Postprandial drowsiness is a clinical condition characterized by pronounced drowsiness after meals， while The Inner Canon of Yellow Emperor （《黄帝内经》） associates this condition with wei qi （defensive qi）. By analyzing the original texts of The Inner Canon of Yellow Emperor and perspectives from many medical professionals， it is found that the transition between wakefulness and sleep depends on the mutual induction of yin and yang， and that the two pathways of wei qi circulation intersect at the spleen and stomach. Based on this， the core pathogenesis of postprandial drowsiness is proposed to be either upper jiao obstruction or spleen-stomach dysfunction， leading to the stagnation of wei qi internally， then the mutual induction of yin and yang causes inward invasion of wei qi in the body， resulting in drowsiness； at this stage， the stagnated and inward invasive wei qi converges at the spleen and stomach， then merges into the circulation of zang-fu organs， rerouting through the Foot Taiyang Meridian， forming a circulation pattern described as "circulating from yin to yang". Treatment should focus on the root and branch simultaneously， with the primary goal of regulating the circulation of wei qi； facilitating its transition from yin to yang to restore the sleep-wake cycle. By proposing the model of wei qi circulating from yin to yang， this study offers novel insights on the understanding of postprandial drowsiness.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Objective To investigate the effect of AU-rich element RNA-binding factor 1(AUF1)on the proliferation,apoptosis,and migration abilities of hepatocellular carcinoma(HCC)cells and possible mechanisms,and to clarify the role and molecular mechanism of AUF1 in the progression of HCC.Methods The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients.CCK-8 assay,cell apoptosis assay,and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level,and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown.The t-test was used for comparison of continuous data between two groups;the Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival rates.Results There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue(P<0.05).The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC(P<0.05).Compared with the control group,the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells,while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells.The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β-catenin pathway and downregulated the protein expression level of β-catenin.Conclusion The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC,and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway.

Objective:To investigate the efficacy and safety of TC (paclitaxel and carboplatin) regimen combined with bevacizumab in the treatment of advanced ovarian cancer.Methods:A prospective randomized controlled study was conducted. A total of 102 patients with advanced ovarian cancer admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from January 2017 to April 2021 were selected and divided into the observation group and the control group according to random number table method, 51 cases in each group. The observation group was treated with TC regimen combined with bevacizumab, and the control group was treated with TC regimen. The clinical efficacy, carbohydrate antigen 125 (CA125) level, human epididymal protein 4 (HE4) level, thymidine kinase 1 (TK1) level, adverse reactions, the overall survival time, recurrence rate and mortality were compared between the 2 groups.Results:There were no statistically significant differences in baseline data such as age, tumor staging and tumor type between the observation group and the control group (all P > 0.05). The effective rate and the disease control rate of the observation group were 58.82% (30/51) and 88.24% (45/51), respectively, which were higher than those of the control group [37.25% (19/51) and 64.71 (33/51)], and the differences were statistically significant ( χ2 = 4.75, P = 0.029; χ2 = 7.85, P = 0.005). Before treatment, there were no statistically significant differences in CA125, HE4 and TK1 levels between the 2 groups (all P > 0.05). After treatment, CA125, HE4 and TK1 levels in the observation group were lower than those in the control group (all P < 0.05). There were no statistically significant differences in the incidence of myelosuppression, liver function damage, gastrointestinal reaction, proteinuria, diarrhea and abdominal pain, high blood pressure between the observation group and the control group (all P > 0.05). The 2-year overall survival rate of the observation group was higher than that of the control group (82.0% vs. 64.7%), while the recurrence rate of the observation group was lower than that of the control group [21.57% (11/51) vs. 45.10% (23/51)], and the differences were statistically significant (all P < 0.05). Conclusions:TC regimen combined with bevacizumab has favorable therapeutic effects and good safety in the treatment of advanced ovarian cancer, which is beneficial to prolong the survival time of patients.

Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.

Objective:To prepare anti-human IgE nanobody by phage display technology,and to establish a method for hyper-sensitivity detection of cat dander specific IgE antibody.Methods:Allergen bio-information of cat was searched in WHO/IUIS Allergen Database.After synthesizing sequence,recombinant cat dander allergenic protein Fel d 1 was expressed and purified in prokaryotic ex-pression system.Human IgE was used to immunize Bactrian camel and RNA were extracted from lymphocyte to construct phage dis-play library.Library capacity,diversity and insertion rate were analyzed,anti-human IgE nanobody were obtained by screening and identification.A magnetic particle chemical method for cat dander specific IgE antibody detection was established using recombinant allergen-coupled magnetic particles and acridine ester-labeled nanobodies.Results:Capacity of phage display library was 1.88×108 cfu/ml,insertion rate was 93.6%,and purity of nanobody was>95%.Linear range of the method based on nanobody was 0.1～100 U/ml,who was consistent with ImmunoCAP detection system by clinical data.Conclusion:Nanobody-based cat dander specific IgE antibody hypersensitivity assay is successfully prepared,providing a technical basis for auxiliary diagnosis of cat allergic diseases.

AIM:This study aimed to investigate the effects of sinomenine hydrochloride(SIN)on the ultra-structure of renal tissue and the expression of interferon gene-stimulating factor in db/db mice.METHODS:Sixteen 12-week-old male db/db mice were randomly divided into two groups:a model group and a sinomenine hydrochloride(SIN)group,each consisting of 8 mice.An additional 8 wild-type(WT)mice served as the normal control group.The sinome-nine hydrochloride group was administered the treatment for 8 weeks,followed by a 20-week observation period,while the normal and model groups received an equal volume of saline via gavage.Weekly measurements were taken for body weight and fasting blood glucose.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed,and 24-hour uri-nary microalbumin(ALB)levels,as well as serum inflammatory cytokines interleukin-1β(IL-1β),IL-6 and tumor necro-sis factor-α(TNF-α),were determined using ELISA.Pathological changes in renal tissue were evaluated through hema-toxylin-eosin(HE)staining,while ultrastructural alterations were examined using transmission electron microscopy.Im-munohistochemistry and Western blotting were employed to assess STING protein expression in renal tissue,and STING mRNA expression was quantified via RT-qPCR.RESULTS:Compared to the normal group,the model group exhibited significant increases in BUN,ALB,and SCr levels(P<0.01),alongside elevated inflammatory markers IL-1β,IL-6,and TNF-α(P<0.01).Notable pathological changes included leukocyte wall thickening in capillaries,inflammatory cell infiltration,increased mesangial matrix,disorganized and linear alignment of podocytes,and thickening of the basement membrane.Moreover,STING protein and mRNA expression levels were significantly elevated(P<0.01).In contrast,the sinomenine hydrochloride group demonstrated significantly reduced levels of renal function markers(BUN,ALB and SCr)compared to the model group(P<0.01),as well as decreased concentrations of inflammatory factors IL-1β,IL-6,and TNF-α(P<0.01).Improvements in renal histopathology included decreased leukocyte wall thickening,reduced inflam-matory cell presence,diminished mesangial matrix,and a significant reduction in foot process fusion,alongside thinner basement membranes.Both STING protein and mRNA expression levels were also significantly lower(P<0.01).CON-CLUSION:Sinomenine hydrochloride effectively mitigates renal tissue injury,improves ultrastructural alterations,and inhibits inflammatory responses in db/db mice.Its mechanism of action appears closely linked to the downregulation of STING protein and mRNA expression.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.