Objective To investigate the effects of valsartan on insulin resistance of type 2 diabetes in patients with Ⅰ hypertension.Methods Newly diagnosed 152 patients of type 2 diabetes with Ⅰ hypertension were randomly divided into treatment group and control group.The treatment group and control group undergone lifestyle changes( diet and adequate exercise) for two weeks.After that,the control group were given Diltiazem,while the treatment group were given valsartan,an angiotensin receptor blocker(ARB) drugs.Both groups were treated for 8 weeks.Fasting plasma glucose (FPG) and fasting plasma insulin (FINS) before and after treatment in both groups were determined.Homeostasis model assessment evaluation of insulin resistance index(HOMA-IR) and insulin sensitivity index (IAI) were carried out and compared between the two groups.Results After 8 weeks of treatment,HOMA-IR in the treatment group was significantly decreased compared with the control group ( P ＜ 0.01 ),while IAI was significantly increased( P ＜ 0.01 ).Conclusion Application of valsartan in type 2 diabetes mellitus with Ⅰ hypertension can significantly improve the level of insulin resistance.

Objective To assess the craniotomy in traumatic frontal sinus fracture cerebrospinal fluid( CSF) leaks.Methods Clinical data of 12 traumatic frontal sinus fracture CSF leaks from January 2010 to December 2014, who treated by craniotomy and conservation treatment was invalid were reviewed.Combined typical clinical presenta-tion and basicranial thin-layer computed tomography(CT),made qualitative diagnosis and localization.Craniotomy by bilateral coronary incision and epidural approach was performed.Repairation was mainly for the endocranium and the basicranium.Bone cement was used to reconstruct the osseous defect of the frontal sinus,and then with pedicle periosteal flap coverage.Dural defects was fixed with autogenous fascia.After operation,staying in bed and using anti-biotic for 7-14 days were required,while mannital or lumbar-drainage as needed.Results All 12 cases got posi-tive preoperative CT results.Craniotomy was performed,succeeded without reoperation.None of intracranial infection happened,while 1 case suffered from anosphrasia.Followed up for 3 -12 months, none CSF leaks relapsed. Conclusion Craniotomy by coronary incision,dispose the endocranium and the basicranium for the patients who suf-fered from frontal sinus fracture CSF leaks while conservation treatment is invalid,can obtain satisfied result.

Objective Improving the existed HPLC methods in order to detect the levels of global DNA methylation rapidly, stably and conveniently. Methods The HP1100 high performance liquid chrom-atographic (HPLC) system was used in this study. The analytic column was Macherey-Nagel (MN) EC 250/4.6 Nucleosil 100-5SA (250mm x 4. 6mm, 5u,m) cation exchange chromatographic column. We used 60mM acetic acid + 15% acetonitrile as mobile phase (adjust to pH =4. 6 by NaOH). The flow rate was 1. 0 ml/min, detective UV wavelength was set to 276 nm and column temperature was set to 28℃. The injection volume was 50μl. The global DNA methylation was expressed as 5mdC/(dC +5mdC) x 100%. Results Under these conditions, we can isolate dC and 5mdC completely in ten minutes. The level of leukocyte global DNA methylation in healthy people is (4. 389 ±0. 0159) %. Conclusions This method can determine the levels of global DNA methylation rapidly, and it can be widely applied in some laboratories.

Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.

