ObjectiveTo investigate the mechanism by which Sini San （SNS） treats liver fibrosis through regulating the polarization of intrahepatic Kupffer cells. MethodsSixty SPF-grade male Balb/c mice were randomized into blank control， model， silymarin （0.2 g·kg^-1）， and low-， medium-， and high-dose （2.93， 5.85， 11.70 g·kg^-1， respectively） SNS groups. A mouse model of liver fibrosis was induced by intraperitoneal injection of CCl₄. After 5 weeks of administration， the body mass， liver pathological changes ［Hematoxylin and Eosin （HE）， Masson， and Sirius red staining］， serum biochemical indicators ［alkaline phosphatase （ALP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）］， liver fibrosis markers ［procollagen type Ⅲ （PCⅢ）， laminin （LN）， and hyaluronic acid （HA）］， inflammatory cytokines ［interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10）］， and fibrosis-related proteins ［α-smooth muscle actin （α-SMA）， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ）］ were assessed. A co-culture system of THP-1 cells （M1 macrophages） and human hepatic stellate cells （LX-2） was established. The cell experiment was designed with blank control （LX-2 alone）， model （LX-2 + M1 macrophages）， and low-， medium-， and high-dose SNS （co-culture with 5%， 10%， or 20% SNS-containing serum， respectively） groups. Cell viability， inflammatory cytokines， and macrophage phenotype were examined. Human primary hepatic Kupffer cells were allocated into blank control， M1 （LPS 100 μg·L^-1+IFN-γ 20 μg·L^-1）， M2 （IL-4 20 μg·L^-1+IL-13 20 μg·L^-1）， M1+M2， M1+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M1 conditions for 24 h）， M2+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M2 conditions for 24 h）， and M1+M2+SNS groups （supplemented with 10% SNS-containing serum for 2 h after culture under M1+M2 conditions for 24 h）， and the expression of nuclear factor-κB （NF-κB） p65 and signal transducer and activator of transcription 3 （STAT3） at protein and mRNA levels was determined. ResultsCompared with the blank group， the model group exhibited increased serum levels of ALT， AST， ALP， PCⅢ， LN， HA， IL-6， and TNF-α， upregulated protein and mRNA levels of α-SMA， Col Ⅰ， and Col Ⅲ in the liver tissue （P<0.05， P<0.01）， and decreased IL-10 level and STAT3 mRNA level （P<0.05， P<0.01）， accompanied by marked collagen deposition and inflammatory infiltration in the liver. Compared with the model group， all doses of Sini San reversed these alterations （P<0.05， P<0.01）， with the high-dose group showing the most pronounced effects. Cell experiments demonstrated that， compared with the blank control group， the model group had elevated levels of pro-inflammatory cytokines （IL-1β， IL-6， and TNF-α） and upregulated protein and mRNA levels of M1 markers ［cluster of differentiation 86 （CD86， inducible nitric oxide synthase （iNOS）， and monocyte chemoattractant protein-1 （MCP-1）］ （P<0.01）， along with declined level of IL-10 and downregulated expression of M2 markers ［（CD163， CD206， and arginase-1 （Arg-1）］ （P<0.05，P<0.01）. Compared with the model group， treatment with Sini San-containing serum at various concentrations lowered the levels of pro-inflammatory cytokines and expression of M1 markers （P<0.05， P<0.01）， while increasing the IL-10 level and M2 marker expression （P<0.05， P<0.01）. Additionally， Sini San downregulated the mRNA level of NF-κB and upregulated the mRNA level of STAT （P<0.05， P<0.01）. In the experiment with human primary Kupffer cells， compared with the blank group， the M1 group showed increased NF-κB p65 expression （P<0.01） and decreased STAT3 expression （P<0.05）， whereas the M2 group exhibited increased STAT3 expression （P<0.01）. Compared with the respective model groups， Sini San-containing serum reversed the M1-induced overexpression of NF-κB p65 （P<0.05， P<0.01） and further enhanced the M2-induced STAT3 expression （P<0.05， P<0.01）. ConclusionSini San can inhibit the NF-κB p65/STAT3 signaling pathway and repolarize intrahepatic Kupffer cells from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype to attenuate inflammation and suppress hepatic stellate cell activation and collagen deposition， thereby exerting anti-fibrotic effect.

