Background With China's socio-economic development, the dietary structure of Chinese residents has gradually shifted from a traditional Eastern pattern characterized by high carbohydrate intake to a relatively high-fat Western dietary model, alongside a growing burden of chronic diseases. However, dietary changes may vary across different occupational groups. Objective To analyze the long-term trends in dietary energy and three major macronutrient intake among various occupational groups aged 18-59 years in nine provinces of China from 1989 to 2018, providing a scientific basis for developing occupation-specific dietary intervention strategies. Methods Based on 11 waves of data (1989–2018) from the China Health and Nutrition Survey (CHNS), 57458 employed individuals aged 18-59 years were selected as observation subjects after applying inclusion and exclusion criteria. Joinpoint regression was used to analyze temporal trends by calculating the annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals. The analysis covered the energy supply ratio from the three major macronutrients and the proportion of the participants within the acceptable macronutrient distribution ranges (AMDR) for the total occupational population and specific occupational group. Results From 1989 to 2018, the dietary structure of the occupational population in the nine provinces gradually Westernized. The carbohydrate energy supply ratio showed a decreasing trend (AAPC=−0.77%, 95%CI: −1.00%, −0.55%, P<0.05), while the fat energy supply ratio increased (AAPC=1.42%, 95%CI: 1.07%, 1.77%, P<0.05). The protein energy supply ratio remained largely unchanged (AAPC=−0.19%, 95%CI: −0.08%, 0.46%, P>0.05), and the total energy intake declined (AAPC=−0.62%, 95%CI: −0.94%, −0.30%, P<0.05). Among the occupational groups studied, white-collar workers were the first to show characteristics of dietary Westernization. Using the AMDR as the criterion, their average fat energy supply ratio first exceeded the AMDR upper limit (30%) in 1993, and their average carbohydrate energy supply ratio first fell below the AMDR lower limit (50%) in 2006, both time points being earlier than other occupational groups. Agricultural workers lagged in this transition (their average fat energy supply ratio first reached ≥30% in 2011), but their rate of increase in the fat energy supply ratio was the fastest among all occupational groups (AAPC=1.59%, 95%CI: 0.90%, 2.30%, P<0.05; P for trend comparison between groups<0.05). The other three occupational groups (blue-collar workers, service workers, and others) generally fell between these two extremes. Taking the fat energy supply ratio as an example, their AAPCs of increase were 1.02% (95%CI: 0.73%, 1.32%, P<0.05) for blue-collar workers, 0.85% (95%CI: 0.61%, 1.09%, P<0.05) for service workers, and 0.88% (95%CI: 0.58%, 1.17%, P<0.05) for others. Conclusion From 1989 to 2018, the macronutrient structure of the occupational population aged 18-59 years in nine China provinces is gradually Westernized. The energy supply ratios of carbohydrates and proteins primarily face issues of potential inadequacy, while the fat energy supply ratio is excessively high. Furthermore, the patterns of change vary among different occupational groups. It is recommended to propose personalized dietary advice tailored to specific occupations.

