[摘 要] 目的：探究银杏内酯B（GKB）调控蛋白激酶R样内质网激酶（PERK）/转录激活子4（ATF4）/C/EBP同源蛋白（CHOP）信号通路对肝癌细胞增殖、迁移、凋亡和上皮间质转化（EMT）的影响。方法：将人肝癌细胞MHCC-97H随机分为对照组、GKB组、GSK2656157（PERK抑制剂）组和GKB + GSK2656157组，以GKB和GSK2656157分别干预后，采用MTT法和EdU染色检测各组细胞的增殖活性及增殖率，划痕愈合实验、流式细胞术分别检测各组细胞的迁移及凋亡水平，WB法检测各组细胞中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。构建MHCC-97H细胞裸鼠移植瘤模型，以同法分组及药物干预后测定各组移植瘤体积，采用免疫组化、TUNEL染色分别检测各组肿瘤细胞增殖、凋亡水平，WB法检测各组移植瘤组织中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。结果：与对照组比较，GKB组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著降低（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著升高（均P < 0.05）；GSK2656157组各指标变化与GKB组相反（均P < 0.05）。与GKB组比较，GKB + GSK2656157组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著升高（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著降低（均P < 0.05）。结论：GKB可通过激活PERK/ATF4/CHOP信号通路抑制肝癌MHCC-97H细胞增殖、迁移和EMT并促进其凋亡。

Fresh-cut processing constitutes a pivotal technique in the origin processing of Chinese medicinal materials， with a long history documented in multiple materia medica. In recent years， it has garnered national policy support for its ability to prevent component loss and low processing efficiency associated with traditional drying-before-cutting methods. As of August 2025， 26 provinces and municipalities nationwide have cumulatively published 789 species for fresh-cut processing. Among these， 78 were included in the 2025 edition of the Pharmacopoeia of the People's Republic of China. However， the practice continues to face common challenges and difficulties， including ambiguous scientific understanding， fragmented standards， limited quality control approaches， and poor process stability. Based on this， this paper synthesises years of research findings to systematically elucidate the core mechanisms of fresh-cut processing. These encompass alterations to herbal tissue structure during cutting， post-processing changes in constituents， and physiological-biochemical processes such as plant stress responses and shifts in endogenous enzyme activity. It also summarises influencing factors， including inherent herbal properties， cutting timing and methods， and environmental conditions like temperature， humidity， and microbial presence. Based on this overview of fresh-cutting mechanisms， subsequent research should advance in four directions：Clarifying the scientific principles of fresh-cutting， overcoming technical bottlenecks， upgrading intelligent equipment， and establishing quality standards and evaluation systems. This study provides a theoretical foundation and scientific basis for future research on fresh-cutting in traditional Chinese medicine（TCM）， promoting its deeper practical application within the industry and contributing to the high-quality development of TCM industry and the modernization of TCM.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective: To explore the correlation between parent-child separation experience and non suicidal self injury (NSSI) behavior among junior and senior high school students, so as to provide a reference for the prevention and improvement of NSSI behavior among junior and senior high school students. Methods: Using a stratified cluster random sampling method, 3 114 junior and senior high school students aged 11-19 years were recruited from Chenzhou and Jishou cities in Hunan Province between November 2024 and September 2025. A self designed questionnaire and the Functional Self injury Behavior Assessment Scale were used to collect information on parental labor migration and adolescents NSSI behavior status. Binary Logistic regression model was used to analyse the association between parent-child separation experiences and NSSI behavior among junior and senior high school students, with further stratified analysis by gender. Results: The prevalence rate of NSSI behavior among junior and senior high school students was 9.9%, and the overall incidence of parent-child separation was 48.9%, comprising 17.1% separated from their father only, 5.5% separated from their mother only, and 26.3% separated from both parents. After adjusting for variables such as age, gender, and ethnicity, the results of binary Logistic regression analyses indicated that adolescents with parent-child separation experiences had a higher risk of NSSI behavior ( OR =1.31, 95% CI =1.01-1.69, P <0.05). Compared with those without parent-child separation experiences, adolescents who were separated from their mother only ( OR =1.68, 95% CI =1.03-2.74) or from both parents ( OR =1.41, 95% CI =1.04-1.92) showed significantly increased risks of NSSI behavior (both P <0.05). Conclusions Parent-child separation experiences are associated with an increased risk of NSSI behavior among junior and senior high school students. Strengthened attention should be paid to left behind senior high school students to reduce the occurrence of NSSI in adolescents.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.