ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5（TGR5）/NOD-like receptor protein 3（NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1） pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank， model， ursodeoxycholic acid， and Yinchenhao Tang groups. Except the blank group， other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid （0.1 g·kg^-1） and Yinchenhao Tang （9.23 g·kg^-1） were administered by gavage. The blank group and the model group were administrated with the same amount of pure water， once a day for 3 days. The blood and liver tissue samples were collected， and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin （IL）-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β， IL-18， TGR5， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5， NLRP3， ASC， Caspase-1， and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group， the model group showed elevated levels of alanine amino-transferase （ALT）， aspartate transferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， and total bilirubin （TBil） in the serum （P<0.01）， inflammatory cell infiltration， hepatocyte swelling， and bile duct epithelial cell proliferation in the liver， raised levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA and protein levels of TGR5 （P<0.01）， up-regulated mRNA levels of IL-18 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， and NLRP3 （P<0.05）， and up-regulated protein levels of NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， and GSDMD （P<0.05）. Compared with the model group， the ursodeoxycholic acid group showed declined levels of AST （P<0.01）， TBA （P<0.01）， TBil （P<0.01）， and ALT （P<0.05） in the serum， lowered levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of NLRP3 （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， IL-18 （P<0.05）， and ASC （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.05）， and down-regulated protein levels of NLRP3， ASC， Caspase-1， and GSDMD （P<0.05）. Compared with the model group， the Yinchenhao Tang group showed lowered levels of ALT， AST， ALP， TBA， and TBil in the serum （P<0.01）， declined levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of IL-1β （P<0.01）， NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， and IL-18 （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.01）， and down-regulated protein levels of Caspase-1 and GSDMD （P<0.05）. The liver tissue of the administration groups showed reduced infiltration of inflammatory cells， reduced swelling of hepatocytes， and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.

ObjectiveThis study aims to investigate the mechanism of Yinchenhao Tang （YCHT） in regulating macrophage polarization to alleviate cholestatic liver injury，focusing on the TLR4/NF-κB signaling pathway as the entry point. MethodsCholestasis was induced in Wistar rats through a single gavage of 100 mg·kg^-1 α-naphthyl isothiocyanate （ANIT） dissolved in olive oil. The animals were randomly divided into four groups：Model group，YCHT group，ursodeoxycholic acid （UDCA） group （n=10），and a blank group （n=10） that received only 5 mL·kg^-1 olive oil. The YCHT group received 9.23 g·kg^-1·day^-1 of YCHT by gavage，and the UDCA group was treated with 0.1 g·kg^-1·day^-1 of UDCA suspension. Both the normal and model groups were given an equal volume of normal saline，all for three consecutive days. Serum liver function was assessed using an automatic biochemical analyzer. Hematoxylin-eosin （HE） staining was used to observe liver tissue morphology. Levels of tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），transforming growth factor-β （TGF-β），and interleukin-10 （IL-10） were quantified in liver homogenate supernatants via enzyme-linked immunosorbent assay （ELISA）. Western blot analysis measured the relative protein expression of Toll-like receptor 4 （TLR4），nuclear factor-κB （NF-κB），CD206，inducible nitric oxide synthase （iNOS）， CD86，and arginase-1 （Arg-1）. The relative mRNA expression of TLR4/NF-κB，CD206，iNOS，CD86，and Arg-1 in liver tissue was evaluated using real-time quantitative PCR. ResultsCompared with the normal group，the model group exhibited significantly elevated levels of alkaline phosphatase （ALP），total bile acid （TBA），total bilirubin （TBil），aspartate aminotransferase （AST），and alanine aminotransferase （ALT） （P<0.01）. There was a portal area expansion and pronounced inflammatory cell infiltration. The expression of pro-inflammatory markers TNF-α and IL-1β was significantly upregulated （P<0.01），and macrophage markers CD86 and CD206 showed positive expression. Protein and mRNA expressions of iNOS and CD86 were significantly elevated （P<0.01）. The mRNA and protein expressions of the related pathway molecules TLR4 and NF-κB were significantly increased （P<0.01）. Compared with those in the model group， the liver function indicators in the YCHT group showed significant decreases （P<0.05， P<0.01）. The bile duct hyperplasia was significantly alleviated， and the tissue structure became more orderly. The levels of IL-1β and TNF-α were significantly reduced （P<0.01）， while the expression levels of IL-10 and TGF-β significantly increased （P<0.05， P<0.01）. The expression of CD86 significantly decreased （P<0.01）， and the expression of CD206 significantly increased （P<0.01）. The protein and mRNA expressions of iNOS and CD86 significantly decreased （P<0.01）， and those of Arg-1 significantly increased （P<0.01）. The protein and mRNA expressions of CD206 significantly increased （P<0.05， P<0.01）， and the mRNA and protein expressions of related pathway molecules TLR4 and NF-κB significantly decreased （P<0.01）. ConclusionYCHT ameliorates cholestatic liver injury in rats by improving bile metabolism，reducing bile duct dilatation，and mitigating inflammation. These effects are achieved through the inhibition of M1 macrophage activation and the promotion of M2 macrophage polarization，likely via modulation of the TLR4/NF-κB signaling pathway.

