Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective:To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019.Methods:Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method.Results:The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively ( P＜0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively ( P＜0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions:Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

Objective To explore the potential characteristics of self-management behavior in maintenance hemodialysis patients with hypertension and determine the influencing factors of different characteristics,so as to provide reference for improving self-management behavior.Methods A total of 192 maintenance hemodialysis patients with hypertension who received dialysis in The First Hospital Affiliated to Naval Medical University from May to September 2022 were enrolled by convenience sampling.A general information questionnaire,hypertension self-management behavior scale,Morisky medication adherence scale-8 items,and medication adherence self-efficacy scale-revision(MASES-R)were used to investigate the potential categories of self-management behavior in maintenance hemodialysis patients with hypertension,and the predictive indicators of each category were analyzed by latent profile analysis.Results Three latent categories of self-management behavior in maintenance hemodialysis patients with hypertension were identified:low self-management behavior,moderate self-management behavior,and high self-management behavior.Medication adherence and medication adherence self-efficacy were predictors of high self-management behavior.Monitoring blood pressure once daily was a predictor of moderate self-management behavior.Conclusion There is significant self-management characteristics among maintenance hemodialysis patients with hypertension.These characteristics and risk factors should be identified early to help patients improving their self-management.

Objective:To analyze Chinese and English literature related to Kangfuxin liquid for wound healing using CiteSpace Knowledge Graph,and to understand its research hotspots,current status,and development trend.Methods:Chinese literature on Kangfuxin Liquid in promoting wound healing was retrieved from the China National Knowledge Infrastructure(CNKI),and English literature from Web of Science(WOS),covering the period from January 1,2004,to October 1,2024.CiteSpace 6.1.R6 was used to perform visual analyses based on publication volume,institutions,authors,and keywords.Results:A total of 795 Chinese articles and 21 English articles were included.Overall publication volumes for both languages showed an upward trend,though Chinese publications slightly declined after 2017.Author collaboration network analysis revealed scattered and limited cooperation among researchers,with the field predominantly led by domestic scholars.Institutional collaboration analysis identified Chengdu University of Traditional Chinese Medicine as the most prolific institution in both Chinese and English literature.The mapping indicated closer collaboration among English literature institutions compared to Chinese counterparts.High-frequency keywords in Chinese literature included Kangfuxin liquid,pressure ulcer,and wound healing,while English keywords included expression,chitosan,and induced gastric ulcer.The representative clustering tags in the Chinese database were#0 Kangfuxin,#1 nurse,and#2 therapeutic effect.The representative English clustering tags were#0 diabetic wound,#1 marine polysaccharide,and#2 slamf 9.The research hotspot of the Chinese database before 2019 focused on Kangfuxin Liquid's role in wound healing,while post-2020 studies shifted toward the role of inflammatory factors during healing.Conclusions:Visual analysis confirms Kangfuxin Liquid in wound healing as a research hotspot.Future studies should strengthen interdisciplinary and regional collaborations,with mechanistic exploration and clinical applications prioritized.

Objectives:This study aimed to compare the disease-free survival(DFS)and cervical lymph node metastasis risk in lip squamous cell carinoma(LSCC)patients between microwave thermochemotherapy and traditional surgical resection.Methods:A retrospective analysis was conducted on 106 eligible LSCC patients treated between January 2010 and January 2022.Patients were divided into the microwave thermochemotherapy group(n=37)and the surgery-alone group(n=69).Survival curves were generated using the Kaplan-Meier method,with DFS differences evaluated by Log-Rank test.Cox proportional hazards models and logistic re-gression were employed to screen prognostic factors and assess variables associated with cervical lymph node metastasis,respective-ly.Statistical analyses were performed using SPSS 26.0.Results:By September 2024,the objective response rate in the microwave thermochemotherapy group reached 94.59％(35/37).Survival analysis revealed no statistically significant difference in DFS be-tween the two groups(P=0.300).Multivariate logistic regression demonstrated that treatment modality was associated with cervical lymph node metastasis risk(P=0.022).The microwave thermochemotherapy group exhibiting a trend toward lower cervical lymph node metastasis rates compared to the surgery group.Conclusion:This study suggests that microwave thermochemotherapy achieves disease control efficacy comparable to surgical resection in early-stage LSCC patients and may reduce the likelihood of regional lymph node metastasis.

