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

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Objective:To comparatively study the similarities and differences between the clinical, pathological, and risk factors of advanced fibrosis in men and women with non-alcoholic fatty liver disease (NAFLD).Methods:267 patients with NAFLD diagnosed by liver biopsy were retrospectively included, and were divided into male and female groups. The difference of clinical and pathological indexes were compared between the two groups. The measurement data were in accordance with normal distribution. The comparison between the two groups was performed by independent sample t-test. The non-parametric test was used for non-normal distribution. The classification data were expressed as a percentage, and the chi-square test was used for comparison between groups. Logistic regression analysis was used to analyze the risk factors.Results:The age of onset of NAFLD was significantly lower in male than female patients ( P < 0.01). There was no statistically significant difference between the male and female groups in terms of body mass index and the prevalence of type 2 diabetes ( P > 0.05). Biochemical index: The levels of alanine aminotransferase, albumin, total bilirubin and uric acid were significantly higher in male than female patients ( P < 0.01). Liver pathology: The proportion of ballooning degeneration was significantly lower in male than female patients ( P < 0.01). There was not statistically significant difference between the two groups in the proportion of steatohepatitis score, non-alcoholic steatohepatitis (52.0% vs. 61.5%, P = 0.283) and advanced liver fibrosis (14.3% vs. 17.8%, P = 0.162). Thrombocytopenia was a common independent risk factor for advanced stage liver fibrosis ( OR = 0.984, 0.978~0.989, P < 0.01). Type 2 diabetes was only an independent risk factor for advanced stage liver fibrosis in men ( OR = 6.557, 1.667~25.782), P < 0.01). Elevated AST was only an independent risk factor for advanced stage liver fibrosis in women ( OR = 1.016, 1.003~1.028, P = 0.012). Conclusion:In NAFLD patients, there are some clinical and pathological differences between genders. Platelets are a common predictor of advanced liver fibrosis in men and women. Type 2 diabetes in men and elevated aspartate aminotransferase in women can be regarded as independent risk factors for advanced liver fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

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.

Objective To investigate the effect of midazolam on inflammatory response in patients with moderate and severe craniocerebral injury and its protective effect on the brain and mechanism.Methods A prospective study was conducted.One hundred and twenty patients with moderate and severe craniocerebral injury admitted to the Intensive Care Unit (ICU) of Jiangsu Subei Peoples' Hospital from April 2013 to July 2016 were enrolled,and they were divided into a conventional treatment group (58 cases) and a midazolam group (62 cases) according to the random number table method.Both groups were given conventional western medicine treatment,and in cases with surgical indications,operations were performed;in midazolam group,additionally intravenous injection of midazolam 2-3 mg was given firstly,and then continuous intravenous infusion of the drug 0.05-0.10 mg· kg-1· h-1 was applied by a pump,and in operative patients,the above management was given 3 hours after operation.The mean arterial pressure (MAP),heart rate (HR),Riker sedation agitation score (SAS) and electroencephalogram bispectral index (BIS) were measured before and after treatment for 24,48 and 72 hours,respectively.The levels of interleukin-6 (IL-6) and soluble nerve chemotactic protein (sFkn) in plasm and cerebrospinal fluid (CSF) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA) at each time point;the incidence of epilepsy and 28-day mortality were recorded.Results Before and after treatment,the MAP and HR in the two groups of patients were stable,the difference being not statistically significant (both P ＞ 0.05).Compared with those before treatment,after treatment the SAS score and BIS in two groups of patients were gradually decreased,and at 72 hours reached the lowest levels (SAS score:conventional treatment group was 3.8 ± 1.0 vs.5.7 ± 2.0,midazolam group was 3.6 ± 0.9 vs.5.8 ± 1.7;BIS:conventional treatment group was 69± 12 vs.82± 12,midazolam group was 72± 15 vs.82± 12,all P ＜ 0.05),but there were no significant differences between the two groups (all P ＞ 0.05),suggesting that the two groups had achieved the desired goal of sedation.ELISA results showed:compared with those before treatment,after treatment for 24 hours,the CSF IL-6,sFkn and plasm sFkn levels were temporarily increased in short term,and then showed a tendency of gradually decreasing,and the plasm IL-6 presented persistently descending in the conventional treatment group,while in the midazolam group,since 24 hours after treatment,each index showed a trend of decrease and continued to 72 hours.After treatment at each time point,the CSF and plasm levels of IL-6 and sFkn were significantly lower in midazolam group than those of the conventional treatment group,and reached to the minimal levels at 72 hours [CSF:IL-6 (ng/L) was 251.6 ± 145.7 vs.347.3 ± 146.4,sFkn (ng/L):289.7 ± 79.3 vs.423.6 ± 132.8;plasm:IL-6 (ng/L) was 54.4± 27.3 vs.85.6 ± 41.8,SFkn (ng/L):919.9±426.3 vs.1 199.4 ± 414.8,all P ＜ 0.05].The incidence of epilepsy in the midazolam group was obviously lower than that in the conventional treatment group [1.61％ (1/62) vs.10.34％ (6/58),P ＜ 0.05],but there was no significant difference between midazolam group and the conventional treatment group in the 28-day mortality [11.29％ (7/62) vs.10.34％ (6/58),P ＞ 0.05].Conclusion Midazolam can reduce the incidence of epilepsy in patients with moderate and severe traumatic brain injury,and its brain protective effect may be related to the decrease of CSF and plasm IL-6 and sFkn levels.