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

[摘 要] 目的：评估术前血清糖类抗原19-9（CA19-9）水平在Ⅱ~Ⅲ期结直肠癌术后发生异时性腹膜转移（mPM）中的预测和预后作用。方法： 回顾性分析2019年1月至2024年1月于山东第一医科大学第一附属医院肿瘤中心收治的Ⅱ～Ⅲ期结直肠癌患者临床病理信息，包括术前CA19-9和癌胚抗原（CEA）水平。采用ROC曲线及曲线下面积（AUC）评估其诊断效能。采用单因素与多因素Logistic回归及Cox比例风险回归模型分别识别风险因素与预后因素。通过倾向性评分匹配，比较CA19-9升高组和正常组无病生存期（DFS）及无腹膜转移生存期（PMFS）差异，使用Log-rank检验进行生存分析。结果： 本研究共纳入286例患者，术前CA19-9升高与黏液腺癌组织类型（P = 0.005）、T4分期（P < 0.001）、淋巴结转移（P = 0.02）、术前CEA升高（P = 0.024）、神经侵犯（P = 0.02）、低分化程度（P = 0.045）显著相关。升高的CA19-9水平对mPM的预测准确性优于CEA（AUC：0.73，95% CI：0.61~0.85 vs AUC：0.64，95% CI：0.55~0.73）。多因素Logistic回归分析显示，术前CA19-9升高是发生mPM的独立预测因子（OR = 5.59，95% CI：2.00~15.58，P = 0.001）。CA19-9升高患者的中位DFS[54.27个月 vs 未达到（NR），HR = 3.55，95% CI：1.96~6.44，P < 0.001]与PMFS（NR vs NR，HR = 6.93，95% CI：3.25~14.76，P < 0.001）显著缩短。倾向性评分匹配后，DFS（54.27个月 vs NR，HR = 4.26，95% CI：1.40~12.98，P = 0.006）与PMFS（NR vs NR，HR = 4.28，95% CI：1.19~15.34，P = 0.015）均维持显著性差异。多因素Cox回归分析显示，针对PMFS，术前CA19-9升高是患者不良预后的独立因素（HR = 3.70，95% CI：1.55~8.83，P = 0.003）。结论： 术前血清CA19-9升高是Ⅱ～Ⅲ期结直肠癌患者术后发生mPM的敏感生物标志物，可提供独立的风险预测和预后分层。

ObjectiveTo explore the mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating metabolic hypertension induced by a high-sugar and high-fat diet in rats based on network pharmacology， proteomics， and animal experiments. MethodsThirty male SD rats were randomized into the control， model， positive drug （tetrandrine， Tet， 50 mg·kg^-1·d^-1）， low-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-L， 45×10⁴ mg·kg^-1·d^-1）， and high-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-H， 90×10⁴ mg·kg^-1·d^-1） groups. Except for the control group， each group was fed a high-fat and high-sugar diet for 8 weeks for the modeling of metabolic hypertension. Following successful modeling， drug interventions were conducted through gavage for 4 weeks. Blood pressure and lipid indicators were monitored， and cardiac function was assessed via echocardiography. Samples from the thoracic aorta and cardiac tissue were collected for histopathological examination. Network pharmacology analysis identified key active components， potential targets， and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension. Proteomics technology was employed to analyze the differential proteins and major pathway targets to synergistically elucidate the antihypertensive mechanism of Salviae Miltiorrhizae Radix et Rhizoma. Ca²⁺ concentrations in the thoracic aorta and cardiac tissue were measured. The protein levels of transient receptor potential cation channel （TRPC）3， TRPC6， NADPH oxidase （NOX）2， and NOX4 were quantified via Western blotting. The levels of oxidative stress markers and inflammatory factors， including superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β）， were determined by enzyme-linked immunosorbent assay （ELISA）. Molecular docking analysis was performed for the main components of Salviae Miltiorrhizae Radix et Rhizoma with TRPC3， TRPC6， NOX2， and NOX4. ResultsThe experimental results indicated that compared with the control group， the model group exhibited abnormally elevated blood pressure and increased lipid levels （P<0.01）. Compared with the model group， the DS-L group exhibited reduced systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and mean arterial pressure （MAP） （P<0.05）， decreased serum levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05）， and increased level of high-density lipoprotein cholesterol （HDL-C） （P<0.01）. The DS-H and Tet groups showed more significant effects （P<0.01）. Moreover， the interventions attenuated vascular wall thickening， myocardial cell injury， and collagen and lipid deposition. Network pharmacology and proteomics prediction results indicated that the core targets of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension were TRPC3， TRPC6， NOX2， and NOX4， and the core pathways included calcium signaling， cyclic guanosine monophosphate （cGMP）/cGMP-dependent protein kinase （PKG） signaling， and atherosclerosis-related pathways. The molecular mechanism experiment results indicated that compared with the control group， the model group exhibited significantly elevated tissue Ca²⁺ concentrations， exacerbated oxidative stress and inflammatory responses， and upregulated protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.01）. Compared with the model group， DS-L reduced the free Ca²⁺ concentration， lowered the levels of IL-1β， TNF-α， SOD， and MDA （P<0.05）， and downregulated the protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.05）. DS-H and Tet exhibited more significant effects （P<0.01）. Meanwhile， the main components of Salviae Miltiorrhizae Radix et Rhizoma had strong binding affinity with the core targets of hypertension. ConclusionSalviae Miltiorrhizae Radix et Rhizoma may ameliorate oxidative stress and mitigate inflammatory responses by regulating the TRPC3/6/NOX2/4 signaling pathway， thereby alleviating abnormal blood pressure abnormality and myocardial injury in hypertensive rats.