Objective:To explore the safety of inactivated novel coronavirus vaccine inoculation and the fluctuating neutralizing antibody in patients with chronic hepatitis B (CHB).Methods:Retrospective and prospective epidemiological research methods were employed. 153 CHB patients who visited the Department of Infectious Diseases at the First Hospital of Shanxi Medical University from September 2021 to February 2022 were selected as the research subjects. Information on vaccination-related adverse reactions was collected. Colloidal gold immunochromatography was used to identify neutralizing antibodies in the body after 3-6 months of vaccination. Statistical analysis was performed using the χ2-test or Fisher's exact test. Results:The positive rates of neutralizing antibodies after inactivated novel coronavirus vaccine inoculation in 153 patients with CHB were 45.50%, 44.70%, 40.00% and 16.20%, respectively, at 3, 4, 5, and 6 months. The neutralizing antibody concentrations were 10.00 (2.95, 30.01) U/ml, 6.08 (3.41, 24.50) U/ml, 5.90 (3.93, 14.68) U/ml, and 1.25 (0.92, 3.75) U/ml, respectively. The difference was not statistically significant ( P>0.05) when the neutralizing antibody positivity rates in hepatitis B virus (HBV) DNA-negative and positive patients and HBeAg-negative and positive patients at different time points were compared. The overall incidence of adverse reactions following vaccination was 18.30%. Pain at the site of inoculation and fatigue were the main presentations, and no serious adverse reactions occurred. Conclusion:CHB patients, when inoculated with an inactivated novel coronavirus vaccine, can produce neutralizing antibodies, which can stay at certain levels for 3, 4, and 5 months. However, the neutralizing antibody level gradually decreases over time, and the decrease is remarkable at 6 months. So, it is recommended to boost vaccinations at an appropriate time. Additionally, the results of the study suggest that HBV replication status has little effect on the production of neutralizing antibodies in CHB patients with relatively stable liver function, which means the inactivated novel coronavirus vaccine has a good safety profile.

Objective:To retrospective analyze the epidemiology, clinical characteristics, treatment and prognosis in patients with coronavirus disease 2019 (COVID-19).Methods:A total of 278 patients with COVID-19 admitted to Guangzhou Eighth People′s Hospital from January 20 to February 10, 2020 were selected. The general demographic data, epidemiological data, clinical symptoms, laboratory examinations, lung CT imaging, treatment and prognosis were analyzed.Results:There were 130 male patients (46.8%) and 148 females (53.2%) with age (48.1±17.0) years and 88.8% patients between 20-69 years. Two hundred and thirty-six (84.9%) patients had comorbidities. Two hundred and eleven cases (75.9%) were common type. The in-hospital mortality was 0.4% (1/278). The majority (201, 72.3%) were imported cases mainly from Wuhan (89, 44.3%). The most common clinical manifestations were fever (70.9%) and dry cough (61.5%). In some patients, hemoglobin (10.4%), platelets (12.6%) and albumin (55.4%) were lower than the normal range. Other biochemical tests according to liver and function were normal, while lactic dehydrogenase (LDH) was elevated in 61 patients (21.9%), creatine kinase increased in 26 patients (9.4%). Prolonged activated partial thromboplastin time (APTT) was seen in 52 patients (18.7%), D-dimer higher than normal in 140 patients (50.4%), while 117 patients (42.1%) had elevated high-sensitivity C-reactive protein. Typical CT manifestations included single or multiple ground glass shadows especially in lung periphery in early disease which infiltrated and enlarged during progressive stage. Diffuse consolidation with multiple patchy density in severe/critical cases and even "white lung" presented in a few patients. Two hundred and forty-two patients (87.1%) received one or more antiviral agents, 242 (87.1%) combined with antibacterials, 191 (68.7%) with oxygen therapy. There were 198 patients (71.2%) treated with traditional Chinese medicine.Conclusions:COVID-19 could attack patients in all ages with majority of common type and low mortality rate. Clinical manifestations involve multiple organs or systems. Progression of the disease results in critical status which should be paid much attention.

The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing at home and abroad, and surgical treatment is still the main treatment. At present, subtypes of AEG mainly include Siewert and Nishi types. According to the location and stage of the tumor, the appropriate surgical approaches and methods are different, and with the application of minimally invasive technologies such as laparoscopy and robot assisted surgery, there is a certain impact on the occurrence of postoperative complications. However, the postoperative complications of AEG have not been explained in detail. This article will review and summarize the research progress of different surgical methods for AEG postoperative complications, in order to provide some reference for clinical treatment.

