The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line

Objective:To investigate the value of serum free light chain(sFLC)and serum calcium ion in the diagnosis and prognosis of multiple myeloma(MM).Methods:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group,and 40 healthy volunteers were selected as the control group.The differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc between the two groups were compared.Meanwhile,the differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc in different international staging systems(ISS),chemotherapy efficacy and prognosis patients were analyzed.Results:The levels of sFLC-κ[(98.39±21.19)vs(12.01±4.45)mg/L],sFLC-λ[(210.20±45.54)vs(14.10±5.11)mg/L]and proportions of hypocalcemia(65％vs 0)in the observation group were significantly higher than those in the control group(P＜0.05),while sFLC-κ/λ ratio[(0.44±0.10)vs(0.87±0.12)]and serum calcium ions[(1.98±0.46)vs(2.42±0.40)mmol/L]were significantly lower than those in the control group(P＜0.05).The sFLC-κ,sFLC-λ,the proportion of hypocalcemia and the course of hypocalcemia in ISS stage Ⅲ patients in the observation group were significantly higher than those in stage Ⅰ and Ⅱ patients(P＜0.05),while sFLC-κ/λ ratio,and serum calcium ions were significantly lower than those in stage Ⅰ and Ⅱ patients(P＜0.05).The levels of sFLC-κ[(107.76±21.22)vs(94.67 ±20.11)mg/L],sFLC-λ[(245.54±41.12)vs(205.54±50.22)mg/L]of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia[(0.42±0.04)vs(0.47±0.06);P＜0.05].The levels of sFLC-κ[(107.29±20.14)vs(91.11±18.92)mg/L],sFLC-λ[(247.98±42.26)vs(179.29±39.32)mg/L]in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy[(0.43± 0.10)vs(0.50±0.09);P＜0.05)].The area under the ROC curve for sFLC-κ,sFLC-λ,sFLC-κ/λ predicting ineffective chemotherapy was 0.803,0.793 and 0.699 respectively,P＜0.05.There was no significant difference in sFLC-κ,sFLC-λ,sFLC-κ/λ ratio,serum calcium ion,hypocalcemia ratio and hypocalcemia course between survival and death patients(P＞0.05).Conclusion:sFLC and serum calcium are related to 1SS stage of MM patients.sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients.However,the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

Objectives:Present study aimed to use quantitative flow ratio based on Murray's law to analyze the risk factors of impaired side branches perfusion without naked eye visible slowing of blood flow in branches after interventional treatment of true bifurcation lesions of the coronary arteries. Methods:A total of 211 patients with non-left main coronary artery true bifurcation coronary artery disease who underwent percutaneous coronary intervention(PCI)in Hunan Provincial People's Hospital from June 2022 to September 2023 were continuously enrolled,with a total of 234 bifurcation lesions.The general clinical indicators,anatomical characteristics of coronary artery bifurcation lesions,branch protection methods,postoperative branch TIMI blood flow and other data were collected,and quantitative flow ratio(μQFR)was measured for postoperative branch blood vessels.Post-PCI μQFR<0.8 was considered as impaired branch perfusion and was included in the postoperative impaired branch perfusion group(n=51,53 branch lesions).Patients with μQFR≥0.8 were included in the postoperative normal branch perfusion group(n=160,181 branch lesions).Multivariate Logistic regression analysis was used to evaluate the effects of various clinical and anatomical factors on branch perfusion after PCI. Results:The post-PCI branch flow grading of all patients was TIMI grade Ⅲ.The postoperative branch μQFR of 53 vessels(22.6％)in the group with impaired postoperative branch perfusion was 0.70±0.10,and 0.93±0.05 in the group with normal postoperative branch perfusion,and the difference between the two groups was statistically significant(P<0.001).Compared with the postoperative group with normal branch perfusion,the postoperative group with impaired branch perfusion was featured with an elevated branch lesion length,branch reference diameter,postoperative branch opening diameter stenosis rate,postoperative branch narrowest lumen diameter stenosis rate,and a lower main branch-to-branch diameter ratio,preoperative branch narrowest lumen diameter stenosis rate,and preoperative main branch μQFR,all of which were statistically significant(all P<0.05).The postoperative branch opening diameter stenosis rate(r=-0.490,P<0.001),postoperative branch narrowest lumen diameter stenosis rate(r=-0.788,P<0.001),preoperative branch narrowest lumen diameter stenosis rate(r=-0.280,P<0.001),branch narrowest lumen diameter(r=-0.469,P<0.001),branch lesion length(r=-0.157,P=0.016)were negatively correlated with postoperative branch μQFR,and branch reference diameter(r=0.173,P=0.008),main branch/side branch diameter ratio(r=0.194,P=0.003),and branch opening diameter(r=0.328,P<0.001)were positively correlated with postoperative branch μQFR,and none of them were significantly correlated with clinical baseline data(all P>0.05).Multifactorial logistic regression analysis showed that following four factors were independent risk factors for impaired branch perfusion:postoperative stenosis of the narrowest branch lumen diameter(OR=1.228,95％CI:1.144-1.318,P<0.001),postoperative stenosis of the branch opening diameter(OR=1.110,95％CI:1.055-1.168,P<0.001),postoperative stenosis of the narrowest lumen diameter of the main branch(OR=1.115,95％CI:1.042-1.192,P=0.001),and length of the branch lesion(OR=1.121,95％CI:1.021-1.231,P=0016). Conclusions:Some of the patients whose branch flow reached TIMI grade Ⅲ after PCI are still faced the risk of hemodynamical impairment and should be functionally evaluated after PCI.The postoperative stenosis rate of the narrowest branch lumen diameter,postoperative stenosis rate of the branch opening diameter,postoperative stenosis rate of the narrowest lumen diameter of the main branch,and branch lesion length are the risk factors of branch perfusion impairment after PCI for coronary bifurcation lesions.

