Objective:To investigate the clinicopathological characteristics and influencing factors of kidney prognosis in primary IgA nephropathy (IgAN) patients.Methods:The data of primary IgAN patients diagnosed with renal biopsy in the First Affiliated Hospital of Anhui Medical University from January 2015 to September 2019 were retrospective analyzed. According to the level of baseline estimated glomerular filtration rate (eGFR) when performing renal biopsy, the patients were divided into group A[eGFR≥90 ml·min -1·(1.73 m 2) -1], group B[eGFR 61-89 ml·min -1·(1.73 m 2) -1] and group C[eGFR≤60 ml·min -1·(1.73 m 2) -1]. The clinical and pathological data were collected and compared among the three groups. Kaplan-Meier method was conducted for renal results, whereas the Cox proportional-hazards regression model was exploited to analyze the influencing factors of kidney prognosis in IgAN patients. Results:A total of 742 patients were included in the study, including 394 cases (53.1%) in group A, 203 cases (27.4%) in group B, and 145 cases (19.5%) in group C. There were 325 males (43.8%) and 417 females (56.2%). The median duration of renal biopsy was 6 (1, 24) months, and the median age was 36 years old (18-68 years old). As the baseline level of renal function decreased, the proportion of patients with nephrotic syndrome, hypertension, anemia and hyperuricemia and the levels of 24 h urinary protein, serum triglyceride and total cholesterol increased significantly (all P<0.05), while the proportion of gross hematuria episodes and the ratio of serum albumin to globulin significantly decreased (all P<0.05). For the aspect of pathological manifestations, the proportions of cell proliferation in capillaries (E1), segmental sclerosis or adhesion (S1), renal tubular atrophy or interstitial fibrosis (T1/2), globular sclerosis, renal arteriole wall thickening and vitreous degeneration, Lee's grade Ⅳ and Ⅴ increased with the decrease of baseline renal function (all P<0.05). Kaplan-Meier analysis showed that the cumulative renal survival rate decreased with the decline of baseline renal function (Log-rank χ2=88.510, P<0.001). As a result of multivariate Cox regression analysis, nephrotic syndrome ( HR=2.399, 95% CI 1.054-5.459, P=0.037), hypertension ( HR=1.806, 95% CI 1.071-3.048, P=0.027), low baseline eGFR (taking group A as the reference, group B: HR=2.383, 95% CI 1.053-5.392, P=0.037; group C: HR=6.878, 95% CI 3.074-15.393, P<0.001), IgG deposition ( HR=2.224, 95% CI 1.384-3.574, P=0.001) and globular sclerosis ( HR=2.075, 95% CI 1.230-3.501, P=0.006) were the independent influencing factors for renal progression in primary IgAN patients. Conclusions:The level of baseline renal function in primary IgAN patients can be used to predict the extent of clinic-pathological damage. Nephrotic syndrome, hypertension, low baseline eGFR, IgG deposition and globular sclerosis are the independent influencing factors for renal progression in primary IgAN patients.

Objective To evaluate prenatal diagnosis value of echocardiography in pathological types,differential diagnosis and accompanied malformations of fetal persistent truncus arteriosus(PTA).MethodsTwenty-four cases of PTA selected from 1 392 cases were analysed,who were definitely diagnosed to be suffered from cardiovascular malformation by fetal echocardiography.The ultrasound findings,pathological results and followed up were analysed.According to Van Praagh classification,the type IV PTA was excluded in this study which was classified into pulmonary artery atresia.Results The total PTA were 24 cases,in which 10 cases of A1 type,3 cases of A2 type,9 cases of A3 type,and 2 cases of A4 type.Nine cases of PTA accompanied other cardiac anomalies,and 1 case of PTA accompanied both cardiac anomalies and extracardial malformations.Two PTA cases were born,one was A1 type underwent surgical intervention,and the other was died due to multiple organ-failure.Fourteen PTA cases were termination and 7 cases were confirmed by pathology.Seven women pregnant again,of which 5 cases were born while only one was diagnosed atrial septal defect after birth,2 pregnant women were still during follow-up.Eight PTA cases follow-up were lost.Conclusions A1 type and A3 type of PTA have high incidence in fetus.Accompanied cardiac anomalies is certainly related to different types.Combination of multiple ultrosund techniques can diagnose PTA prenatally,make accurate classification and detect accompanying malformations,which is of great significance to offer proper pregnancy counselling and postpartum treatment.

