15 components in Aurantii Fructus Immaturus from different origins are determined， and 8 differential components， including neohesperidin， auraptene， naringin， and neoponcirin， are screened out.

Helicobacter pylori(H.pylori)infection triggers gastric mucosal inflammatory responses and spasmolytic polypeptide-expressing metaplasia(SPEM).These pathological conditions can escalate the severity of chronic gas-tritis,gastric ulcers and even cause gastric cancer.SPEM is frequently viewed as an early sign of gastric mucosal injury and the onset of carcinogenesis.A comprehensive analysis of the genesis and molecular regulation of SPEM cells in the context of H.pylori infection further has enlightened the pathogenesis of gastric mucosal diseases and provide new ideas and targets for diagnosing and treatment of H.pylori-related gastric mucosal diseases.This paper reviews a variety of molecular biomarkers associated with SPEM,encompassing TFF2,CD44v9,and AQP5,and delineates their pivotal regulatory functions in H.pylori infection and SPEM.This paper also reviews the origination of SPEM cells and pertinent molecular regulatory mechanisms.

Objective To investigate the detection rate of Klebsiella pneumoniae(KP)in the intestinal tract of intensive care unit(ICU)patients and community healthy adults,and analyze its virulence genes and drug resistance.Methods Fecal swabs or fecal specimens from ICU patients admitted to the Third Affiliated Hospital of Wenzhou Medical University and community healthy adults from December 2020 to December 2021 were collected for screening KP.The hypermucoviscosity(HM)phenotype was identified by the wire drawing test.The Vitek 2 automatic microbial analysis system and K-B disk diffusion method were used for detecting drug sus-ceptibility.PCR was used to screen extended spectrum β-lactamases(ESBLs),carbapenem resistance genes,9 virulence related genes,including allS,entB,fimH,iutA,kfu,magA,mrkD,rmpA,and ybtS,and 6 highly virulent capsule serotypes such as K1,K2,K5,K20,K54,and K57.Meanwhile,their multilocus sequence typing(MLST)was analyzed.Statistical analysis was conducted using SPSS 23.0 software.Results A total of 448 fecal samples were collected,including 140 from ICU patients and 308 from commu-nity healthy adults.A total of 89 strains of KP were isolated,including 36(25.7%)from ICU patients and 53(17.2%)from commu-nity healthy adults.The detection rate of KP in ICU patients was significantly higher than that in community healthy adults(χ2=4.375,P＜0.05).There were 9 strains(25%)of HMKP in ICU patients and 19 strains(35.8%)in community healthy adults,and there was no significant difference in the detection rate between them(χ2=1.170,P＞0.05).HMKP and KP detected in healthy adults were natu-rally resistant to ampicillin and still highly sensitive to commonly used antibiotics.The KP from ICU patients showed varying degrees of resistance to commonly used drugs.The resistance of the KP from ICU patients to cephalosporins,penicillinase inhibitors,carbapenem,quinolones,amtronam,gentamicin,amicacin and cotrimoxazole except for tobramycin was significantly higher than that from healthy a-dults(all P＜0.05).In addition,18 strains(50%)of KP producing ESBLs were detected,all of which were non-HM phenotypes.A-mong them,6 strains were carbapenem resistant KP(CRKP).Five strains of CRKP carrying KPC enzyme all belonged to ST11 type and 1 carrying NDM enzyme to ST1855 type.A total of 27(30.3%)strains of KP with highly virulent capsule serotypes were detected,mainly K1,K2,and K57,but no K5.There were no significant differences in the detection rates of 9 virulence genes and 5 highly vir-ulent capsule serotypes between ICU patients and healthy adults(all P＞0.05).High-risk ST types were detected in both ICU patients and healthy adults.Conclusion High virulence and high-risk KP strains are detected from the intestinal tract of healthy adults in this area,which increases the risk of infection transferring from community to hospital.In addition,carbapenemase-resistant ST11 is detec-ted from the intestinal tract of ICU patients,so the spread of drug-resistant plasmids should be highly vigilant.