ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Objective: To investigate the efficacy，safety and feasibility of regional lymph node dissection in laparoscopic radical surgery for bladder cancer under the guidance of indocyanine green fluorescence imaging. Methods: A total of 30 patients with muscle invasive bladder cancer (T2/T3NxM0) who volunteered to enter the clinical trial were randomly divided into the indocyanine green imaging guided laparoscopic regional lymph node dissection group (n=15) and the standard pelvic lymph node dissection group (n=15).The number of positive lymph nodes，operation time，intraoperative bleeding volume，incidence of lymph leakage，and tumor recurrence and metastasis rate 2-year after surgery were collected. Results: The number of positive lymph nodes was (4.20±1.66) and (4.60±1.72) respectively in the indocyanine green and standard groups，with no statistically significant difference (P>0.05).There were no statistically significant difference in the tumor recurrence and metastasis rates 2-year after surgery between the two groups (P>0.05).However，the indocyanine green group had shorter operation time，less intraoperative bleeding volume，and lower incidence of lymphatic leakage than the standard group (P<0.05). Conclusion: Indocyanine green fluorescence imaging guided laparoscopic lymph node dissection has comparable clinical efficacy to standard lymph node dissection，but with fewer complications.

Objective: To investigate the prevalence and influencing factors of depression among middle school students in Jiading District, Shanghai Municipality, so as to provide the evidence for developing mental health intervention strategies among middle school students. Methods: Students from 3 junior high schools and 3 senior high schools in Jiading District were selected from June 2022 to June 2023 using a stratified random cluster sampling method. Basic information including gender and educational stage was collected through questionnaire surveys. Depression, mental health literacy, cognitive emotion regulation, family cohesion, school climate, stress, and life satisfaction were assessed using the Children's Depression Inventory, the Mental Health Literacy Assessment Scale, the Chinese version of the Cognitive Emotion Regulation Questionnaire, the Family Adaptability and Cohesion Scale, the Perceived School Climate Scale, Depression-Anxiety-Stress Scale, and the Life Satisfaction Scale, respectively. Factors affecting depression among middle school students were analyzed using a multivariable logistic regression model. Results: There were 1 117 boys (53.94%) and 954 girls (46.06%), with a mean age of (15.20±1.77) years. There were 1 193 (57.61%) junior high school students and 878 (42.39%) senior high school students. Depression was detected in 577 students, with a prevalence of 27.86%. Multivariable logistic regression analysis identified gender (boy, OR=0.652, 95%CI: 0.512-0.832), educational stage (senior high school, OR=2.519, 95%CI: 1.584-4.008), mental health literacy (OR=0.958, 95%CI: 0.951-0.966), cognitive emotion regulation (adaptive cognitive emotion regulation strategies, OR=0.970, 95%CI: 0.958-0.982; maladaptive cognitive emotion regulation strategies, OR=1.103, 95%CI: 1.084-1.123), family cohesion (OR=0.910, 95%CI: 0.899-0.921), school climate (OR=0.720, 95%CI: 0.694-0.747), stress (OR=1.127, 95%CI: 1.104-1.150), life satisfaction (OR=0.817, 95%CI: 0.799-0.836) as factors affecting depression among middle school students. Conclusions Depression among middle school students in Jiading District is associated with gender, educational stage, mental health literacy, cognitive emotion regulation, family cohesion, school climate, stress, and life satisfaction. It is recommended that targeted measures be taken from the perspectives of individuals, families, schools, and society to promote the mental health of middle school students.

Objective To investigate the efficacy,safety and feasibility of laparoscopic lymph node dissection guided by indocyanine green(ICG)fluorescence imaging.Methods A total of 30 patients with muscle-invasive bladder cancer(MIBC,T2/T3NxM0)who were admitled to the Cangzhou People's Hospital during Mar.2018 and Jun.2022 were included.The lymph nodes were cleared with ICG fluorescence imaging first,and then the remaining lymph nodes were cleared according to the standard pelvic lymph node range.The lymph node positive rate of ICG fluorescence imaging guided laparoscopic lymph node precise dissection and standard pelvic lymph node dissection was analyzed by self-comparison.Results ICG fluorescence imaging guided laparoscopic lymph node precise dissection needed shorter operation time than standard pelvic lymph node dissection[(21.80±6.80)min vs.(47.70±10.73)min,P＜0.05].There was no significant difference in the lymph node positive rate between the two approaches[(11.34±9.06)％vs.(12.36±9.43)％,P＞0.05],but the former approach caused less damage on blood vessels and nerves.Conclusion Indocyanine green fluorescence imaging guided laparoscopic lymph node dissection has comparable efficacy to standard pelvic lymph node dissection,which can reduce ineffective lymph node dissection,shorten the operation time,and reduce the risk of complications.

