1.Sini San Treats Liver Fibrosis by Regulating Polarization of Intrahepatic Kupffer Cells
Yanyu QU ; Qiao GENG ; Zhuxiu ZHOU ; Dongyang ZHENG ; Jianmin YAN ; Huan LIU ; Li CHEN ; Feng ZHANG ; Desong KONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):34-46
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.
2.The application prospects, ethical risks, and governance pathways of artificial womb technology
Chinese Medical Ethics 2025;38(5):656-662
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.
3.Advances and future research prospects in regulatory policies for clin-ical trials of artificial intelligence medical devices
Hao LIANG ; Shun WANG ; Cheng CUI ; Ling SONG ; Ailin SUN ; Man LI ; Jie QIAO ; Chun-li SONG ; Haiyan LI ; Yangguang ZHAO ; Haiyan LI ; Chenguang ZHANG ; Dongyang LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(3):427-431
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.
4.Epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan Province from 2012 to 2022
Lu LIU ; Yugang NIE ; Xiaoyu JI ; Guolong ZHANG ; Yang LIU ; Dongyang ZHAO ; Ning LI
Chinese Journal of Preventive Medicine 2025;59(8):1203-1208
Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.
5.Safety and efficacy of different anastomotic techniques following proximal gastrectomy: a meta-analysis
Dongyang SONG ; Zehua WANG ; Jie WANG ; Jinjie ZHANG ; Shasha LI ; Kun ZHANG ; Guohua GAO ; Wenqing HU
Chinese Journal of Gastrointestinal Surgery 2025;28(10):1179-1193
Objective:This meta-analysis compares the postoperative outcomes of the double-flap technique (DFT) versus esophagogastrostomy (EG), jejunal interposition (JI), double-tract reconstruction (DTR), and gastric tube anastomosis (GTA) following proximal gastrectomy for gastric cancer.Methods:Prospective and retrospective studies published from database inception until June 2025 were retrieved from PubMed, Embase, Web of Science, Scopus, CNKI, and Wanfang databases. Studies reporting at least one predefined outcome with extractable data were included. Outcomes of interest consisted of incidence of gastroesophageal reflux, overall postoperative complications, anastomotic leakage, anastomotic stenosis, and digestive reconstruction time. Two investigators independently performed literature screening, data extraction, and quality assessment. Randomized controlled trials (RCTs) were evaluated with the Cochrane ROB 2.0 tool, retrospective cohort studies with the Newcastle-Ottawa Scale (NOS), and single-arm studies with the JBI critical appraisal tool. Dichotomous outcomes were pooled using risk ratios (RRs), and continuous variables were summarized with standardized mean differences (SMDs), using fixed- or random-effects models based on I2 statistics. Publication bias was assessed via funnel plots and Egger's test.Results:A total of 55 studies published between 2007 and 2025 were included, comprising 5 RCTs and 50 retrospective studies. Among 4,380 patients, 732 underwent EG, 454 GTA, 1,480 DTR, 468 JI, and 1,246 DFT. Quality assessment indicated that all except six retrospective cohort studies (rated as moderate quality) were of high quality or had low risk of bias. Among the five reconstruction methods, DFT showed the lowest incidence of gastroesophageal reflux (6.6%, 82/1,246) and overall postoperative complications (11.6%, 144/1,246). JI had the lowest rate of anastomotic leakage (1.3%, 6/468), followed by DFT (1.4%, 18/1,246), and DTR had the lowest rate of anastomotic stenosis (2.4%, 36/1,480), followed by DFT (7.5%, 94/1,246). DFT required the longest operative time for reconstruction ([141.2 ± 597.6] minutes), and DTR required the shortest ([50.1 ± 39.0] minutes). Compared to EG, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR=0.13 ,95%CI: 0.03-0.55, P = 0.01), and no significant differences were observed in overall complications (RR=0.98, 95%CI: 0.55-1.74, P = 0.93), anastomotic leakage (RR = 0.81, 95%CI: 0.04-18.43, P = 0.90), or anastomotic stenosis (RR = 0.75, 95%CI: 0.09-6.39, P = 0.79). Compared to JI, DFT showed no significant differences in gastroesophageal reflux (RR = 0.36, 95%CI: 0.10-1.25, P=0.11), overall complications (RR=2.06, 95%CI: 0.30-14.11, P=0.46), anastomotic leakage (RR=2.05, 95%CI: 0.26-16.18, P=0.49), or anastomotic stenosis (RR=0.83, 95%CI: 0.10-7.17, P=0.87). Similarly, compared to DTR, DFT had a lower risk of overall complications (RR=0.70, 95%CI: 0.50-0.98, P=0.04) but a longer reconstruction time (SMD: 2.55, 95%CI: 0.31-4.79, P=0.03). No significant differences were found in gastroesophageal reflux (RR = 0.68, 95%CI: 0.35-1.30, P=0.24), anastomotic leakage (RR=0.59, 95%CI: 0.16-2.17, P=0.43), or anastomotic stenosis (RR=2.44 , 95%CI: 0.44-13.64, P=0.31). Compared to GTA, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR = 0.53, 95%CI: 0.33-0.88, P=0.01), but again there were no significant differences in overall complications (RR = 0.69, 95%CI: 0.41-1.16, P=0.16), anastomotic leakage (RR = 0.25, 95%CI: 0.03-2.14, P=0.21), or anastomotic stenosis (RR=0.65, 95%CI: 0.24-1.76, P=0.40). No significant publication bias was detected in the analysis (Egger's test P>0.05). Conclusions:Among the five common anastomotic methods after proximal gastrectomy, DFT demonstrates superior anti-reflux efficacy, outperforming EG and GTA in particular in preventing gastroesophageal reflux. DFT also exhibits a lower overall complication risk compared with DTR but maintains anastomotic safety comparable with that of the other techniques.
6.Epidemiological and molecular traceability analysis of the first cluster outbreak of D8 genotype measles in Henan Province
Xiaoxiao ZHANG ; Binghui DU ; Daxing FENG ; Wenhui WANG ; Jing LI ; Lili LIU ; Hui ZI ; Qihua WAN ; Songtao ZHAO ; Xiaoli WANG ; Xiaobo WU ; Yonghao GUO ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2025;59(8):1294-1298
In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.
7.Discovery of E0199: A novel compound targeting both peripheral NaV and KV7 channels to alleviate neuropathic pain.
Boxuan ZHANG ; Xiaoxing SHI ; Xingang LIU ; Yan LIU ; Xuedong LI ; Qi WANG ; Dongyang HUANG ; Weidong ZHAO ; Junru CUI ; Yawen CAO ; Xu CHAI ; Jiahao WANG ; Yang ZHANG ; Xiangyu WANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(1):101132-101132
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, NaV1.8, and NaV1.9 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 (IC50) for NaV1.9 by promoting sodium channel inactivation, and also effectively increased KV7.2/7.3, KV7.2, and KV7.5 channels, excluding KV7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated 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 therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.
8.Analysis of trace elements in whole blood in children aged 0-12 years in Henan province
Ke ZHAO ; Dongyang LI ; Xiaoli TIAN ; Dongmei YOU ; Yuling ZHAO ; Lixia DING
International Journal of Laboratory Medicine 2025;46(9):1114-1120
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.
9.Transcatheter arterial chemoembolization combined with argon-helium cryoablation for the treatment of hypervascular small hepatocellular carcinoma:analysis of its clinical efficacy
Dengwei ZONG ; Yanli MEMG ; Dongyang ZHANG ; Jincheng XIAO ; Jing LI
Journal of Interventional Radiology 2025;34(8):840-846
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.
10.Effect of toripalimab combined with chemoradiotherapy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma and immune function
Dongyang LIU ; Mengjiao CAI ; Li HE ; Ying LI
Journal of Clinical Medicine in Practice 2025;29(14):23-27,33
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.

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