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Objective To investigate the detection rate of Klebsiella pneumoniae(KP)in the intestinal tract of intensive care unit(ICU)patients and community healthy adults,and analyze its virulence genes and drug resistance.Methods Fecal swabs or fecal specimens from ICU patients admitted to the Third Affiliated Hospital of Wenzhou Medical University and community healthy adults from December 2020 to December 2021 were collected for screening KP.The hypermucoviscosity(HM)phenotype was identified by the wire drawing test.The Vitek 2 automatic microbial analysis system and K-B disk diffusion method were used for detecting drug sus-ceptibility.PCR was used to screen extended spectrum β-lactamases(ESBLs),carbapenem resistance genes,9 virulence related genes,including allS,entB,fimH,iutA,kfu,magA,mrkD,rmpA,and ybtS,and 6 highly virulent capsule serotypes such as K1,K2,K5,K20,K54,and K57.Meanwhile,their multilocus sequence typing(MLST)was analyzed.Statistical analysis was conducted using SPSS 23.0 software.Results A total of 448 fecal samples were collected,including 140 from ICU patients and 308 from commu-nity healthy adults.A total of 89 strains of KP were isolated,including 36(25.7%)from ICU patients and 53(17.2%)from commu-nity healthy adults.The detection rate of KP in ICU patients was significantly higher than that in community healthy adults(χ2=4.375,P＜0.05).There were 9 strains(25%)of HMKP in ICU patients and 19 strains(35.8%)in community healthy adults,and there was no significant difference in the detection rate between them(χ2=1.170,P＞0.05).HMKP and KP detected in healthy adults were natu-rally resistant to ampicillin and still highly sensitive to commonly used antibiotics.The KP from ICU patients showed varying degrees of resistance to commonly used drugs.The resistance of the KP from ICU patients to cephalosporins,penicillinase inhibitors,carbapenem,quinolones,amtronam,gentamicin,amicacin and cotrimoxazole except for tobramycin was significantly higher than that from healthy a-dults(all P＜0.05).In addition,18 strains(50%)of KP producing ESBLs were detected,all of which were non-HM phenotypes.A-mong them,6 strains were carbapenem resistant KP(CRKP).Five strains of CRKP carrying KPC enzyme all belonged to ST11 type and 1 carrying NDM enzyme to ST1855 type.A total of 27(30.3%)strains of KP with highly virulent capsule serotypes were detected,mainly K1,K2,and K57,but no K5.There were no significant differences in the detection rates of 9 virulence genes and 5 highly vir-ulent capsule serotypes between ICU patients and healthy adults(all P＞0.05).High-risk ST types were detected in both ICU patients and healthy adults.Conclusion High virulence and high-risk KP strains are detected from the intestinal tract of healthy adults in this area,which increases the risk of infection transferring from community to hospital.In addition,carbapenemase-resistant ST11 is detec-ted from the intestinal tract of ICU patients,so the spread of drug-resistant plasmids should be highly vigilant.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Information on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Yangzhou City from 2012 to 2020 was obtained from the Information System of the Chinese Center for Disease Control and Prevention. The epidemic characteristics of RR-PTB patients were analyzed by using χ2 test. The average annual registered incidence rate of RR-PTB patients in Yangzhou City from 2012 to 2020 was 0.57/100 000, and the difference between the registered incidence rates in each year was statistically significant ( χ2=29.326, P<0.001). The proportion of re-treated patients (64.8%) was higher than that of newly treated patients (35.2%, χ2=50.593, P<0.001). The registered incidence rate in males (0.91/100 000) was higher than that in females (0.24/100 000, χ2=80.566, P<0.001). The age distribution showed that the highest incidence rate was in the age group≥60 years (0.96/100 000) and the lowest was in the age group 0-<45 years (0.31/100 000, χ2=55.853, P<0.001). From 2012 to 2020, Baoying County had the largest number of registered RR-PTB patients (44 cases), and its registered incidence rate (0.64/100 000) was only lower than that of Guangling District (0.98/100 000). The registered incidence rate of RR-PTB patients in Baoying County during 2016—2020 also increased significantly compared to 2012—2015 ( P=0.001). Logistic regression was used to analyze the factors related to the treatment outcome of RR-PTB patients. The results showed that patients aged≥60 years and those classified as the re-treatment were risk factors for successful treatment of RR-PTB patients ( P<0.05). In summary, males, people aged≥60 years, patients classified as the re-treatment, and residents of Baoying County should be the key populations for RR-PTB epidemic prevention and control in Yangzhou City.

