Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Objective:To investigate the protective effect of quercetin(QUE)on acute lung injury(ALI)rats with sepsis.Methods:Sixty male SD rats were randomly divided into 6 groups(n=10):Sham operation group(Sham),model group(CLP),QUE 25 mg/kg group,QUE 50 mg/kg group,QUE 100 mg/kg group and positive drug dexamethasone(DEX)group.Rats in each group were continuously treated for 7 days,and the survival rate was calculated;HE staining and lung wet-to-dry weight ratio(W/D)were used to evaluate the severity of lung injury;TUNEL staining was used to detect lung tissue apoptosis;levels of inflammatory factors,SOD and MDA were detected by the kits;Western blot was used to detect expressions of apoptosis-related proteins and phosphoryla-tion levels of PTEN,β-catenin,protein kinase B(AKT)and glycogen synthase kinase-3β(GSK-3β)in rat lung tissue.Results:Com-pared with CLP group,after QUE 50 mg/kg and 100 mg/kg treatment,survival rate of rats was significantly increased(P<0.05),the degree of inflammatory cell infiltration in lung tissue was reduced,lung injury score and W/D were reduced(P<0.05),apoptosis rate of lung tissue cells and expressions of apoptosis-related proteins were significantly decreased(P<0.05),levels of inflammatory factors were decreased(P<0.05),while the antioxidant capacity was enhanced(P<0.05),phosphorylation levels of PTEN and β-catenin were decreased,while phosphorylation levels of AKT and GSK-3β were increased(P<0.05).Conclusion:QUE protects rats from ALI with sepsis by inhibiting apoptosis,reducing inflammation and antioxidance,which mechanism may be related to PTEN/β-catenin and AKT/GSK-3β pathways.

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; Prognosis ; Stomach Neoplasms/pathology* ; China/epidemiology*

ObjectiveTo investigate the survival and adverse reactions of patients with unresectable cholangiocarcinoma after stereotactic body radiation therapy （SBRT）. MethodsA total of 27 patients with unresectable solitary cholangiocarcinoma without metastasis who underwent SBRT in The Fifth Medical Center of Chinese PLA General Hospital from February 2012 to July 2020 were enrolled. The prescribed dose to planning target volume was 42-60 Gy in 5-8 fractions， with 5-11 Gy/fraction. Among these patients， five patients were also treated with chemotherapy and transcatheter arterial chemoembolization. The 6-， 12-， 18-， and 24-month overall survival （OS） rates， progression-free survival （PFS） rates， and local control （LC） rates were used as the assessment indices for treatment outcome； Common Terminology Criteria for Adverse Events v.4.03 was used to evaluate adverse reactions； the Kaplan-Meier method was used to calculate OS， PFS， and LC rates. ResultsThe median follow-up time was 17 months. For all 27 patients， the 6-， 12-， 18-， and 24-month OS rates were 100%， 88%， 57.5%， and 47.9%， respectively； the 6-， 12-， 18-， and 24-month PFS rates were 74.1%， 58.6%， 47.9%， and 35.9%， respectively； the 6-， 12-， 18-， and 24-month LC rates were 96.3%， 91.9%， 84.8%， and 76.4%， respectively. No grade 3 or above toxic reactions were observed. Five patients were diagnosed with radiation-induced liver injury， but there was no death due to radiation-induced liver injury. ConclusionSBRT is safe and effective in the treatment of unresectable cholangiocarcinoma， with relatively high survival rate， PFS rate， and LC rate and low toxicity， and therefore， SBRT can be used as an alternative treatment method for patients with cholangiocarcinoma who are not candidates for surgery.

【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.

