Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Astragaloside Ⅳ （AS-Ⅳ） is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally， and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism， exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect， and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways， such as AMPK， NLRP3， NF-κB， JAK2/STAT3， and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Objective To observe the clinical efficacy of shugan yishen recipe in the treatment of postmenopausal estrogen receptor-positive breast cancer patients during endocrine therapy.Methods A total of 110 postmenopausal breast cancer patients undergoing aro-matase inhibitor endocrine therapy at Shanghai Municipal Hospital of Traditional Chinese Medicine from July 2021 to September 2023 were divided into observation group and control group by random number table method,with 55 patients in each group..Both groups received standard treatment;the observation group also took shugan yishen recipe,while the control group also took shugan yishen recipe placebo,treatment for 12 weeks.The clinical efficacy,traditional Chinese medicine syndrome scores,bone metabolism,tumor markers,T-cell subsets(CD4+,CD8+,CD4+/CD8+)of the two groups were observed,and the safety was evaluated.Results A total of 106 patients completed the experiment,with 53 patients in each group.After treatment,the total clinical effective rate was 75.5％in the observation group,and 58.5％in the control group,the clinical effect of the observation group was better than that of the control group(P＜0.01).Compared with before treatment,TCM syndrome scores in both groups were decreased(P＜0.01).After treatment,β-c-terminal te-lopeptide of type-Ⅰ collagen(β-CTX),carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and CD8+were all decreased compared with those before treatment(P＜0.05);N-mid osteocalcin(N-MID),CD4+,CD4+/CD8+were higher than those before treatment(P＜0.01).After treatment,β-CTX,N-MID,CA153,CD8+and CD4+/CD8+in the observation group were significantly better than those in the control group(P＜0.01).Conclusion Shugan yishen recipe can improve bone metabolism abnor-malities caused by endocrine treatment in postmenopausal patients with estrogen receptor-positive breast cancer,reduce serum tumor marker levels,enhance immune function of patients,and is safe and effective.

Objective To explore the clinical efficacy and safety of modified PPH combined with partial internal anal sphincterotomy in the treatment of circular mixed hemorrhoids.Methods Patients with annular mixed hemorrhoids were divided into two groups by a completely randomized controlled method.54 patients in the experimental group were treated with modified PPH combined with partial internal anal sphincterotomy,while 51 patients in the control group were treated with conventional PPH.The postoperative indicators,perioperative and long-term complication rates of the two groups were compared,and the clinical efficacy and safety were observed.Results The operation time in the experimental group was(48.35±4.37)minutes,which was higher than that in the control group(36.42 ±6.21)minutes(P＜0.05).The incidence of postoperative anastomotic stenosis in the experimental group was 1.9％,lower than 15.6％ in the control group(P＜0.05).Anal pain,urinary retention,first defecation time,long-term anal distention,the experimental group was significantly better than the control group,the difference was statistically significant(P＜0.05);The hospitalization time in the experimental group(4.8±0.62)days was not significantly different from that in the control group(5.1±0.54)days(P＞0.05).The amount of intraoperative bleeding and anastomotic bleeding in the experimental group[(17.28±2.22)ml,3.7％]were not significantly different from those in the control group[(16.75± 2.13)ml,3.9％](P＞0.05).Conclusion Compared with conventional PPH,the modified PPH combined with partial internal anal sphincterotomy slightly increases the operation time,but does not increase the risk of anastomotic bleeding,the incidence of rectal fistula,the amount of surgical bleeding,and the length of hospital stay.It can significantly improve postoperative anal pain,urinary retention,long-term distention symptoms,shorten the time of first defecation,ease the difficulty of defecation,and significantly reduce postoperative anastomotic stenosis,The long-term efficacy and safety are good.