Objective: To analyze the trend in disease burden of nasopharyngeal carcinoma-related among middle-aged and elderly population in China from 1994 to 2023, so as to provide evidence for formulating targeted screening and intervention strategies. Methods: Data on prevalent cases, standardized prevalence, incident cases, standardized incidence, death cases, standardized mortality, disability-adjusted life years (DALY) and standardized DALY rate of nasopharyngeal carcinoma among the population aged ≥45?years in China were collected through the Global Burden of Disease (GBD) 2023 database. The average annual percent change (AAPC) was used to evaluate the trend in disease burden. A four-factor decomposition method was used to estimate the contributions of population size, age structure, prevalence variation and disease severity to the alterations in death cases and DALY caused by nasopharyngeal carcinoma. Results: The standardized prevalence of nasopharyngeal carcinoma among Chinese middle-aged and elderly population rose from 46.54/105 in 1994 to 59.81/105 in 2023, presenting an upward trend (AAPC=0.760%, 95%CI: 0.561%-0.973%). The standardized incidence, standardized mortality and standardized DALY rate decreased from 13.66/105, 10.90/105 and 318.79/105 to 10.75/105, 3.87/105 and 111.20/105, respectively, with declining trends (AAPC=-0.757%, 95%CI: -0.882% to -0.620%; AAPC=-3.554%, 95%CI: -3.681% to -3.419%; AAPC=-3.444%, 95%CI: -3.564% to -3.307%). In 2023, the standardized prevalence, incidence, mortality and DALY rate among males reached 86.96/105, 15.84/105, 5.88/105 and 172.49/105, which were higher than 33.45/105, 5.82/105, 1.92/105 and 51.66/105 in females. Decomposition analysis indicated that expanded population scale, population ageing and prevalence change exerted favourable effects on the reduction of death cases and DALY caused by nasopharyngeal carcinoma, whereas disease severity produced an offsetting adverse effect. Conclusions The overall disease burden of nasopharyngeal carcinoma among middle-aged and elderly population in China declined from 1994 to 2023, yet males suffered from a comparatively heavy burden. The beneficial impacts from population expansion, population ageing and prevalence change on burden reduction were partially counteracted by disease severity.

The research on artificial womb technology and “fetus and newborn” by Deby et al.， as well as the Food and Drug Administration’s discussion on whether the world’s first human clinical trial of “artificial womb” technology should be approved， have sparked a new wave of research on artificial womb technology. By extending and deepening relevant foreign research， the three potential application prospects of artificial womb technology were clarified， including rescuing extremely preterm infants， reducing the burden of pregnancy， and assisting advanced maternal age. The ethical risks it faced were pointed out， encompassing the moral status of the gestational entity was questionable， and the risks of technological experimentation could not be quantified. The governance pathways were clarified， involving multi-layered ethical considerations to complete the clear identification of the gestational entity’s identity， and multi-faceted patient-doctor consultations to achieve clear risk notification. Through discussions on the application prospects， ethical risks， and governance pathways of artificial womb technology can improve human welfare and realize the technology for human use.

Objective To investigate the the levels of magnesium,lead,iron,zinc,copper,manganese,calci-um in whole blood in children aged 0-12 years in Henan province,understand the health status of children and provide a basis for their nutrition and health management.Methods Data were collected from totally 135 385 children aged 0-12 years who underwent trace element testing at Zhengzhou Kingmed Clinical Labo-ratory Inc.from 2019 to 2023 were selected,and agilent inductively coupled plasma mass spectrometer was used to detect seven elements(magnesium,lead,iron,zinc,copper,manganese,and calcium).The elemental detection method in the laboratory has been strictly methodologically verified,and has participated in the ex-ternal quality assessment organized by National Center for Clinical Laboratories.Grouping was conducted based on gender,age,season,region,and year to compare the deficiencies and lead exceedances of six elements(magnesium,iron,zinc,copper,manganese,calcium)under different conditions.Results In this study,the mean P-values of seven elements in different age groups,gender groups,year groups,and regional groups were all＜0.001.Except for lead with a P-value of 0.002,all other elements in different season groups were＜0.001.The P-values were all less than 0.05,indicating statistically significant differences.Among them,Mag-nesium,iron,and zinc in children's whole blood showed an increasing trend with age,while copper,manga-nese,and calcium showed a decreasing trend with age.The proportions of children aged 0-1 years with iron,zinc,and manganese deficiencies were the highest,at 24.70％,48.20％,and 0.65％,respectively.The highest proportion of copper and calcium deficiency was in the age range of 11-12 years old,accounting for 20.43％and 0.17％respectively.The highest proportion of lead exceeding the standard was 0.87％among children aged 0-1.Except for manganese and calcium levels,the levels of the other five elements were higher in boys than in girls.Magnesium and copper levels were highest in spring,iron,zinc,and calcium levels were highest in winter,and manganese and lead levels were highest in summer.Magnesium deficiency,calcium deficiency,and lead excess were showing a decreasing trend year by year.Among them,the lead levels of children in Sanme-nxia and Jiyuan were relatively high compared to other areas.Conclusion 0-2 years children are mainly char-acterized by calcium and zinc deficiency in Henan province.Attention should be paid to iron and zinc supple-mentation in infants and young children.At the same time,it should also be noted that the deficiency rate of copper increases with age,and attention should be paid to the supplementation of copper in children.

