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 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.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

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.

ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022， and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022， among which the positive rate of measles IgM antibody was 33.55% （513/1 529）. The highest positive rate （20.73%） was from March to May ， and the positive rate of rubella IgM antibody was 6.80% （104/1 529）. The positive rate of both IgM was higher in males than that in females （P<0.05）. The IgM against measles was mainly detected in 0‒ years old （63.16%， 96/152） and 20‒ years old （45.61%， 161/353）. The IgM against rubella was mainly detected in 10‒20 years old （27.27%， 18/66）. The IgM antibody could be detected more easily from 4 to 28 days after eruption， and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years （2013‒2019）. There were 2 D8 genotype strains， and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles， and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children， in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization， and the surveillance of imported measles cases should be strengthened.

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

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.