Drug clinical trials constitute a critical link in new drug development and an essential means to verify the safety and efficacy of pharmaceuticals. The protection of participants’ rights and interests and the prevention of risks directly affect the scientific ethics and social credibility of the trials. Vulnerable groups， due to restricted autonomous decision-making capacities or special social status， are more susceptible to safety risks. Children are a typical representative of vulnerable groups. Their physiological particularities， cognitive limitations， and dependence collectively epitomize the universal protection demands of vulnerable research participants. Taking children as an instance， this paper analyzes the current weak links in the protection of pediatric research participants. Integrating advanced international experience with domestic practical demands， it comprehensively identified protection risk points at every stage and constructed a multi-stakeholder collaborative mechanism for the full-process protection of pediatric research participants. This mechanism incorporated seven main entities， including drug regulatory authorities， sponsors， researchers， and ethics committees， covering the pre-trial， intra-trial， and post-trial phases to meet the requirements of full-chain and multi-dimensional protection. It provided references for the subsequent establishment of a systematic protection mechanism for vulnerable populations.

Objective:To identify tumor-infiltrating immune cells that affect the prognosis of endometrial cancer(EC)with no specific molecular profile(NSMP)subtypeand to establish an integrated prognostic model based on immune cells.Methods:Gene expression data,whole exome sequencing data,and corresponding clinical infor-mation for EC patients were obtained from the The Cancer Genome Atlas(TCGA)database.The CIBERSORTx algorithm was used to evaluate the infiltration levels of 22 types of immune cells in the tumor microenvironment.Kaplan-Meier survival analysis,along with univariate and multivariate Cox regression analyses were used to identi-fy immune cells with prognostic values.A prognostic nomogram was subsequently developed based on significant immune cells and clinicopathological parameters.Results:A total of 169 EC patients classified as NSMP subtype-swere included in this study.Among them 123 patients(72.8％)were aged＜70 years,and 152 patients(89.9％)had type Ⅰ tumors.Kaplan-Meier curves showed that the proportion of plasma cells(P＜0.001),M1 macrophages(P=0.038)and activated NK cells(P=0.01)were significantly associated with overall survival.Multivariate Cox regression analysis revealed that the proportion of activated NK cells(proportion ≥0.027:HR 0.23,95％CI 0.08-0.66,P=0.006),age(≥70 years:HR4.59,95％CI 1.80-11.70,P=0.001)and tumor stage(stage Ⅱ:HR3.87,95％CI 1.18-12.70,P=0.026;stage Ⅲ:HR 6.08,95％CI 1.69-21.87,P=0.006;Ⅳ stage:HR 10.81,95％CI 3.07-38.08,P＜0.001)are independent prognostic indicators for NSMP tumors.A nomogram model was estab-lished by combining activation of NK cells,tumor stage and patient age.Internal cross-validation showed that the integrated prognostic model exhibited good predictive ability for the overall survival rates of patients(P＜0.001).Conclusions:Elevated tumor-infiltrating activated NK cells serve as an independent prognostic indicator for NSMP-subtype EC patients.When integrated with tumor stage and age,they form a robust multivariable prognos-tic model with superior predictive power.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Over the past decade, the field of bone tumor pathology in China has made remarkable progress. These achievements are reflected not only in the innovation and standardization of diagnostic techniques, which have significantly improved diagnostic accuracy, but also in the in-depth exploration of tumor pathogenesis and the continuous refinement of treatment protocols. More than one hundred research papers on bone tumor pathology published in the Chinese Journal of Pathology stand as a testament to the relentless efforts and practical contributions of Chinese pathologists in this field. On the occasion of the Chinese Journal of Pathology′s 70th anniversary, we summarize the progress in bone tumor pathology while also looking forward to the future, aiming to promote greater advancements in this field.

Objective:To identify tumor-infiltrating immune cells that affect the prognosis of endometrial cancer(EC)with no specific molecular profile(NSMP)subtypeand to establish an integrated prognostic model based on immune cells.Methods:Gene expression data,whole exome sequencing data,and corresponding clinical infor-mation for EC patients were obtained from the The Cancer Genome Atlas(TCGA)database.The CIBERSORTx algorithm was used to evaluate the infiltration levels of 22 types of immune cells in the tumor microenvironment.Kaplan-Meier survival analysis,along with univariate and multivariate Cox regression analyses were used to identi-fy immune cells with prognostic values.A prognostic nomogram was subsequently developed based on significant immune cells and clinicopathological parameters.Results:A total of 169 EC patients classified as NSMP subtype-swere included in this study.Among them 123 patients(72.8％)were aged＜70 years,and 152 patients(89.9％)had type Ⅰ tumors.Kaplan-Meier curves showed that the proportion of plasma cells(P＜0.001),M1 macrophages(P=0.038)and activated NK cells(P=0.01)were significantly associated with overall survival.Multivariate Cox regression analysis revealed that the proportion of activated NK cells(proportion ≥0.027:HR 0.23,95％CI 0.08-0.66,P=0.006),age(≥70 years:HR4.59,95％CI 1.80-11.70,P=0.001)and tumor stage(stage Ⅱ:HR3.87,95％CI 1.18-12.70,P=0.026;stage Ⅲ:HR 6.08,95％CI 1.69-21.87,P=0.006;Ⅳ stage:HR 10.81,95％CI 3.07-38.08,P＜0.001)are independent prognostic indicators for NSMP tumors.A nomogram model was estab-lished by combining activation of NK cells,tumor stage and patient age.Internal cross-validation showed that the integrated prognostic model exhibited good predictive ability for the overall survival rates of patients(P＜0.001).Conclusions:Elevated tumor-infiltrating activated NK cells serve as an independent prognostic indicator for NSMP-subtype EC patients.When integrated with tumor stage and age,they form a robust multivariable prognos-tic model with superior predictive power.