Objective To evaluate the efficacy of transcatheter arterial chemoembolization(TACE)combined with argon-helium cryoablation(AHC)in the treatment of hypervascular small hepatocellular carcinoma(sHCC).Methods The clinical data of 35 patients with hypervascular sHCC,who received TACE combined with AHC at the Affiliated Cancer Hospital of Zhengzhou University of China from March 2018 to February 2019,were retrospectively analyzed.All patients were treated with TACE treatment first,after 3-7 days the patients received AHC therapy.The postoperative 1-,3-,and 6-month curative effect were evaluated,and the postoperative 1-,3-,and 5-year survival rates were calculated.The liver function and immune function indicators,as well as the serum tumor markers were detected.The adverse reactions during treatment were recorded.Results The postoperative 1-,3-,and 6-month objective remission rate(ORR)were 100.00％,94.29％and 91.43％respectively,and the disease control rate(DCR)were 100.00％,100.00％and 97.14％ respectively.The overall survival(OS)was(46.54±2.88)months,and the postoperative 1-,3-,and 5-year survival rates were 94.29％(33/35),65.71％(23/35)and 48.57％(17/35)respectively.The postoperative 3-day serum levels of ALT,AST and TBIL were significantly elevated when compared with their preoperative baseline levels(all P＜0.05),which returned to preoperative levels in 2 weeks after treatment(P＞0.05).The postoperative 2-week CD4+％and CD4+％/CD8+％ratio were remarkably increased when compared with their preoperative values(both P＜0.05),while the postoperative 2-week AFP,AFP-L3％,DCP and GPC3 levels were strikingly decreased when compared with their preoperative values(all P＜0.001).None of the patients developed procedure-related severe complications after treatment.Conclusion For the treatment of hypervascular sHCC,TACE combined with AHC has satisfactory clinical efficacy and safety.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective:To investigate the clinical outcomes of arthroscopic suture anchor fixation for acute bony Bankart lesions.Methods:Data of 49 patients with acute bone Bankart injury treated with suture anchor fixation under arthroscopy at the Affiliate Nanjing Drum Tower Hospital of Nanjing University School of Medicine from February 2019 to July 2024 were retrospectively analyzed, including 34 males and 15 females, aged 46.4±17.7 years (range, 18-81 years). Body mass index was 26.3±4.2 kg/m 2 (range, 19.8-37.9 kg/m 2). There were 17 patients with left shoulder and 32 patients with right shoulder. The time from injury to operation was 12.6±10.5 d (range, 1-50 d). CT three-dimensional reconstruction showed that the area of bone defect accounted for 20.1%±11.4% (range, 8%-49%) of the glenoid area. According to the degree of bone defect, there were 38 cases in the bone defect area ≤25% group and 11 cases in the bone defect area >25% group. All 49 patients received shoulder arthroscopic fixation with wire anchor. All 49 the patients were treated under shoulder arthroscopy using suture anchor technique. Using American Shoulder & Elbow Surgeon (ASES) score, University of California, Los Angeles (UCLA) score, Rowe score as well as shoulder range of motion to evaluate shoulder function. The position and healing of the fracture mass were evaluated with shoulder joint CT and three-dimensional reconstruction at immediate and final follow-up. Results:The incision healed in one stage and no infection occurred in all patients. All 49 patients were followed up for a period of 3 to 81 months, with an average follow-up of 23.8±20.2 months. At the final follow-up, the mean forward elevation, external rotation, and internal rotation improved from 126.1°±20.3°, 36.9°±14.0°, and 10±2 preoperatively to 167.1°±15.5°, 66.8°±8.3°, and 6±1 at the last follow-up, respectively ( P<0.05). At the final follow-up, the mean ASES score, UCLA score, and Rowe score were all significantly improved from 41.3±11.9, 14.2±6.1 and 46.9±14.7 preoperatively to 89.7±7.8, 31.5±3.6 and 92.4±7.4, respectively ( P<0.05). The differences between the final follow-up and preoperative values for forward elevation in the bone defect area >25% group and the bone defect area ≤25% group were 43°±20° and 41°±21°, respectively. The differences in lateral external rotation were 34°±8° and 29°±18°, while the differences in internal rotation (measured by hand-behind-back reach) were 5±2 and 4±2, respectively. None of these differences were statistically significant. The differences between the final follow-up and preoperative scores in the bone defect area >25% fracture fragment group and the bone defect area ≤25% group were as follows: ASES score, 50.9±14.4 vs. 47.7±12.8; UCLA score, 18.4±3.2 vs. 17.0±6.9; and Rowe score, 40.5±13.5 vs. 46.9±15.0. None of these differences were statistically significant. CT examination at the last follow-up showed that all fractures were healed, all patients in the bone defect area ≤25% group achieved good reduction, and 3 patients in the bone defect area >25% group had step-offs on the glenoid surface. Postoperative shoulder adhesion occurred in 5 patients, which was improved after intensive abduction and external rotation exercise. Conclusions:Arthroscopic suture anchor fixation is effective for the bone defect area ≤25% bony Bankart lesions, offering advantages of minimal invasiveness and rapid recovery. For lesions involving more than the bone defect area 25% of the glenoid surface, enhanced fixation strength is recommended to prevent fracture fragment displacement.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.