Spinal muscular atrophy(SMA) is a serious neuromuscular degenerative disease that severely impairs the quality of life for patients and entire families.The emergence of disease-modifying treatments such as nusinersen and risdiplam has gradually changed the natural course of SMA patients.It is particularly important to include the activities of daily living(ADL) ability reported by patients or caregivers in the comprehensive assessment of SMA patients.There are many ADL-related assessment tools, and studies have found that disease-modifying treatments can somewhat improve the ADL ability of SMA children.This article reviews the progress on the effect of disease-modifying treatments on ADL in SMA patients, which can provide a reference for exploring more comprehensive and effective assessment tools and treatment decision-making in subsequent clinical practice.

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

Objective:To analyze the mutation pathogenicity of the novel compound heterozygous mutation in the PKHD1 gene causing autosomal recessive polycystic kidney disease (ARPKD) family, expand the PKHD1 gene mutation database, and explore the genotype-phenotype correlations of PKHD1 gene mutation causing ARPKD. Methods:Clinical data and peripheral blood of a patient with ARPKD caused by the novel compound heterozygous mutation in the PKHD1 gene and their family members were collected. High-throughput sequencing was used to detect pathogenic mutations in the proband, and PCR amplification and Sanger sequencing were used to verify the pathogenic mutations in the family. AlphaFold software was applied to predict changes in protein structure in the present or absent mutations, and the pathogenicity of mutations was analyzed. Results:The patient was a young male who underwent splenectomy due to liver cirrhosis and hypersplenism at age 7. He developed end-stage renal disease at age 22, requiring maintenance peritoneal dialysis, and died of severe pneumonia and septic shock at age 24. Genetic testing revealed three compound heterozygous mutations in the PKHD1 gene inherited from his parents: a missense mutation (c.5935G>A) inherited from the father and a missense mutation (c.1187G>A) and a novel splice mutation (c.6332+1_6332+2insG) from the mother. The single missense mutation allele likely contributed to the prolonged survival. c. 6332+1_ 6332+2insG is a novel splicing mutation that has not been reported in the past, which can lead to early termination of protein translation. This discovery expands the PKHD1 gene mutation database. c. 1187G>A (p.S396N) and c.5935G>A (p.G1979R) occur in the PA14 and G8 domains of the protein, respectively, and are associated with early and severe liver phenotypes in patients. Conclusions:The mutation types and amino acid localization of the PKHD1 gene are associated with the heterogeneity of clinical phenotypes in ARPKD patients. Analyzing structural changes in proteins before and after mutations can help understand the pathogenicity at a molecular level, establishing genotype-phenotype correlations and providing valuable insights for assessing prognosis and identifying high-risk ARPKD patients early.

Sodium and water retention are key and controllable risk factors that contribute to the increased risk of morbidity and mortality in patients with heart failure,and long-term continuous and effective volume management is an important strategy to help patients achieve an individualized state of optimal volume balance.The gradual application of digital health technology in the field of cardiovascular disease has provided new possibilities for volume management in patients with heart failure,while the relevant domestic studies and reports remain fewer.This article reviews the application of digital health technology in the assessment of volume status,management of volume status,volume hsk waming,health education and follow-up in patients with heart failure,and analyzes the existing problems and countermeasures,to provide a reference for digital volume management in out-of-hospital heart failure patients.