Diabetic foot is one of the most common and serious chronic complications in diabetic patients.With the advancement of digital healthcare,digital therapy has been gradually implemented and promoted among diabetic foot patients as an emerging tool with the advantages of safety,efficiency,and intelligence that can make up for the shortcomings of traditional diabetic foot risk assessment,health education,and self-management.This study provides an overview of digital therapeutics,summarizes its application in patients with diabetic foot,and proposes relevant recommendations,aiming to provide a reference for improving the quality of life and satisfaction of patients with diabetic foot and reducing the recurrence of diabetic foot.

Time perspective therapy can reshape the time perspective of chronic disease patients,improve their psychological state,optimize behavioral patterns,and enhance self-management awareness.This article reviews the concept and theoretical basis of time perspective therapy,assessment methods of time perspective,and influencing factors of time perspective in chronic disease patients,as well as methods and effects of applying time perspective therapy in self-management.Additionally,it analyzes challenges in implementation and proposes practical recommendations,aiming to provide psychological guidance for self-management interventions in chronic disease patients.

OBJECTIVE To investigate the serotypes and antimicrobial resistance rate of clinically isolated Salmonel-la in a children's hospital in Suzhou,and to provide reference for the treatment of salmonellosis.METHOD Totally 177 strains of Salmonella isolated from Children's Hospital of Wujiang District from Jan.2021 to Dec.2023 were collected,and the results of serotypes and drug sensitivity of Salmonella were analyzed.RESULTS The male to fe-male isolation rate of Salmonella was 1.39∶1,with a median age of children infection at 1.3(0.8,2.3)years.The highest number of Salmonella strains were isolated in the month of Jun.,followed by Jul.,Aug.,Sep.,Oct.and May,collectively accounting for 82.49％of all isolates.Acute gastroenteritis was manifested in 142 cases(80.22％),with respiratory tract infections in 38 cases(21.47％)and septicemia in 7 cases(3.95％).The differ-ence in detection rates across the three years was not statistically significant(P=0.806).Salmonella Typhimuri-um was the predominant serotype,representing 54.24％of all isolates.The antimicrobial drug with the highest rate of resistance in Salmonella was ampicillin(71.35％,122/171),followed by sulfamethoxazole/metronidazole(43.60％,75/172),and ampicillin/sulbactam(30.23％,52/172),and no imipenem resistant strains were found.29.07％(50/172)of strains showed multidrug resistance.CONCLUSIONS Boys under three years of age are sus-ceptible to Salmonella infections in summer and fall in this region,with Salmonella Typhimurium being the pre-dominant serotype.Clinical attention should be paid to the characteristics of Salmonella infection and drug resist-ance,as well as the early diagnosis and rational use of antimicrobial drugs.

OBJECTIVE To investigate the serotypes and antimicrobial resistance rate of clinically isolated Salmonel-la in a children's hospital in Suzhou,and to provide reference for the treatment of salmonellosis.METHOD Totally 177 strains of Salmonella isolated from Children's Hospital of Wujiang District from Jan.2021 to Dec.2023 were collected,and the results of serotypes and drug sensitivity of Salmonella were analyzed.RESULTS The male to fe-male isolation rate of Salmonella was 1.39∶1,with a median age of children infection at 1.3(0.8,2.3)years.The highest number of Salmonella strains were isolated in the month of Jun.,followed by Jul.,Aug.,Sep.,Oct.and May,collectively accounting for 82.49％of all isolates.Acute gastroenteritis was manifested in 142 cases(80.22％),with respiratory tract infections in 38 cases(21.47％)and septicemia in 7 cases(3.95％).The differ-ence in detection rates across the three years was not statistically significant(P=0.806).Salmonella Typhimuri-um was the predominant serotype,representing 54.24％of all isolates.The antimicrobial drug with the highest rate of resistance in Salmonella was ampicillin(71.35％,122/171),followed by sulfamethoxazole/metronidazole(43.60％,75/172),and ampicillin/sulbactam(30.23％,52/172),and no imipenem resistant strains were found.29.07％(50/172)of strains showed multidrug resistance.CONCLUSIONS Boys under three years of age are sus-ceptible to Salmonella infections in summer and fall in this region,with Salmonella Typhimurium being the pre-dominant serotype.Clinical attention should be paid to the characteristics of Salmonella infection and drug resist-ance,as well as the early diagnosis and rational use of antimicrobial drugs.

Diabetic foot is one of the most common and serious chronic complications in diabetic patients.With the advancement of digital healthcare,digital therapy has been gradually implemented and promoted among diabetic foot patients as an emerging tool with the advantages of safety,efficiency,and intelligence that can make up for the shortcomings of traditional diabetic foot risk assessment,health education,and self-management.This study provides an overview of digital therapeutics,summarizes its application in patients with diabetic foot,and proposes relevant recommendations,aiming to provide a reference for improving the quality of life and satisfaction of patients with diabetic foot and reducing the recurrence of diabetic foot.