In order to investigate the pathogens associated with a clustered event of fever occurred in a kindergarten in Fuzhou,Fujian Province,samples were collected from pediatric cases in the kindergarten and screened for various possible viral agents by real-time PCR.Of 10 respiratory specimens,7 were positive of human adenovirus (HAdV).The positive samples were inoculated into HEp-2 cell-lines for viral isolation.The PCR products of the hypervariable regions of Hexon gene were sequenced,followed by BLAST searches for viral type identification.In comparison with the strains prevalent in domestic or abroad in recent years,the deduced amino acid sequences showed no amino acid mutation in the hypervariable regions of Hexon.Combined with clinical manifestation and field epidemiological data,human adenovirus type 7 could be confirmed as the pathogen linked to the clustered event.

OBJECTIVETo compare the effect of three cannulated screws and dynamic hip screw (DHS) combined with antirotation screw in treating patients with comminuted fractures of femoral neck.

METHODSFrom January 2008 to December 2012,67 patients with comminuted fractures of femoral neck were treated with three cannulated screws or DHS combined with antirotation screw. Among them, 36 patients were treated with DHS combined with antirotation screw including 24 males and 12 females with an average of 43.7 years old ranging from 22 to 58 years old; 31 patients were treated with three cannulated screws including 22 males and 9 females with an average of 43.0 years old ranging from 24 to 56 years old. The incision size, operation time, blood loss, blood transfusion rate, postoperative hospital stay, walking time, weight-bearing time, union time, incidence of complication were recorded and compared between two groups, and functional outcomes were evaluated by Harris scoring.

RESULTSAll incision healed at stage I. The differences in operation time, blood loss, blood transfusion rate and postoperative hospital stay between two groups were not significant (P > 0.05). Incision size of DHS group (5.00 ± 0.86) cm was larger than that of cannulated screw group (3.30 ± 0.57) cm (P < 0.01). All patients were followed up more than one year, and the follow-up time showed no significant difference between two groups (P > 0.05). Walking time of DHS group (19.0 ± 3.5) d was less than that of cannulated screw group (37.0 ± 6.3) d (P < 0.01. Partial and full weight-bearing time of DHS group (23.0 ± 7.0) d and (138.0 ± 13.0) d was less than that of cannulated screw group (38.0 ± 5.7) d and (164.0 ± 12.0) d (P < 0.01). Union time of DHS group (151 ± 11) d was less than that of cannulated screw group (162 ± 11) d (P < 0.01). Harris hip score of DHS group (91.0 ± 5.7) was higher than that of cannulated screw group (85.0 ± 12.0) (P < 0.01). No significant differences were found in the incidence of postoperative complications between two groups (P > 0.05).

CONCLUSIONThe DHS combined with antirotation screw is superior to three cannulated screws for treatment of comminuted fractures of femoral neck due to earlier weight-bearing, faster fracture healing and better hip function

Adult ; Bone Screws ; Female ; Femoral Neck Fractures ; surgery ; Follow-Up Studies ; Fracture Fixation, Internal ; adverse effects ; methods ; Fractures, Comminuted ; surgery ; Humans ; Male ; Middle Aged