Objectives:to analyze the efficacy of percutaneous coronary intervention(PCI)for complex left main(LM)lesions combined with chronic total occlusion(CTO)of the right coronary artery. Methods:Ninety patients with complex left main lesions hospitalized in Hunan Provincial People's Hospital from January 2019 to December 2022 were consecutively included.According to the coronary angiographic vascular lesions,patients were divided into complex left main lesions combined with right coronary artery CTO(observation group,n=30)and complex left main lesions without right coronary artery CTO(control group,n=60).The baseline clinical data,intraoperative conditions,angiographic results,and postoperative follow-up results of the patients were analyzed and compared between the two groups. Results:Fifty-eight(64.4%)out of the 90 patients were male.There was no statistically significant difference between the two groups in terms of baseline clinical data(all P>0.05),left main lesion condition(P=1.000),left main calcification condition(P=0.249),and preoperative TIMI flow grading(P=1.000).In the comparison between observation group and the control group,intraoperative occurrence of no-reflow(3.3%vs.5.0%,P=1.000),hypotension(10.0%vs.8.3%,P=1.000),pericardial effusion(3.3%vs.0%,P=0.333),the percentage of intravascular ultrasound(IVUS)use(86.7%vs.90.0%,P=0.635),and the use of circulatory assist device(P=0.699),and the proportion of intraoperative coronary spinning(26.7%vs.21.7%,P=0.597)were all similar between the two groups.The median follow-up time was 14.50(11.83,15.85)months,and the differences in the incidence of major adverse cardiovascular events(MACE)such as recurrent angina,acute myocardial infarction,rebleeding,readmission for heart failure,and cardiac death(31.0%vs.32.1%,P=1.000)were not statistically significant between the observation group and the control group. Conclusions:PCI revascularization may be a viable approach for elderly patients with complex LM lesions with multiple underlying disease,and combined right coronary artery CTO,intolerance and reluctance to CABG.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To investigate the efficacy and influencing factors of initial 131I therapy in serum thyroglobulin (Tg) antibody (TgAb)-positive patients with papillary thyroid cancer (PTC). Methods:A retrospective analysis was performed on the clinical data of 1 624 patients with PTC who underwent 131I therapy in Henan Provincial People′s Hospital between January 2017 and January 2023. The patients were divided into TgAb-positive group (246 cases (36 males, 210 females), age: 43.5(31.0, 52.0) years) and TgAb-negative group (1 378 cases (439 males, 939 females), age: 44.0(34.0, 53.0) years). The efficacy was evaluated 6-12 months post 131I therapy based on serological tests (TgAb, Tg) and imaging results (ultrasonography, CT, 131I-whole body scan (WBS), SPECT/CT imaging), and the patients were divided into disease persistence/recurrence and non-persistence/recurrence groups. The χ2 test was used to analyze the difference in efficacy between the TgAb-positive group and the TgAb-negative group. Among TgAb-positive patients, the clinical characteristics of disease persistence/recurrence group were compared with those of non-persistence/recurrence ones by χ2 test or Mann-Whitney U test, and the independent risk factors affecting the efficacy of 131I therapy were analyzed by binary logistic regression. Results:The disease persistence/recurrence were found in 38 cases (15.4%, 38/246) of the TgAb-positive group and 143 cases (10.4%, 143/1 378) of the TgAb-negative group, with a statistically significant difference between the two groups ( χ2=5.42, P=0.020). Among the TgAb-positive patients, statistically significant differences were found in lymph node metastasis (35 vs 23 cases), the interval between surgery and 131I therapy (2.0(1.5, 3.0) vs 2.3(2.0, 3.0) months), stimulated Tg(sTg) level before the initial 131I therapy (0.18(0.04, 5.78) vs 0.04(0.04, 0.46) μg/L), and TgAb level before the initial 131I therapy (40.15(19.13, 156.15) vs 22.25(7.53, 76.20) kU/L) between disease persistence/recurrence group and non-persistence/recurrence group ( χ2=117.13, z values: -2.29, -2.41, -2.80, all P<0.05). Lymph node metastasis was an independent risk factor (odds ratio( OR)=89.326, 95% CI: 25.005-319.106, P<0.001) for the efficacy of 131I therapy in patients with TgAb-positive PTC. Conclusion:The overall efficacy of 131I therapy in patients with TgAb-positive PTC is relatively poor, and lymph node metastasis is an independent risk factor for the efficacy of 131I therapy, while the level of TgAb is not an independent risk factor for the efficacy of 131I therapy in these patients.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*