ObjectiveTo evaluate the effects of Qingre Huoxue prescription combined with methotrexate （MTX） and folic acid （FA） on homocysteine （Hcy） levels and disease activity in patients with rheumatoid arthritis （RA） complicated by hyperhomocysteinemia （HHcy）. MethodsOn the basis of a multicenter real-world cohort from the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform，408 patients with RA complicated by HHcy were selected and included in this study. Treatment with Qingre Huoxue prescription was used as the exposure factor. According to whether Qingre Huoxue prescription was combined with MTX and FA，patients were assigned into an exposure group of 281 cases and a control group of 127 cases. Follow-ups were conducted every three months，with the primary outcome indicator being the achievement rate of target Hcy level. A generalized estimating equation model was adopted to analyze the dynamic changes in Hcy level under different medication regimens. Kaplan-Meier analysis was performed to evaluate the cumulative achievement rate of target Hcy level in the two groups，and Cox regression analysis was conducted to explore the predictive factors affecting the achievement rate of target Hcy level. Changes in erythrocyte sedimentation rate （ESR），C-reactive protein （CRP），28-joint disease activity score （DAS 28），and Health Assessment Questionnaire-Disability Index （HAQ-DI） scores before and after the first combined treatment with Qingre Huoxue prescription were compared between the two groups. ResultsThe Hcy level in the exposure group showed a gradual decreasing trend over time，while the decrease in Hcy level was not significant in the control group. At the 12-month follow-up，the achievement rate of target Hcy level in the exposure group （124/281，44.13%） was higher than that in the control group （23/127，18.11%，P<0.01）. Multivariable Cox regression analysis showed that treatment with Qingre Huoxue prescription ［hazard ratio（HR）=3.013，95% confidence interval （CI） 2.188-4.149， P<0.001］， absence of comorbidities （HR=2.035， 95%CI 1.352-3.061， P<0.001）， and baseline Hcy <15 μmol·L^-1 （HR=1.810， 95%CI 1.390-2.357， P<0.001） were significantly associated with an increased likelihood of achieving target Hcy levels within 6 months. In contrast， higher PGA scores were associated with a reduced likelihood of achieving target Hcy levels （HR=0.991， 95% CI 0.986-0.997， P=0.003）. After treatment，the exposure group demonstrated reductions in ESR，CRP，and DAS 28 scores （P<0.05） and had lower ESR，CRP and DAS 28 scores than the control group （P<0.05）. ConclusionEven after taking FA supplements，some RA patients undergoing MTX treatment still have high Hcy levels. When being used in conjunction with MTX and FA，Qingre Huoxue prescription can effectively lower the Hcy level and disease activity in RA patients with HHcy，outperforming Western treatment alone.