Cholestatic liver injury refers to the bile production， secretion， and excretion disorder caused by various reasons. It induces liver injury， metabolic disorders， and dysfunction of the hepatobiliary system， which can further develop into liver fibrosis， cirrhosis， liver failure， and even death. At present， the preferred drug for clinical treatment is ursodeoxycholic acid， which， however， induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat， eliminating dampness， and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory， anti-oxidation， bile acid balance-regulating， hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion， reducing inflammatory response， inhibiting oxidative stress， alleviating endoplasmic reticulum stress， inhibiting hepatocyte apoptosis， and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research， aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.

Wu Jutong's academic thoughts are inherited from Ye Tianshi and traced back to Zhongjing,and have a unique under-standing and play of the evil invading Shaoyang.Wu Jutong believes that Shaoyang has two major functional characteristics:ascending and pivoting.The principle of treating evil invading Shaoyang is to follow the ascending nature of Shaoyang and restore the pivoting function of Shaoyang.For Shaoyang fire-heat syndrome,follow Shaoyang to ascend and disperse to penetrate heat,and often use light,scavenging and dispersing products;for Shaoyang phlegm-fluid syndrome,creat Xiangfu Xuanfuhua Decoction to benefit the liver and gallbladder and resolve phlegm-fluid;for malaria invading Shaoyang,turn the pivot to stop malaria,and use Xiaochaihu Decoction and Qinghao Biejia Decoction for the treatment;for yin evil invading Shaoyang and Jueyin,Xiao Chaihu Decoction and Bupleurum chinense DC.are often used to turn the pivot of Shaoyang and warm and unchoke Jueyin.The contraindications of Xiao Chaihu Decoction are al-so summarized.

Objective To study the characteristics of animal models of pulmonary fibrosis so as to provide a reference for the standardization of such models,and to guide research on the pathogenesis,diagnosis,and treatment of pulmonary fibrosis.Methods Studies using experimental pulmonary fibrosis in animals published in the past 10 years were retrieved from the CNKI,Wanfang,VIP,SinoMed,and PubMed databases.Factors including animal species,sex,modeling method,and detection index were summarized,and the data were analyzed using Excel.Results A total of 292 eligible studies were included.The animals mainly included SD rats,Wistar rats,and C57BL/6 mice,and most were male.The most common modeling drugs were bleomycin,paraquat,and silica suspension,mainly administered by intratracheal injection,with a typical modeling cycle of 28 d.The detection indexes mainly comprised lung tissue pathology and measurements of protein expression,cytokine levels,and biochemical indexes.Conclusions SD rats and C57BL/6 mice were the most commonly used animals for experimental pulmonary fibrosis,and intratracheal injection of bleomycin(5 mg/kg)was the most frequently used modeling method.This approach allows for the straightforward and effective replication of pathological features resembling human pulmonary fibrosis,and may serve as a reference for future experimental studies using animal models of pulmonary fibrosis.

Objective To study the action of Sijunzi decoction preventing disuse atrophy and its mechanism on the pathway of muscle stem cell(MuSC)/myonuclear domain(MND)based on the theory of sedentary behavior damaging muscle.Methods 40 male rats were randomly divided into the normal group,tail hanging group(model group),tail hanging+exercise group(exercise group),tail hanging+distilled water group(DW group),tail hanging+sijunzi decoction(Chinese medicine(CM)group);grip strength of limbs was measured by Grip Strength Meter for rats and mice;the wet weight of quadriceps femoris(QF)was measured by electronic scales;concentrations of actin and myosin were detected by ELISA;the cross section area(CSA)and myonuclear numbers were detected with Image Pro 6.0,and then MNDs were calculated;the expressions of pair box gene 7(Pax7)and myogenic differentiation antigen(MyoD)were detected by immunofluorescence.Results Compared with those in the normal group,grip strength,QF wet weight,the myosin concentration,the CSA and MND in the model and DW groups were all decreased,the numbers of Pax7 were increased significantly;compared with those in the model and distilled water groups,grip strength,QF wet weight,the myosin level,CSA and myonuclear numbers in the exercise group and CM groups were increased,and the numbers of Pax7 and MyoD positive cells were increased,markedly,however the number of Pax7 positive cells in the exercise group was more than that in the CM group significantly.Conclusion Sijunzi decoction can prevent disuse atrophy and its possible mechanism is related to the activation the MuSC/MND pathway.

