Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

ObjectiveDisruption of epithelial layer may instantaneously induce the generation of endogenous electric fields, which was proved to play an important role in guiding the cell migration and promoting wound healing. PIEZO1 is a kind of mechanic sensitive channel, may be regulated by voltage, is proved to involve in chemotactic migration of cells and play an important role in the process of wound healing. In this paper, the role of PIEZO1 and its downstream proteins FAK and integrin β1 in the electric field guided cell migration were investigated by HaCaT cells (human immortalized keratinocyte). MethodsCell migration was tracked by Living Cell Imaging System in directed current (DC) electric field (EF). Inhibitors and RNAi techniques were applied to study the function of PIEZO1 and other related proteins in electric fields. Western blot was used to detect the expression and phosphorylation levels of integrin β1 and FAK in electric field guided migration under EF stimulation. ResultsPiezo1 RNAi as well as Ruthenium red and GsMTx4 treatment all significantly inhibited the electrotaxis of HaCaT cells. Electric field stimulation with GsMTx4 treatment alone increased FAK phosphorylation level and the expression of integrin β1. Electric field promoted the expression level of integrin β1 and the phosphorylation level of FAK. Inhibiting the expression of PIEZO1 by RNAi significantly attenuated the phosphorylation level of FAK under EF stimulation. Inhibition of integrin β1 and FAK by inhibitor significantly decrease the electric field guided cell migration. ConclusionPIEZO1 as well as integrin β1 and FAK are involved in the electric field guided cell migration of HaCaT cells. Electric field signals regulate the expression of integrin β1 and the activation of FAK through PIEZO1-mediated signal pathway to orchestrate cell migration.

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

ObjectiveTo simulate the microstructure and mechanical properties of tendon tissue and promote its regeneration and repair, electrospinning technology was used to prepare L-polylactic acid (PLLA) fiber membranes loaded with different nano zinc oxide contents and with oriented structures. Physical and chemical characterization and biological performance evaluation were carried out to explore their effects on tendon cell proliferation and differentiation. MethodsPreparation of PLLA fiber scaffolds and PLLA/ZnO fiber scaffolds containing different mass fractions of nano ZnO was performed using electrospinning technology. The physicochemical properties of the scaffold were characterized by scanning electron microscopy, mechanical stretching, and EDS spectroscopy. The scaffold was co-cultured with mouse tendon cells to detect its biocompatibility and regulatory effects on cell differentiation behavior. ResultsThe fiber scaffolds were arranged in an oriented manner, and zinc elements were uniformly distributed in the fibers. The tensile strength and Young’s modulus of PLLA/0.1%ZnO fiber scaffolds were significantly higher than PLLA fiber scaffolds. The number of cells on the surface of PLLA/0.1%ZnO fiber scaffold was significantly higher than that of the PLLA group, and the activity was better; mouse tendon cells exhibit directional adhesion and growth along the fiber arrangement direction. ConclusionThe oriented PLLA/0.1%ZnO fiber scaffold had excellent physicochemical properties, which can significantly promote the oriented growth, proliferation and differentiation of tendon cells. It is expected to be used for tendon tissue regeneration and repair in the future.

AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P＜0.05);increased,degree of renal fibrosis,and renal fibrosis area(P＜0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and decreased expressions of IGF-1R mRNA and protein(P＜0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P＜0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P＜0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and increased expressions of IGF-1R mRNA and protein(P＜0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P＜0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Objective:To explore the disease spectrum and corresponding clinical indicators of infantile cholestasis so as to provide a basis for the diagnosis of this type of disease at an early stage.Methods:The clinical data was collected from 203 hospitalized children diagnosed with infantile cholestasis at the Department of Gastroenterology of Maternal and Child Health Care, Guiyang City, from January 2018 to March 2023, including 130 males and 73 females. Patients general condition, personal history, and blood biochemical test indicators, including liver and coagulation function, blood ammonia, blood lipid profile, blood sugar, TORCH, thyroid function, and others, were retrospectively analyzed after admission. Cholangiography and high-throughput gene sequencing were performed in certain patients. The etiology of the enrolled cases were analyzed. Children's clinical data were compared with distinct inherited metabolic liver diseases (Group A) and biliary atresia (Group B). The statistical analysis was conducted using the t-test, Mann-Whitney test, Kruskal-Wallis test, or χ2 test, according to different data. Results:In 33 cases, infectious factors—primarily CMV infection—were the etiology of cholestasis. Forty cases had aberrant bile duct development, primarily biliary atresia, choledochal cysts, and intrahepatic bile duct dysplasia. In 26 cases, genetic metabolic factors mainly included citrin protein deficiency, sodium-taurocholate co-transporting polypeptide deficiency, and Alagille syndrome. 11 cases had drug/poisoning factors (parenteral nutrition-associated cholestasis). 19 cases had idiopathic infantile cholestasis. Three cases had other factors; however, all of them had Kawasaki disease. 71 cases had an unclear diagnosis. There was no statistically significant difference in terms of gender and age between groups A and B ( P>0.05). The alkaline phosphatase (ALP) and bile acid levels were significantly higher in Group A than Group B, with a P<0.05, while the gamma glutamyltransferase (GGT), direct bilirubin (DBil), and albumin levels were lower than those in Group B, with a P<0.05. The cytomegalovirus infection rate was higher in Group B (62.50%) than Group A (34.62%), and the difference between the two groups was statistically significant ( χ2=3.89, P<0.05). The alanine aminotransferase, aspartate aminotransferase, GGT, DBil, and albumin were significantly lower in patients with citrin protein deficiency than those in patients with biliary atresia, while ALP, bile acid, and blood ammonia were higher than those in patients with biliary atresia. Patients with sodium-taurocholate co-transporting polypeptide deficiency had higher bile acid than patients with biliary atresia, while the DBil was lower than that in patients with biliary atresia, and the difference was statistically significant ( P<0.05). Conclusion:Infantile cholestasis etiology is diverse. ALP, bile acids, GGT, DBil, and albumin levels can serve as simple indicators for early-stage differentiation between inherited metabolic liver disease and biliary atresia. The cholestasis etiology should be determined as early as possible following biliary atresia exclusion by actively completing genetic metabolic gene detection.