Information on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Yangzhou City from 2012 to 2020 was obtained from the Information System of the Chinese Center for Disease Control and Prevention. The epidemic characteristics of RR-PTB patients were analyzed by using χ2 test. The average annual registered incidence rate of RR-PTB patients in Yangzhou City from 2012 to 2020 was 0.57/100 000, and the difference between the registered incidence rates in each year was statistically significant ( χ2=29.326, P<0.001). The proportion of re-treated patients (64.8%) was higher than that of newly treated patients (35.2%, χ2=50.593, P<0.001). The registered incidence rate in males (0.91/100 000) was higher than that in females (0.24/100 000, χ2=80.566, P<0.001). The age distribution showed that the highest incidence rate was in the age group≥60 years (0.96/100 000) and the lowest was in the age group 0-<45 years (0.31/100 000, χ2=55.853, P<0.001). From 2012 to 2020, Baoying County had the largest number of registered RR-PTB patients (44 cases), and its registered incidence rate (0.64/100 000) was only lower than that of Guangling District (0.98/100 000). The registered incidence rate of RR-PTB patients in Baoying County during 2016—2020 also increased significantly compared to 2012—2015 ( P=0.001). Logistic regression was used to analyze the factors related to the treatment outcome of RR-PTB patients. The results showed that patients aged≥60 years and those classified as the re-treatment were risk factors for successful treatment of RR-PTB patients ( P<0.05). In summary, males, people aged≥60 years, patients classified as the re-treatment, and residents of Baoying County should be the key populations for RR-PTB epidemic prevention and control in Yangzhou City.

Background and objective Tumor microenvironment(TME)is one of the important factors in tu-morigenesis and progression,in which tumor-associated macrophages(TAMs)play an important role in non-small cell lung cancer(NSCLC)progression.However,the mechanism of TAMs in NSCLC progression remains unclear,so this study aimed to investigate the role of TAMs in NSCLC progression and to find potential therapeutic targets.Methods Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the expression of prostaglandin E2 receptor 4(EP4)mRNA in NSCLC and normal lung tissues;the protein expression levels of cyclooxygenase-2(COX-2),EP4,cluster of differentiation 86(CD86),CD163 and CD31 were detected by immunohistochemistry(IHC)in 120 NSCLC tissues and 24 paracancerous tissues specimens.The nude mouse lung adenocarcinoma cell A549 and macrophage RAW264.7 co-transplanted tumor model was established.And the samples were collected by gavage with EP4 inhibitor E7046,and then stained with hematoxylin-eosin(HE),IHC,and immunofluorescence(IF),and then detected by Western blot for the epithelial mesenchymal transformation(EMT)of the tumor tissues of the nude mice in each group.Western blot was used to detect the expressions of EMT related protiens in each group of nude mice;full-length transcriptome sequencing was used to screen the key genes causing liver me-tastasis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results EP4 mRNA expression level in NSCLC tissues was generally lower than that in normal lung tissues(P<0.05);COX-2,EP4,CD163,CD31 proteins were differentially expressed in NSCLC tissues and adjacent tissues,and differences were observed in many clinico-pathological parameters of NSCLC patients;RAW264.7 shortened the latency period of tumorigenesis of A549 and promoted the proliferation of tumors and liver metastasis of tumors,and E7046 could reduce tumor cell proliferation activity,tumor tissue vascular density and M2-type macrophage infiltration in nude mice;IF staining showed that macrophages were mainly distributed around the metastatic foci of tumors;Western blot results showed that compared with A549 alone transplantation group,the relative expression of E-cadherin protein in tumor tissues of mice in A549 and RAW264.7 co-transplantation group was significantly decreased,and the difference was statistically significant(P<0.05),while the relative expression of N-cadherin protein was up-regulated,but the difference was not statistically significant(P>0.05);the main pathways enriched in the differ-ential genes of the full-length transcriptome were the PI3K-AKT and MAPK signaling pathways.Conclusion During NSCLC development,the COX-2/PGE2/EP4 axis may promote tumor progression by inducing macrophage functional activation,and EP4 may be a potential new target for tumor immunotherapy.This study provides new perspectives and ideas for in-depth exploration of the mechanisms of NSCLC development,as well as a theoretical basis for the development of new therapeutic strategies for NSCLC.