Objective:To explore the potential influencing factors of parenteral nutrition-associated cholestasis（PNAC）in extremely premature infants.Methods:A total of 83 cases of extremely premature infants who received parenteral nutrition and developed PNAC admitted to Shanxi Children's Hospital between October 2020 and October 2023 were selected as the case group，while 99 extremely premature infants who received parenteral nutrition but did not develop PNAC during the same period were selected as the control group. Basic information such as gender，gestational age，birth weight，and duration of parenteral nutrition were collected for the extremely premature infants. The health status of the infants at 1 minute and 5 minutes after birth was assessed using the Apgar standardized scoring method. One week after parenteral nutrition,platelet count(PLC)，mean platelet volume(MPV)，and platelet volume distribution width(PDW) were measured. Univariate analysis and non-conditional Logistic regression were used to analyze the potential influencing factors of PNAC in extremely premature infants after parenteral nutrition. Receiver operating characteristic(ROC) curves were plotted to evaluate the performance of the influencing factors and combined predictive factors in predicting PNAC in extremely premature infants receiving parenteral nutrition.Results:The 1-min and 5-min Apgar scores in the case group were lower than those in the control group( P<0.001);the percentages of gestational hypertension in mothers and postnatal infections in children were higher than those in the control group( P<0.05);and the duration of parenteral nutrition was longer than that in the control group( t=4.655, P<0.001), the differences were statistically significant. In the case group, after one week of parenteral nutrition,PLC was lower than that in the control group( t=4.949, P<0.001),MPV was higher than that in the control group( t=12.193, P<0.001), and PDW was higher than that in the control group( t=10.744, P<0.001), the differences were statistically significant.Multifactorial Logistic analysis showed that after adjusting for gender and gestational age，1-minute Apgar score（ OR=0.898），5-minute Apgar score（ OR=0.900），postnatal infection（ OR=1.256），duration of parenteral nutrition（ OR=1.426），one week after parenteral nutrition，PLC（ OR=0.902），MPV（ OR=1.441），and PDW（ OR=1.195）were independent influencing factors for PNAC in extremely premature infants（all P<0.05）. ROC curves showed that each factor and combined predictive factors had certain efficacy in predicting the occurrence of PNAC in extremely premature infants after parenteral nutrition. Conclusion:One-minute Apgar score,5-minute Apgar score，duration of parenteral nutrition，postnatal infection，one week after parenteral nutrition，the PLC,MPV and PDW are independent influencing factors for PNAC in extremely premature infants receiving parenteral nutrition.Each factor predicts the efficacy of parenteral nutrition for PNAC in extremely premature infants, and relevant factors should be controlled in time to reduce the incidence of PNAC in extremely premature infants.

Objective:To investigate the application of blended team-based learning (BTBL) in improving the clinical reasoning ability of general practitioners from different sources.Methods:From September to December in 2021, 52 postgraduates of general practice in Tongji University School of Medicine were selected as subjects, and according to their study background and practice experience, they were divided into residency training group, community group, and specialist group. BTBL was adopted for all students in the course of clinical reasoning in general practice, and a 4-station objective structured clinical examination (OSCE) test was conducted before and after the course to evaluate teaching effectiveness from the aspects of medical history collection, physical examination, doctor-patient communication, and medical record writing. SPSS 22.0 was used to perform a statistical analysis of data. Continuous data were expressed as mean±standard deviation, and an analysis of variance or the Kruskal-Wallis test was used for comparison between groups; the paired samples t-test or the Wilcoxon signed rank sum test was used for comparison of normally distributed or non-normally distributed data within each group. Categorical data were expressed as frequency and percentage. Results:There was a significant change in the score of physical examination after the course in the community group (44.88±9.17 vs. 78.06±12.11, t=-12.49, P<0.001), the specialist group (45.85±8.18 vs. 68.65±13.10, t=-6.43, P<0.001), and the residency training group (42.38±15.30 vs. 76.44±16.46, t=-5.98, P<0.001). There was a significant change in the score of doctor-patient communication after the course in the community group (63.00±13.84 vs. 78.69±7.10, t/Z=-4.33, P<0.05) and the residency training group (60.00±15.50 vs. 70.88±6.44, t/Z=-2.12, P<0.05). There was also a significant change in the score of medical record writing after the course in the community group (60.19±17.96 vs. 79.69±14.25, t=-2.96, P<0.05), the specialist group (47.77±12.59 vs. 80.31±12.93, t=-6.26, P<0.05), and the residency training group (37.00±15.50 vs. 75.88±15.88, t=-7.25, P<0.05). The score of medical record writing before the course was 60.19±17.96 in the community group, 47.77±12.59 in the specialist group, and 37.00±15.50 in the residency training group, with a significant difference between the three groups ( χ2=13.04, P=0.001); after the course, the score of medical record writing was 78.69±7.10 in the community group, 63.46±19.40 in the specialist group, and 70.88±6.44 in the residency training group, with a significant difference between the three groups ( χ2=10.13, P=0.006). Conclusions:In the course of clinical reasoning in general practice, BTBL can improve teaching efficiency, save teaching resources, and play the role of promoting strengths and avoiding weaknesses.

