AIM To investigate the ameliorative effects of Schisandrol A(Sol A)in Suhuang antitussive capsule on post-infectious cough(PIC).METHODS The in vivo mouse PIC model was established by intratracheal instillation of lipopolysaccharide(LPS)combined with cigarette smoke exposure.The mice were randomly divided into the control group,the model group,the Suhuang antitussive capsule group(14 g/kg),the montelukast sodium positive control group(3 mg/kg),and low and high dose Sol A groups(10,30 mg/kg).The in vitro PIC model was established by stimulating human bronchial epithelial cells(BEAS-2B)with LPS.The cells were divided into the control group,the model group,the Suhuang antitussive capsule group(10 μg/mL)and low and high dose Sol A groups(3,10 μmol/L).HE and Masson staining were used to detect the pathological changes of the lung and bronchial tissues.ELISA was used to detect the levels of IL-1β,IL-6,TNF-α,ROS,MDA,SOD and GSH in the lung tissues.RT-qPCR was used to detect the IL-1β,IL-6 and TNF-α mRNA expressions in BEAS-2B cells.And Western blot was applied to detect the protein expressions of p-PI3K,p-Akt,NOX4,SIRT1,p-ERK,Fibronectin,E-cadherin,Vimentin and α-SMA in mouse lung tissue and BEAS-2B cells.RESULTS Compared with the model group,the groups intervened with Sol A or Suhuang antitussive capsule displayed prolonged cough latency(P＜0.01);reduced cough frequency(P＜0.01);relieved pulmonary inflammatory cell infiltration and collagen deposition in PIC mice;decreased pulmonary levels of IL-1β,IL-6,TNF-α,ROS,MDA and protein expressions of Fibronectin,Vimentin,α-SMA,p-ERK,p-PI3K,p-Akt,and NOX4(P＜0.05,P＜0.01);increased pulmonary levels of SOD and GSH and protein expressions of E-cadherin and SIRT1(P＜0.05,P＜0.01);decreased ROS level,IL-1β,IL-6,TNF-α mRNA expressions and p-ERK,p-PI3K,p-Akt,NOX4 protein expressions in vitro(P＜0.05,P＜0.01);and increased SIRT1 protein expression in vitro as well(P＜0.01).CONCLUSION Being the main antitussive component of Suhuang antitussive capsule upon the PIC model,Sol A inhibits the inflammation via SIRT1/ERK signaling pathway and relieve the oxidative stress via PI3K/Akt/NOX4 signaling pathway.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.
Male ; Child ; Humans ; Homozygote ; Complement C3 ; Antibodies, Antinuclear ; DNA Copy Number Variations ; Sequence Deletion ; Interferons ; Lupus Erythematosus, Systemic/genetics* ; Antiviral Agents ; Endodeoxyribonucleases

OBJECTIVE: To compare the clinical efficacy of staged surgery on Sanders Ⅳ calcaneal fractures with soft tissue Ⅲ swelling. METHODS: The clinical data of 76 patients with Sanders type Ⅳ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageⅠclosed prying traction reduction and Kirschner wire fixation, stageⅡopen reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. RESULTS: All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups ( CONCLUSION Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type Ⅳ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.
Ankle Injuries ; Calcaneus/surgery* ; Female ; Foot Injuries ; Fractures, Bone/surgery* ; Humans ; Male ; Retrospective Studies

OBJECTIVE: To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. METHODS: A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI. RESULTS: Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups. CONCLUSIONS Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].

Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98％of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.

Gas chromatography (GC) is mainly used to detect the levels of short-chain fatty acids (SCFAs), but with the deepening of research,the drawbacks of GC have become more and more obvious in the fields of food,chemical engineering and clinical application. The analysis on existing research results showed that ultra performance convergence chromatography (UPC²) was appropriate for the analysis of lipid metabolism. The UPC² is a new kind of chromatographic separation technology developed in recent five years and the level of SCFAs is associated with the research on multiple diseases. Therefore,application of UPC² in the detection of SCFAs would be helpful for the scholars at home and abroad to carry out deeper researches,and also helpful to guide the treatment for various metabolic disorders. In this paper,the researches on SCFAs in recent ten years were reviewed; the shortcomings of GC and liquid chromatography (LC) in the detection of SCFAs were reviewed; the development process,basic characteristics and research status of UPC² at home and abroad were introduced; feasibility and innovation of UPC² in the detection of SCFAs were summarized. Pretreatment methods for UPC² application to the detection of SCFAs in feces or serum were collected; the problems that should be noticed during the process of sample pretreatment were pointed out; meanwhile, an research outlook on methodology of UPC² application in the detection of SCFAs was conducted. The effects of extracting solvent,mobile phase,and auxiliaryt solvent on chromatographic behavior as well as the physicochemical property, type and choice of UPC² chromatographic column were mainly discussed in this paper. In addition, the choices of basic modifier,acid modifier,and salinity modifier were briefly outlined, in order to provide efficient,simple,environmental,and economic detection technologies for the research on SCFAs, and provide better reference solutions for the rapid detection of massive clinical samples.