This paper summarizes Professor LIU Shangyi's clinical experience in treating acute mastitis based on the "membrane collaterals" theory. It is considered that constraint and stagnation of the membrane collaterrals is the primary pathogenic factor， with damp， heat， phlegm， and stasis being the secondary manifestations. If untreated， the condition can progress to heat toxin injuring the membrane. In treatment， the emphasis is diffusing and unblocking membrane collaterals， unblocking breast and relieving constraint. The clinical course of the disease can be divided into three stages including the early stage with mild constraint heat， the middle stage with escalating toxic heat， and the later stage with a decline of pathogens but deficiency of healthy qi. In correspondence， self-made Tongru Formula （通乳方） for diffusing membrane and venting constraint， self-made Toumo Jiedu Formula （透膜解毒方） for unblocking membrane and relieving toxin， and Tuoli Xiaodu Powder （托里消毒散） with modifications for restoring membrane and rectifying healthy qi should be used， respectively.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective To analyze the monitoring data of cardio-cerebrovascular diseases prevention and control system in Yichang in 2022, and to provide data support and experience for the precise prevention and treatment of cardio-cerebrovascular diseases. Methods Acute cardiovascular and cerebrovascular event data were collected from the Yichang Cardio-cerebrovascular Events Monitoring System from January 1, 2022 to December 31, 2022. Descriptive analysis was conducted for the data collected. Statistical analysis was performed using SPSS 20.0 software, and a chi-square test was used to analyze the count data. Results A total of 37,217 cases of cardio-cerebrovascular events were monitored in Yichang in 2022. The crude incidence and the standardized incidence were 983.84/100,000 and 541.55/100,000, respectively. The incidence in males was higher than females (554.93/100,000 vs 428.91/100,000，χ² =464.52，P＜0.05). The top three diseases were cerebral infarction, acute myocardial infarction, and cerebral hemorrhage. The incidence of events increased with age, and 79.80% of the cases were over 60 years old. The main onset time was from May to August. Conclusion The use of the cardio-cerebrovascular events monitoring system in Yichang and the implementation of ^“mandatory reporting card^” monitoring can timely obtain the epidemic characteristics of the diseases, provide support for the precise formulation of prevention and control strategies and measures, reduce underreporting rates, and improve the monitoring system, which is worthy of reference and promotion.

Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P＜0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.

Objective:To explore the impact of sleep disturbances on the symptoms and functional impairment outcomes in children with attention deficit hyperactivity disorder (ADHD) and their path analysis.Methods:A cross-sectional study was made.Two hundred and seventy-eight ADHD children aged 6-12 years were selected from the Center for Cognition and Sleep, the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2022 to March 2023.The Swanson, Nolan and Pelham Rating Scale Ⅳ was used to evaluate the core symptoms of ADHD (namely, attention deficit and hyperactivity).The sleep disturbance scale for children was used to assess sleep disturbances [including disorders in initiating and maintaining sleep(DIMS), sleep breathing disorders, sleep-wake transition disorders (SWTD), disorders of arousal, disorders of excessive somnolence (DOES) and nocturnal hyperhidrosis].The Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) was used to assess functional impairment (in family, learning and school, life skills, self-concept, social activities, and risky activities).The descriptive statistical analysis, t test, multivariate linear regression and path analysis were used for statistical analysis. Results:Compared with those without sleep disturbances, ADHD children with sleep disturbances had significantly more serious functional impairment in family [(0.87±0.42) scores vs.(0.63±0.45) scores, P<0.001], learning and school [(0.75±0.37) scores vs.(0.62±0.35) scores, P=0.011], life skills [(1.30±0.37) scores vs.(1.08±0.30) scores, P<0.001], self-concept [(1.20±0.57) scores vs.(0.92±0.49) scores, P<0.001], social activities [(0.88±0.44) scores vs.(0.67±0.42) scores, P<0.001] and risky activities [(0.28±0.24) scores vs.(0.21±0.21) scores, P=0.043].The results of multivariate linear regression analysis showed that after adjusting for gender, age, total intelligence quotient, and core symptoms of ADHD, the regression coefficients of DOES in domains of family ( B=0.02, P=0.042) and life skills ( B=0.03, P<0.001) and the regression coefficient of DIMS in self-concept were still statistically significant ( B=0.02, P=0.013).The path analysis results showed that DOES ( β=0.170, P=0.004), attention deficit ( β=0.223, P<0.001) and hyperactivity ( β=0.385, P<0.001) directly affected WFIRS-P.DOES indirectly affected WFIRS-P through attention deficit ( β=0.270, P<0.001), and SWTD indirectly affected WFIRS-P through hyperactivity ( β=0.199, P=0.004). Conclusions:Severer sleep disturbances are associated with severer functional impairment in children with ADHD, and sleep phenotypes can directly or indirectly affect functional impairment outcomes in different domains in children with ADHD through core symptoms of ADHD.

Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

OBJECTIVE: To investigate the molecular mechanism of weak D phenotype in a Chinese family. METHODS: Routine Rh typing tests were performed first, and RHD exons 1-10 of the proband and his family members were sequenced by first-generation sequencing. RHD zygosity was also determined. Third-generation sequencing was used to analyze the haplotypes of the RHD gene. RESULTS: The proband showed a weak D serological phenotype. First-generation sequencing revealed a c.787G>A point mutation in exon 5. The family pedigree investigation showed that the proband and his younger sister had the same serological phenotype and molecular mechanism. His father carried this gene mutation, while his mother and younger brother were normal. Hybrid box was not detected, suggesting that all the family members did not have a haplotype with a complete deletion of the RHD gene. The results of third-generation sequencing showed that the proband and his sister inherited the weak D allele from their father and the non-functional allele RHD -CE(3-9)-D from their mother, respectively. CONCLUSION Third-generation sequencing technology enables haplotype analysis of the RHD gene and can detect complex genotypes such as genetic exchanges between RHD and RHCE combined with other mutations.
Female ; Humans ; Male ; Alleles ; Exons ; Genotype ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Pedigree ; Phenotype ; Rh-Hr Blood-Group System/genetics* ; East Asian People/genetics*