Objective:To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds.Methods:Clinical data of 38 patients with large limb surface wound(11 cm×39 cm-16 cm×65 cm)admitted to the Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed.Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap(ALTP-SCIAP)with turbocharge technique(interregional flap group);while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps,combined with skin grafting if necessary(traditional anterolateral femoral flap group).The survival of skin flap,repair of donor area,complications and patient satisfaction were compared between the two groups.Results:In interregional flap group,18 flaps were harvested and transplanted,the flap width,length and the viable area were(9.9±2.0)cm,(44.2±3.5)cm and(343.2±79.9)cm2,respectively.In traditional anterolateral femoral flap group,29 flaps were harvested and transplanted,the flap width,length and the viable area were(11.0±2.8)cm,(21.7±3.2)cm and(186.4±49.2)cm2,respectively.There were significant differences in the flap length and the viable area between the two groups(t=22.365 and 8.345,both P<0.05).In the interregional flap group,the donor site of flap was closed by direct suture in 11 flaps,by skin retractor assisted suture in 6 flaps,and by skin grafting in one flap.In traditional anterolateral femoral flap group,the donor site of flap was closed by direct suture in 12 flaps,by skin retractor assisted suture in 11 flaps,and by skin grafting in 6 flaps.The skin graft rates of the two groups were 5.6%(1/18)and 20.7%(6/29),respectively(χ2=2.007,P>0.05).The interregional flap group had lower postoperative complications rate(5.6%vs.35.0%,χ2=4.942,P<0.05)and higher patient satisfaction rate(94.4%vs.70.0%,χ2=4.448,P<0.05)than traditional anterolateral femoral flap group.Conclusion:Compared with the traditional anterolateral femoral flap,the anterolateral femoral interregional flap with turbocharge technique has a larger flap area,most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.

Objective To investigate the causal relationship between walking pace(WP)with interver-tebral disc degeneration(IVDD)and low back pain(LBP)by using two-sample Mendelian randomisation(MR)analysis method.Methods A genome-wide association study database of WP,IVDD and LBP was ob-tained,and single nucleotide polymorphisms(SNP)strongly associated with exposure were obtained as the in-strumental variables.The two confounders of smoking and sedentary were conservatively removed,and the MR analyses were performed by inverse variance weighting(IVW),weighted median,and MR-Egger methods to assess the causal relationship between WP with IVDD and LBP.The consistency and accuracy of results were ensured by heterogeneity,diversity tests,MR-PRESSO and negative control.Results The I VW results showed a significant negative correlation between WP and IVDD(OR=0.348,95％CI:0.183-0.661,P=0.001)and vice versa(OR=0.972,95％CI:0.953-0.992,P=0.007).Meanwhile there was also a significant negative correlation between WP and LBP(OR=0.214,95％CI:0.119-0.385,P＜0.001),but no causal re-lationship was found between LBP and WP.Conclusion Faster WP could effectively prevent the occurrence of IVDD and LBP,and IVDD may contribute to the occurrence of slow walking.