ObjectiveTo evaluate the effects of Qingre Huoxue prescription combined with methotrexate （MTX） and folic acid （FA） on homocysteine （Hcy） levels and disease activity in patients with rheumatoid arthritis （RA） complicated by hyperhomocysteinemia （HHcy）. MethodsOn the basis of a multicenter real-world cohort from the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform，408 patients with RA complicated by HHcy were selected and included in this study. Treatment with Qingre Huoxue prescription was used as the exposure factor. According to whether Qingre Huoxue prescription was combined with MTX and FA，patients were assigned into an exposure group of 281 cases and a control group of 127 cases. Follow-ups were conducted every three months，with the primary outcome indicator being the achievement rate of target Hcy level. A generalized estimating equation model was adopted to analyze the dynamic changes in Hcy level under different medication regimens. Kaplan-Meier analysis was performed to evaluate the cumulative achievement rate of target Hcy level in the two groups，and Cox regression analysis was conducted to explore the predictive factors affecting the achievement rate of target Hcy level. Changes in erythrocyte sedimentation rate （ESR），C-reactive protein （CRP），28-joint disease activity score （DAS 28），and Health Assessment Questionnaire-Disability Index （HAQ-DI） scores before and after the first combined treatment with Qingre Huoxue prescription were compared between the two groups. ResultsThe Hcy level in the exposure group showed a gradual decreasing trend over time，while the decrease in Hcy level was not significant in the control group. At the 12-month follow-up，the achievement rate of target Hcy level in the exposure group （124/281，44.13%） was higher than that in the control group （23/127，18.11%，P<0.01）. Multivariable Cox regression analysis showed that treatment with Qingre Huoxue prescription ［hazard ratio（HR）=3.013，95% confidence interval （CI） 2.188-4.149， P<0.001］， absence of comorbidities （HR=2.035， 95%CI 1.352-3.061， P<0.001）， and baseline Hcy <15 μmol·L^-1 （HR=1.810， 95%CI 1.390-2.357， P<0.001） were significantly associated with an increased likelihood of achieving target Hcy levels within 6 months. In contrast， higher PGA scores were associated with a reduced likelihood of achieving target Hcy levels （HR=0.991， 95% CI 0.986-0.997， P=0.003）. After treatment，the exposure group demonstrated reductions in ESR，CRP，and DAS 28 scores （P<0.05） and had lower ESR，CRP and DAS 28 scores than the control group （P<0.05）. ConclusionEven after taking FA supplements，some RA patients undergoing MTX treatment still have high Hcy levels. When being used in conjunction with MTX and FA，Qingre Huoxue prescription can effectively lower the Hcy level and disease activity in RA patients with HHcy，outperforming Western treatment alone.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Objective:To establish a linear calibration method using two reference substances for seven characteristic peaks of Cassiae Semen under complicated chromatographic condition,and to optimize the method.Methods:Using 15 different types of screened chromatographic columns and 2 components as reference compounds pair,the linear calibration method with 2 reference substances was established to predict the retention time of the other 5 components,and the method was verified by unknown chromatographic columns and unknown samples.Combined with column confirmation number and average coincidence rate of target peaks,the location results were compared comprehen-sively,and the method was optimized according to the defect under the influence of complicated chromatographic condition.Results:The average conformity rate of the target peak of the method before optimization was 73.3％,and the average conformity rate of the target peak of the optimized method was 98.7％.The optimized method has a high-er average peak coincidence rate and a wider range of applicability for the chromatographic column.Conclusion:The optimized linear calibration method using two reference substances can assist the localization analysis of chromato-graphic peaks in the characteristic chromatogram under complicated chromatographic condition.