V-ATPases are a class of multi-subunit protein complexes that utilize energy derived from ATP hydrolysis for mediating H + transport across cell membranes, which plays an important role in a range of life activities by acidifying the intracellular and extracellular environment. Variants of V-ATPase genes may lead to complete or partial loss of V-ATPase activity, which in turn may impair the ability of type A intercalated cells in renal tubules to pump H + into the tubular lumen, ultimately resulting in the onset of autosomal recessive distal renal tubular acidosis (dRTA). With the rapid development of molecular techniques, ATP6V0A4 and ATP6V1B1 have now been identified as the pathogenic genes for dRTA. Moreover, animal and cell experiments have substantiated the implication of V-ATPase subunit genes including ATP6V1C2 and ATP6V1G3 in the development of dRTA, though clinical evidence is still limited. This article has reviewed recent progress on the genetic and molecular mechanisms of V-ATPase subunit gene variants which can lead to dRTA, which may shed light on the diagnosis and treatment of this disease.

Objective To explore the application value of simultaneous multi-slice(SMS)technique in diffusion tensor imaging(DTI)for evaluating brain glioma.Methods Thirty-four brain glioma patients were prospectively enrolled,and brain conventional DTI and SMS-DTI were acquired.The subjective scores of image quality,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were compared between SMS-DTI and conventional DTI,so were the numbers of whole brain fiber bundles,tumor relative fractional anisotropy(rFA)and relative mean diffusivity(rMD)obtained based on SMS-DTI and conventional DTI.Results Among 34 patients,there were 23 cases of high-grade glioma and 11 cases of low-grade glioma.No significant difference of subjective scores of image quality,tumor edge clarity nor magnetic susceptibility artifacts was found between SMS-DTI and conventional DTI(all P＞0.05).SNR and CNR on SMS-DTI were both lower than those on conventional DTI(both P＜0.05).No significant difference of the numbers of whole brain fiber bundles,rFA nor rMD of gliomas with different pathological grades was detected based on SMS-DTI compared with those on conventional DTI(all P＞0.05).Conclusion SMS applicated in DTI for evaluating brain gliomas was able to shorten acquisition time under the condition of ensuring image quality and quantitative analysis accuracy.

In order to develop clinical diagnostic tools for rapid detection of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.
Antigens, Viral ; immunology ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Genetic Vectors ; Genome, Viral ; Humans ; Nucleocapsid Proteins ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; isolation & purification ; metabolism ; SARS Virus ; genetics ; immunology ; Yeasts ; genetics

OBJECTIVE To analyze the effect of Huanglian Jiedu Decoction(HLJDD)on the intestinal flora and metabolites of Parkinson's disease(PD)model mice,and explore the mechanism of HLJDD in intervening in PD based on 16S rRNA technology and non-targeted metabolomics technology.METHODS The PD model of mice was induced by subcutaneous injection of MPTP 20 mg·kg-1·d-1 and peritoneal injection of probenecid 200 mg·kg-1·d-1,and the weight and behavior indexes of mice were measured after drug intervention.HPLC-QTRAP-MS/MS technique was used to detect the levels of neurotransmitters in the striatum of mice.The levels of striatal inflammatory factors were detected by ELISA.The changes of intestinal flora in mice were analyzed by 16S rRNA technology.UHPLC-Q-TOF-MS was used to detect endogenous metabolites in mouse striatum,Orthogonal partial least squares discriminant analysis(OPLS-DA)was adopted to screen potential differential metabolites,and MetaboAnalyst 5.0 was introduced to predict metabolic pathways associated with PD.RESULTS HLJDD significantly improved the motor symptoms and neuroinflammation of PD mice(P<0.01),regulated the level of neurotransmitters,and corrected the intestinal microbiota disorder of PD mice,manifes-ted by the increase of intestinal microbial diversity and the restoration of microbiota profile.After treatment with HLJDD,the abun-dance of Prevotella and Akkermansia in PD mice was significantly increased,and the abundance of Clostridium was decreased(P<0.01).The abnormal metabolite levels were restored mainly by regulating the tryptophan metabolic pathway in the feces and striatum of PD model mice.CONCLUSION HLJDD can significantly improve the pathological damage of PD model mice,and the regulation of disordered intestinal flora and tryptophan metabolism pathway may be the potential mechanism of HLJDD to intervene in PD.