Objective:To compare the genotypes and phenotypes between the monozygotic twins via whole genome sequencing to further clarify the autosomal dominant inherited neurofibromatosis type 1 (NF1) variants related to congenital pseudarthrosis (CP).Methods:According to the diagnostic criteria of congenital tibial pseudarthrosis and the clinical diagnostic criteria of NF1, two pairs of monozygotic twins with NF1 were included. Both were female and only one of each pair had congenital pseudarthrosis. The other did not have congenital pseudarthrosis. Whole genome sequencing was performed using the peripheral blood of the two pairs of monozygotic twins. Customized bioinformatics analysis was then performed to identify single nucleotide variants (SNVs), short insertion deletion variants (InDel), copy number variants (CNVs), and structural variants (SVs). Classified the variants according to the American College of Medical Genetics and Genomics (ACMG) and ClinGen criteria. The germline variants within the monozygotic twins were compared to identify the CP patients' unique variants. The shared pathogenic or likely pathogenic germline variants between the unique variants in the CP patients from the twins were also analyzed. Further, the identified disease-causing variants were validated by Sanger sequencing in the family of the twins and their parents. Finally, the genotypes and phenotypes regarding the pathogenic variants of the NF1 gene among the twins were characterized. Results:Both the two monozygotic twins were identified pathogenic variants in the NF1 gene. One with c.3047_3048del (p.Cys1016SerfsTer4), and the other with c.4267A>G (p.Lys1423Glu). By Sanger sequencing validation in family quads, the two CP patients and their siblings harbored de novo heterozygous variants of the NF1 gene. In addition to the NF1 gene, no other genes were identified pathogenic or likely pathogenic variants uniquely in the CP patients compared with their twin sisters, as well as SVs and CNVs. In addition, by analyzing the rare and damaging variants in the two CP patients from the two twins, they had no overlapping genes against the SNVs, InDels, SVs, or CNVs. Conclusion:Whole genome sequencing revealed that both the two monozygotic twins with NF1 were detected pathogenic variants of gene NF1. No other pathogenic variants specific to the CP patients among the twins were identified. The two CP patients shared no other common genes from the detected likely pathogenic variants.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

OBJECTIVE To provide reference for the management of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis. METHODS The clinical pharmacist participated in the treatment of a thrombocytopenia patient with atrial fibrillation and atherosclerosis， and analyzed the causes of thrombocytopenia according to the patient’s medical history and laboratory examination results. At the same time， the risk of thrombosis-bleeding was evaluated according to the relevant guidelines， and the clinicians were assisted in formulating individual antithrombotic therapy plan and pharmaceutical care plan for the patient. The literature on antithrombotic therapy related to thrombocytopenia was collected and analyzed by retrieving CNKI. RESULTS Thrombocytopenia was considered as primary thrombocytopenia in this patient， and the main risk of bleeding was age ≥65 years old， bleeding tendency， and combined use of antithrombotic drugs. After the clinical pharmacist assessed the risk of thrombosis and bleeding， the clinician was recommended to give full dose of Bemiheparin sodium injection + Dronedarone hydrochloride tablets + Metoprolol succinate sustained-release tablets. In view of thrombocytopenia， the clinician gave Compound zaofan pill， Caffeic acid tablet and Sheng xuexiaoban capsule， but the patient developed diarrhea after the medication. The clinical pharmacist suggested stopping Sheng xuexiaoban capsule， and the clinician adopted the clinical pharmacist’s suggestion. When the patient was discharged from hospital， the clinical pharmacist suggested that the antithrombotic therapy plan for discharge was anticoagulation alone or selective anticoagulation. The clinician chose selective anticoagulation treatment considering that the patient’s current thrombocytopenia， urinary occult blood （+） and fecal occult blood were weakly positive， and ordered the patient to take Metoprolol succinate sustained-release tablets + Atorvastatin calcium tablets at discharge. Literature analysis showed that the causes of thrombocytopenia of patients with thromboembolism mainly included heparin induced-thrombocytopenia， immune thrombocytopenia， etc. All patients were improved after symptomatic treatment. CONCLUSIONS By participating in the management of antithrombotic therapy for the thrombocytopenia patient with atrial fibrillation and atherosclerosis， clinical pharmacists can help effectively control the patient’s condition and ensure the safety and effectiveness of drug use.