Objective After hydrogen bonding between collagen ( COL) and silk fibroin ( SF ) at different concentrations, a composite scaffold with adjustable stiffness was prepared by combining with gel system, and its physical and chemical properties were characterized. Methods SF with different qualities was dissolved in sodium alginate (SA) solution, then COL solution at different concentration and calcium carbonate ( CaCO3 ) powder were added. The hydrogels of SC1, SC2, and SC3 groups were obtained by taking out the mixed solution and adding some gluconic acid lactone ( GDL) powder, and different SF scaffolds were obtained after freeze drying. Results The SF scaffolds with adjustable stiffness were successfully prepared. The compression moduli of SC1, SC2, and SC3 groups were (17. 31±2. 73), (24. 12±1. 81), (32. 54±1. 81) kPa, respectively. The innerstructure of the scaffolds was observed. From SC1 group to SC3 group, pores of the scaffolds were smaller and fewer, and hydrophilicity of the materials become better and better. Conclusions Three-dimensional ( 3D) porous scaffolds with different matrix stiffness can be prepared by changing the concentration of SF and COL solution. The concentration of SF and COL is proportional to the compression modulus, water absorption, water retention and swelling rate of SF scaffolds, while inversely proportional to porosity. The findings of this study are expected to provide theoretical guidance for construction of scaffolds with appropriate matrix stiffness for inducing osteogenic differentiation of mesenchymal stem cells

ObjectiveTo explore the protective effect of modified Shengmaisan on cardiac function in elderly patients with myocardial infarction based on the nuclear factor-κB/induction nitric oxide synthase/nitric oxide （NF-κB/iNOS/NO） signaling pathway. MethodA total of 136 elderly patients with myocardial infarction treated in Qinghai Hospital of Traditional Chinese Medicine from december 2019 to december 2021 were included. They were randomly divided into an observation group and a control group， with 68 cases in each group. The control group was treated with conventional western medicine， and the observation group was treated with conventional western medicine + modified Shengmaisan. Both groups were treated with percutaneous coronary intervention for revascularization. The indexes related to cardiac function and levels of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and matrix metalloproteinase-9 （MMP-9） were analyzed and compared between the two groups. The echocardiographic index， cardiac function classification， changes in the NF-κB/iNOS/NO signaling pathway， oxidative stress indexes， and major adverse cardiovascular events （MACE） of the two groups were compared. ResultCompared with those before treatment， the levels of N-terminal B-type natriuretic peptide （NT-pro BNP）， serum inflammatory indexes， left ventricular end systolic volume （LVESV）， left ventricular end diastolic volume （LVEDV）， NO， iNOS， NF-κB p65， and methane dicarboxylic aldehyde （MDA） were significantly reduced （P<0.05，P<0.01）， and the left ventricular ejection fraction （LVEF） and superoxide dismutase (SOD） were significantly increased （P<0.05）. After treatment， as compared with the control group， the levels of NT-pro BNP， serum inflammatory indexes， LVESV， LVEDV， NO， iNOS， NF-κB p65， and MDA in the observation group were significantly reduced （P<0.05）， and those of LVEF and SOD were significantly increased （P<0.05）. There was no significant difference in the New York Heart Association (NYHA) cardiac function classification between two groups. The incidence of MACE in the observation group was significantly lower than that in the control group （P<0.05）. ConclusionModified Shengmaisan can significantly reduce NT-pro BNP and levels of serum inflammatory indexes in elderly patients with myocardial infarction， improve echocardiographic indexes， regulate the NF-κB/iNOS/NO signaling pathway， and reduce the oxidative stress index and the incidence of MACE， which has a good protective effect on cardiac function.

Diabetic cardiomyopathy （DCM） is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes， distinct from other cardiovascular diseases such as coronary heart disease， valvular heart disease， or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance， activation of various inflammatory responses， increased oxidative stress， impaired coronary microcirculation， and accumulation of advanced glycation end products （AGEs）. Among various inflammatory responses， the activation of the NOD-like receptor protein 3 （NLRP3） inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation， subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently， extensive experimental studies on traditional Chinese medicine （TCM） have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts， such as Astragalus polysaccharide and ginsenoside Rb₁， single drugs like Coriolus and Cordyceps， and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang， as well as acupuncture and TCM exercise therapy， can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation， reduce inflammatory responses， inhibit myocardial remodeling in DCM， and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM， as well as the research progress on TCM in exerting anti-inflammatory effects in this field， aiming to provide new insights for the development of therapeutic approaches for DCM.