Objective:To study the clinical characteristics of different types of neonatal sepsis.Methods:From January 2012 to December 2019, neonates with confirmed sepsis from 5 neonatal centers of central-south China were reviewed. The neonates were assigned into early-onset sepsis (EOS) and late-onset sepsis (LOS) group, and the latter was further subgrouped into hospital-acquired LOS (hLOS) group and community-acquired LOS (cLOS) group. The etiological and clinical characteristics were analyzed. SPSS 26.0 was used for statistical analysis.Results:A total of 580 neonates were enrolled, including 286 (49.3%) in the EOS group and 294 (50.7%) in the LOS group. In LOS group, 147 were in hLOS group and 147 were in cLOS group. The gestational age and birth weight of hLOS group were significantly lower than the other two groups [(32.7±3.6) weeks vs. (37.1±3.7) weeks and (37.7±3.0) weeks, (1 810±717) g vs. (2 837±865) g and (3 024±710) g] ( P<0.05). The common pathogens in EOS and cLOS groups were coagulase-negative staphylococci and Escherichia coli, while Klebsiella pneumoniae was common in hLOS group. Carbapenems usage in the hLOS group was significantly higher than the other two groups [62.6% vs. 28.7% and 16.2%] ( P<0.05). Antibiotics duration in the hLOS group was longer than the other two groups [19 (14, 27) d vs. 15 (12, 20) d and 14 (12, 19) d] ( P<0.05). Conclusions:The clinical characteristics of neonatal sepsis vary among different types of infections, and it is necessary to establish appropriate prevention, control, diagnosis and treatment protocols.

Objective:Clinicopathological characteristics of neuroendocrine neoplasms are highly heterogeneous based on variable origins.Our study aims to explore the clinical features of rectal neuroendocrine neoplasm (RNEN).Methods:Patients with histologically diagnosed rectal neuroendocrine neoplasms were retrospectively analyzed between January 2012 and December 2020. Epidemiological characteristics, clinical manifestations, complete blood count, endoscopy findings, and pathological features were recorded and analyzed. T-test was used for measurement data analysis, Chi-square test was performed for classification data analysis, and Binary logistic regression was applied for analyzing risk factors of metastasis.Results:Among 172 patients, the male to female ratio was 107 to 65 with an average age of (52±12) years (16-77 years). Altered bowel habit was the most common initial symptom (58/172, 33.7%), followed by abdominal pain (36/172, 20.9%) and loss of body weight (27/172, 15.7%). One hundred and sixty-one cases were neuroendocrine tumors, 9 were neuroendocrine carcinomas and 2 were mixed neuroendocrine-non-neuroendocrine neoplasms. Most endoscopic presentations were polypoid lesions (147/172, 85.5%), mainly limited to mucosa (48/172, 27.9%) and submucosa (96/172, 55.8%). Twenty-nine patients developed lymph node invasion or distant metastasis at diagnosis. There were statistical difference of neutrophil-to-lymphocyte ratios (NLR) among groups with different tumor size (<10 mm vs. 10-20 mm vs.>20 mm, mean NLR 1.79±0.55 vs. 2.27±1.23 vs. 2.95±0.66, P<0.01. Compared with non-metastatic group, the metastatic group presented higher NLR(2.61±0.81 vs. 1.89±0.80, P<0.01). Tumor size (<10 mm vs. 10-20 mm vs.>20 mm, OR 1.00 vs. 2.10 vs. 5.25×10 9, P =0.001), invasion to bowel wall (mucosa vs. submucosa vs. muscularis vs. serosa invasion, OR 1.00 vs. 3.26 vs. 14.11 vs. 39.42, P=0.008), and NLR (NLR<2.25 vs. NLR≥2.25, OR 1.00 vs. 5.19, P =0.024) were risk factors for metastasis. Conclusion:Metastasis of RNEN is related with tumor size, degree of bowel invasion and NLR. High NLR is a poor prognostic factor of RNEN.

Sofosbuvir has ushered in a new era of hepatitis C treatment with its strong inhibition on the replication of hepatitis C virus, favorable safety profile and less interactions with other drugs. Sofosbuvir-based regimens have been included as the first-line therapies for the treatment of adults with chronic hepatitis C (CHC) in international guidelines. Available clinical trial data show that sofosbuvir with ribavirin and ledipasvir/sofosbuvir are highly efficacious and safe in CHC patients aged 3-17 years old; therefore, they can meet the unmet medical needs of adolescents and children with CHC in China. Furthermore, the pan-genotypic sofosbuvir/velpatasvir is being investigated in adolescents and children with CHC, which is expected to make the treatment in such patients more convenient upon approval.