Objective To investigate the expression of arginase Ⅱ(ArgⅡ)in kidney tissue of rats with diabetic nephropathy(DN)and its significance in the development of DN.Methods A total of 10 male SD rats were randomly divided into the control group and the model group,with 5 rats in each group.An rat model of DN was developed by feeding with high-sugar and high-fat diet combined with intra-peritoneal injection of low-dose streptozotocin(45 mg/kg),and they were sacrificed after 11 weeks of continued feeding.The body weight,and biochemical indexes of blood and urine of rats were determined.The right kidney was weighed and histopathological examination was performed.The pathological changes of kidney tissues and protein expression of ArgⅡ and CD68+were observed,and the immunofluores-cence double staining was used to observe the distribution and expression of ArgⅡand a marker of renal macrophage activation CD68+;the protein expression of ArgⅡ,NF-κB,TNF-α and IL-6 in kidney tissues was determined by Western blot.Results Compared with the control group,the ratio of kidney weight to body weight,24-hour urine volume,24-hour urine protein,fasting blood glucose,urea nitrogen and insulin level in the model group were significantly increased(P<0.05).The renal histopathology showed that the mesangial cells of the renal glomerular were necrotic with vascular dilatation,and the renal tubular epithelial cells were steatosis and congestion.Compared with the control group,the protein expression of ArgⅡ,CD68+,NF-κB,TNF-α and IL-6 in the kidney tissues of the model group were significantly increased(P<0.05).Immunofluorescence double staining demonstrated the co-expression of ArgⅡ and CD68+in renal tissue,and the fluorescence intensities of both ArgⅡ and CD68+in the model group were significantly stronger than those in the control group(P<0.01).Conclusion The expression of ArgⅡ is increased in DN,which may be participated in the occurrence of inflammatory lesions in DN.

Objective:To compare bowel function 12 months after surgery between side-to-end anastomosis (SEA) and end-to-end anastomosis (EEA) groups of patients who had undergone rectal cancer resection.Methods:This single-center, prospective, open-label, phase III randomized controlled trial was approved by the Ethics Committee of Peking University People's Hospital (2018PHB040-01) and registered at ClinicalTrials. org (NCT03669237). Inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor located 0 to 12 cm from the anal verge; (3) age≥18 years; and (4) planned R0 resection with primary reconstruction. Exclusion criteria included: (1) emergency surgery; (2) cognitive impairment; (3) non-primary anastomosis; (4) history of left-sided colonic or anorectal surgery; and (5) preexisting chronic defecation dysfunction. Eligible rectal cancer patients scheduled for elective sphincter-preserving surgery at Peking University People's Hospital were prospectively enrolled between October 2018 and March 2021 and randomly assigned to either the EEA group or the SEA group via computer-generated numbers prior to entering the operating room. All patients underwent standard radical tumor resection. Bowel function was evaluated by the low anterior resection syndrome (LARS) questionnaire. It consists of five single-choice questions and yields a total score ranging from 0 to 42. Defecation function is categorized into three levels: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The primary endpoint was the LARS score 12 months after surgery. Secondary endpoints included LARS scores from 1 to 11 months and during long-term follow-up(>12 months). The final follow-up was completed in July 2022. All randomized patients were included in the intention-to-treat set (ITTS). The full analysis set (FAS) was defined as ITTS patients with valid outcome data. All primary statistical analyses were performed in the FAS, and results were further compared in the per-protocol set (PPS) based on the actual treatment received.Results:A total of 323 patients underwent eligibility assessment, of whom 71 did not meet the inclusion criteria and 52 declined to participate. Ultimately, 200 patients were randomized. Median age was 64 years and 85 were women. The SEA and EEA groups comprised 102 and 98 patients, respectively. A total of 181 patients (90.5%) were included in the FAS, and 170 (85.0%) were included in the PPS. Among these, the 12-month LARS score was evaluated in 178 patients (98.3%) in the FAS and in 167 (98.2%) in the PPS. Median LARS score at 1–12 months were significantly lower in the SEA group in both the FAS dataset [12 months:8 (interquartile range [IQR], 0–22) vs. 14 (IQR, 8–29); Z=2.687, P=0.007] and the PPS dataset [12 months: 8 (IQR, 0–22) vs. 14 (IQR, 6–29); Z=2.543, P=0.011]. During long-term follow-up, the median LARS score was also significantly lower in the SEA group in the FAS dataset [2 (IQR, 0–4) vs. 11 (IQR, 2–23); Z=2.968, P=0.003] and the PPS dataset [2 (IQR, 0–14) vs. 11 (2, 27); Z=2.687, P=0.007]. Conclusion:Compared with the EEA group, bowel function was superior in the SEA group 1 year after surgery and during long-term follow-up.