Objective To investigate the expression significance and prognostic value of long non-coding RNA tumor susceptibility candidate gene 9(lncRNA CASC9)and YKT6 in oral squamous cell carcinoma(OSCC).Methods A total of 110 patients with OSCC treated in the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from January 2016 to January 2018 were selected as the study objects.The mRNA expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue and adjacent tissues was detected by real-time fluorescence quantitative PCR.Immunohistochemistry was used to detect YKT6 protein expression in OSCC cancer tissue and adjacent tissues.Kaplan-Meier curves were used to analyze the influence of different lncRNA CASC9 and YKT6 mRNA expression on the prognosis of OSCC patients.Cox regression model was used to analyze the prognostic factors of OSCC.Results The lncRNA CASC9 and YKT6 mRNA expression in OSCC cancer tissues were 3.12±0.57 and 2.69±0.42,respectively,which were significantly higher than those in adjacent tissues(1.02±0.25,1.13±0.21),and the differences were statistically significant(t=35.386,34.843,P＜0.05).The positive rate of YKT6 protein in OSCC cancer tissues was 81.82％(90/110),which was higher than that in adjacent tissues[9.09％(10/110)],and the difference was statistically signifi-cant(x2=117.333,P＜0.05).There was a positive correlation between lncRNA CASC9 mRNA expression and YKT6 mRNA expression in OSCC cancer tissues(r=0.788,P＜0.001).The lncRNA CASC9 and YKT6 mRNA expressions in cancer tissues of OSCC with TNM stages m to Ⅳ,low differentiation and lymph node metastasis were higher than those in cancer tissues of OSCC with TNM stages Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,the difference was statistically significant(all P＜0.05).The 5-year cu-mulative survival rate of lncRNA CASC9 high expression group and YKT6 mRNA high expression group was lower than that of lncRNA CASC9 low expression group and YKT6 mRNA low expression group,and the difference was statistically significant(Log-rank X2=7.080,8.741,P=0.008,0.003).High expression of ln-cRNA CASC9,high expression of YKT6 mRNA,TNM stage m to Ⅳ,low differentiation and lymph node me-tastasis were prognostic risk factors in OSCC patients.Conclusion The expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue is elevated,which can be used as tumor markers to evaluate the prognosis of OS-CC patients.

Objective To design a medical order pre-evaluation tool for perioperative prophylactic application of antibiotics,and to improve the efficiency of antibiotics management in hospitals during the perioperative period.Methods Using the open-source software R as the platform,a web application was built with tidy verse and shiny package based on related documents and guidelines.The discharge records of Affiliated Hospital of North Sichuan Medical College from April 1,2021,to December 31,2022,were retrospectively reviewed using the constructed pre-evaluation tool and compared with previous manual evaluation results using McNemar's Chi-squared test.Results This medical order pre-evaluation tool can quickly complete perioperative antibiotics order sampling,batch pre-evaluation,result statistics,visualization,and result output,and flexibly adjust the evaluation rules according to actual needs.The pre-evaluation tool is more efficient,with a review speed of 13.46 ms per medical record.Among the 2 642 discharge medical records of manual review,there was no significant difference between systematic pre-evaluation and manual evaluation results(ratio of prophylactic use:76.85%vs.78.21%)in terms of the type of use(preventive or curative)(P= 0.078).Among the 1 857 discharge records judged to be prophylactic for both manual and systematic reviews,the difference in unreasonable detection rate(39.90%vs.30.32%)was statistically significant(P＜0.001).Among the 63 typical ludicrous medical records confirmed by the review of clinical pharmacists with senior professional titles,60 were judged and limited by the pre-evaluation tool,and the detection rate of typical unreasonable was 95.24%.Conclusions The pre-evaluation tool based on R in this study can improve the efficiency of perioperative antibacterial drug evaluation.The evaluation conclusions and statistical results are reliable and are worthy of further development and application.

Abstract: Cancer immunotherapy, which is an attractive strategy harnessing the host's own immune system to remove tumor cells, has been widely used in clinical practice, yet with low response rate and immune-related adverse events. Unlike traditional chemotherapy, the targets of immunotherapy exhibit high spatial heterogeneity and are distributed in different cell types or secondary organelles, resulting in off-target and on-target toxicity, which greatly reduces the efficacy and safety of treatment. Due to the altered metabolic level, tumor tissues often display a lower pH than normal tissues. In addition, the endocytosis pathway is accompanied by continuous pumping of protons. Therefore, the variation of environmental pH values could serve as an ideal stimulus for precise drug delivery and release. In recent years, pH-responsive materials (e.g., polymers, biomacromolecules, lipid nanoparticles, biofilm, inorganic nanoparticles, and metal-organic frameworks) have been widely investigated in the field of cancer immunotherapy. This paper summarizes recent strategies of pH-responsive drug delivery systems based on different types of carriers, aiming to provide some reference for the design of next generation of tumor-targeting formulations in cancer immunotherapy.