Objective:To analyze Chinese and English literature related to Kangfuxin liquid for wound healing using CiteSpace Knowledge Graph,and to understand its research hotspots,current status,and development trend.Methods:Chinese literature on Kangfuxin Liquid in promoting wound healing was retrieved from the China National Knowledge Infrastructure(CNKI),and English literature from Web of Science(WOS),covering the period from January 1,2004,to October 1,2024.CiteSpace 6.1.R6 was used to perform visual analyses based on publication volume,institutions,authors,and keywords.Results:A total of 795 Chinese articles and 21 English articles were included.Overall publication volumes for both languages showed an upward trend,though Chinese publications slightly declined after 2017.Author collaboration network analysis revealed scattered and limited cooperation among researchers,with the field predominantly led by domestic scholars.Institutional collaboration analysis identified Chengdu University of Traditional Chinese Medicine as the most prolific institution in both Chinese and English literature.The mapping indicated closer collaboration among English literature institutions compared to Chinese counterparts.High-frequency keywords in Chinese literature included Kangfuxin liquid,pressure ulcer,and wound healing,while English keywords included expression,chitosan,and induced gastric ulcer.The representative clustering tags in the Chinese database were#0 Kangfuxin,#1 nurse,and#2 therapeutic effect.The representative English clustering tags were#0 diabetic wound,#1 marine polysaccharide,and#2 slamf 9.The research hotspot of the Chinese database before 2019 focused on Kangfuxin Liquid's role in wound healing,while post-2020 studies shifted toward the role of inflammatory factors during healing.Conclusions:Visual analysis confirms Kangfuxin Liquid in wound healing as a research hotspot.Future studies should strengthen interdisciplinary and regional collaborations,with mechanistic exploration and clinical applications prioritized.

Objectives:This study aimed to compare the disease-free survival(DFS)and cervical lymph node metastasis risk in lip squamous cell carinoma(LSCC)patients between microwave thermochemotherapy and traditional surgical resection.Methods:A retrospective analysis was conducted on 106 eligible LSCC patients treated between January 2010 and January 2022.Patients were divided into the microwave thermochemotherapy group(n=37)and the surgery-alone group(n=69).Survival curves were generated using the Kaplan-Meier method,with DFS differences evaluated by Log-Rank test.Cox proportional hazards models and logistic re-gression were employed to screen prognostic factors and assess variables associated with cervical lymph node metastasis,respective-ly.Statistical analyses were performed using SPSS 26.0.Results:By September 2024,the objective response rate in the microwave thermochemotherapy group reached 94.59％(35/37).Survival analysis revealed no statistically significant difference in DFS be-tween the two groups(P=0.300).Multivariate logistic regression demonstrated that treatment modality was associated with cervical lymph node metastasis risk(P=0.022).The microwave thermochemotherapy group exhibiting a trend toward lower cervical lymph node metastasis rates compared to the surgery group.Conclusion:This study suggests that microwave thermochemotherapy achieves disease control efficacy comparable to surgical resection in early-stage LSCC patients and may reduce the likelihood of regional lymph node metastasis.

Objective:To assess any effect of combining kinesio taping with Baduanjin in the management of upper cross syndrome (UCS).Methods:Thirty-nine college students with UCS were randomly divided into a kinesio taping group ( n=14), a Baduanjin group ( n=12) and a combined treatment group ( n=13). The kinesio taping and Baduanjin groups received taping and underwent Baduanjin training, respectively, while the combined treatment group received both interventions for 6 weeks. Before, as well as 3 and 6 weeks after the intervention, all were evaluated using a visual analogue scale (VAS), a neck disability index (NDI), and for forward head extension (FHA), round shoulder angle (FSA) and vital capacity (VC). Results:A significant decrease in the average VAS ratings and NDI scores, and better average FHA and FSA was observed in both groups after the experiment. There was also a significant increase in VC. At 6 weeks, all of the indicators were significantly better than three weeks earlier. The kinesio taping and Baduanjin groups showed significantly smaller average improvements than the combined group.Conclusions:Kinesio taping combined with Baduanjin can effectively alleviate pain associated with UCS, relieve cervical dysfunction, correct abnormal posture and increase lung capacity. Its efficacy is superior to that achieved through single interventions.

Objective:To assess any effect of combining kinesio taping with Baduanjin in the management of upper cross syndrome (UCS).Methods:Thirty-nine college students with UCS were randomly divided into a kinesio taping group ( n=14), a Baduanjin group ( n=12) and a combined treatment group ( n=13). The kinesio taping and Baduanjin groups received taping and underwent Baduanjin training, respectively, while the combined treatment group received both interventions for 6 weeks. Before, as well as 3 and 6 weeks after the intervention, all were evaluated using a visual analogue scale (VAS), a neck disability index (NDI), and for forward head extension (FHA), round shoulder angle (FSA) and vital capacity (VC). Results:A significant decrease in the average VAS ratings and NDI scores, and better average FHA and FSA was observed in both groups after the experiment. There was also a significant increase in VC. At 6 weeks, all of the indicators were significantly better than three weeks earlier. The kinesio taping and Baduanjin groups showed significantly smaller average improvements than the combined group.Conclusions:Kinesio taping combined with Baduanjin can effectively alleviate pain associated with UCS, relieve cervical dysfunction, correct abnormal posture and increase lung capacity. Its efficacy is superior to that achieved through single interventions.