Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1％formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1％formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4％to 128.8％,with the relative standard deviations(RSDs)from 0.6％to 13.5％.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.

Objective To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography(CBCT)images,and to compare and analyze the estimation re-sults.Methods A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected.The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated.Three machine learning algorithms(K-nearest neighbor,ridge regression,and decision tree)and stepwise regression were used to establish four age estimation models.The coefficient of determination,mean error,root mean square error,mean square error and mean ab-solute error were computed and compared.A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed.Results The K-nearest neighbor model(R2=0.779)and the ridge regression model(R2=0.729)outperformed stepwise regression(R2=0.617),while the decision tree model(R2=0.494)showed poor fitting.The correlation heatmap demon-strated a monotonically negative correlation between age and the parameters including pulp volume,the ratio of pulp volume to hard tissue volume,and the ratio of pulp volume to tooth volume.Con-clusion Pulp volume and pulp volume proportion are closely related to age.The application of CBCT-based machine learning methods can provide more accurate age estimation results,which lays a founda-tion for further CBCT-based deep learning dental age estimation research.

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.

Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Objective To observe and compare the changes of vertebral bone mineral density(BMD)in the early stages of spinal Mycobacterium tuberculosis infection.Methods Patients who underwent spinal surgery at Xiangya Hospital,Central South University from January 1 to December 31,2023 were continuously enrolled(spinal tuber-culosis group),based on gender matching,non-spinal tuberculosis surgical patients treated for spinal stenosis were selected as the control group.Dual-energy X-ray scans were performed on the enrolled patients,difference in verte-bral BMD between two groups of patients was compared.An animal model of spinal Mycobacterium tuberculosis in-fection(referred to as the animal model)was constructed,differences in microstructure of trabecular bone between spinal tuberculosis group and control group was compared,and the bone volume/tissue volume(BV/TV),the thickness of trabecular bone(Tb.Th),the number of trabecular bone(Tb.N),and sparse density of trabecular(Tb.Sp)were used as evaluation indexes to further analyze the bone quality differences between the diseased verte-brae and the neighboring vertebrae.Results 69 patients were included in the spinal tuberculosis group and the con-trol group,respectively.The BMD of patients in the spinal tuberculosis group(0.793[0.712,0.869]g/cm2)was lower than that of the control group(0.907[0.800,1.020]g/cm2),difference was statistically significant(P＜0.05).Microstructure of trabecular bone BV/TV([18.4±5.4]％),Tb.Th([0.124±0.010]mm)in the spinal tuberculosis group of animal model were significantly altered compared with BV/TV([22.6±3.2]％),Tb.Th([0.160±0.017]mm)in the control group(both P＜0.05).In the spinal tuberculosis group,microstructure of diseased vetebral trabecular bone BV/TV([25.5±6.7]％)and Tb.N([1.871±0.443]/mm)were significantly lower than BV/TV([26.6±6.8]％)and Tb.N([1.969±0.454]/mm)in the neighboring vertebrae,both with statistically difference(both P＜0.05).Conclusion In the early stages of spinal Mycobacterium tuberculosis infec-tion,microstructure of vertebral trabecular bone can be altered,leading to a decrease in BMD.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.