Objective:To investigate the predictive value of the cancer antigen 125 (CA 125) elimination rate constant K (KELIM) score for no visible residual disease (R0) and prognosis in high-grade serous ovarian carcinoma (HGSOC) patients undergoing neoadjuvant chemotherapy (NACT)+interval debulking surgery (IDS). Methods:A retrospective analysis was conducted on 78 HGSOC patients treated with NACT+IDS at Beijing Hospital, from June 2014 to June 2024. The KELIM score was calculated, and its predictive value for R0 resection, chemotherapy response score (CRS), platinum-free interval (PFI), progression-free survival (PFS) time, and overall survival (OS) time was analyzed.Results:(1) The mean age at diagnosis was (61.9±9.9) years. The mean KELIM score was 1.1±0.4, with 44 patients having KELIM score≥1 and 34 having KELIM score <1. (2) Patients with KELIM score ≥1 had significantly higher rates of R0 resection (84% vs 56%; P=0.006), CRS3 grading (41% vs 0; P<0.001), and PFI ≥6 months (84% vs 53%; P=0.04) compared to those with KELIM score <1. Additionally, the median PFS time (18.7 vs 13.2 months; P<0.001) and OS time (34.8 vs 29.9 months; P=0.007) were significantly longer in the KELIM score ≥1 group. Chemosensitivity: patients with PFI <6 months had a significantly lower median KELIM score than those with PFI ≥6 months (0.8 vs 1.2; P=0.005). Surgical outcome: patients achieving R0 resection had a significantly higher median KELIM score than those without R0 (1.2 vs 0.7; P<0.001). (3) Univariate analysis identified non-R0 resection, CRS3 grading, lack of poly adenosine diphosphate ribose polymerase (PARP) inhibitor maintenance therapy, and KELIM score <1 as significant risk factors for OS time (all P<0.05). Multivariate analysis confirmed non-R0 resection ( HR=3.78,95% CI: 1.13-12.66; P=0.031), no PARP inhibitor maintenance ( HR=7.41,95% CI:1.82-30.15; P=0.005), and KELIM score <1 ( HR=5.14,95% CI:1.41-18.72; P=0.013) as independent risk factors for OS time. Conclusions:The KELIM score may serve as a predictive marker for chemosensitivity, R0 resection, PFS time, and OS time in HGSOC patients undergoing NACT+IDS. KELIM score<1 is an independent risk factor for OS.

Objective To screen out the predictive factors for prognosis of migraine patients with patent foramen ovale(PFO)after occlusion,and to observe the value of predictive model based on these factors.Methods A total of 102 migraine patients with PFO who underwent occlusion of PFO were retrospectively included.Based on right to left shunt(RLS)grade in contrast-enhanced transcranial Doppler(TCD)and changes of migraine disability assessment(MIDAS)grade after occlusion,the patients were divided into effective group(n=56)and ineffective group(n=46).Patients'basic data and imaging data including contrast-enhanced TCD and transesophageal echocardiography(TEE)before occlusion were compared between groups.Independent predictive factors were screened using multivariate logistic regression,then a predictive model was established,and its performance was evaluated.Results Compared with ineffective group,effective group had a lower proportion of female patients,a higher proportion of patients with aura symptoms,also higher MIDAS scores before occlusion,lower left to right shunt(LRS)velocities through the defect,and higher RLS grades in contrast-enhanced TCD and TEE right heart contrast echocardiography before occlusion(all P＜0.05).Patients'gender,LRS velocity through the defect and RLS grade in TEE right heart contrast echocardiography before occlusion were all predictive factors for prognosis of migraine patients with PFO after occlusion of PFO(all P＜0.05).The established model demonstrated good discrimination,calibration and clinical net benefit.Conclusion Patients'gender,LRS velocity through the defect and RLS grade in TEE right heart contrast echocardiography before occlusion were all significant predictors of prognosis of migraine patients with PFO after occlusion,and the predictive model established based on these factors demonstrated certain clinical value.