The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

The outbreak of COVID-19 has spread quickly across 114 countries/territories/areas in six continents worldwide and has been announced as a pandemic by WHO. This study analyzed global COVID-19 epidemiological trends, examined impact of the pandemic on global health security, diplomacy, and social environment in China, and provided short- and long-term strategic policy recommendations for China’s subsequent preparedness and responses.

Objective To analyze the safety of laparoscopic splenectomy for traumatic splenic rupture.Methods The clinical data of 62 patients with traumatic splenic rupture treated by laparoscopic splenectomy in our hospital from Jan 2013 to Jan 2018 were retrospectively analyzed.Results All 62 patients successfully underwent laparoscopic surgery except for 1 case who was converted to open surgery.One case suffered from postoperative bleeding.There was no infection,serious pancreatic leakage and other major complications.The total amount of intraoperative bleeding was 1 600 ml on average,the average operation time was 135 min,the average splenectomy time was 55 min,and the average hospital stay was 12.5 d.Conclusion Laparoscopic splenectomy is a safe and reliable minimally invasive operation for traumatic splenic rupture.

Objective: To analyze vaccination situation of oral live attenuated rotavirus vaccine (LLR strain) among children from six provinces in China. Methods: In 2014, we selected 12 counties in Guangdong, Jiangsu, Chongqing, Jiangxi, Heilongjiang and Gansu provinces by using stratified cluster random sampling method and extract information of children born from January 1, 2008 to December 31, 2012 from Children's Immunization Information System. We investigated ten children of each birth cohort in each county by checking the vaccination certification, and a total of 606 children were investigated. A survey was conducted to check the information of the children's vaccination certification with the data of Children's Immunization Information System by questionnaire including the basic information (province, county, name, gender, birth date, etc) and the rotavirus vaccination (vaccination date, dose, etc) to analyze the rotavirus vaccination situation. Results: 340 of 606 children were male. There were 121, 124, 122, 119 and 120 children born in 2008-2012, respectively. The proportions of the first and the second dose of rotavirus vaccination were 32.8% (199) and 9.7% (59). The proportion of the third dose of rotavirus vaccination among children born between 2008 and 2010 was 3.5% (13) since children born in 2011 and 2012 did not reach the age of third dose vaccination. The proportion of the first dose of rotavirus vaccination in high, middle and low per capita disposable income areas was 45.0% (91), 37.7% (77) and 15.5% (31) respectively (χ²= 43.15, P<0.001). Among 199 children vaccinated with the first dose of vaccine, the vaccination age mainly concentrated in 2 to 21 months, of which the peak was 5 to 13 months (66.8%, 133). The intervals between 2 doses of vaccination were mainly from 12 to 13 months (42.4%, 25) among the 59 children who received at least 2 doses of vaccine. In the 13 children vaccinated with 3 doses, the intervals between the second and the third dose were 12 months (5). Of the 271 doses of rotavirus vaccine vaccinated during 2008-2014, 34.7% (94 doses) were vaccinated in June-August, 88 were vaccinated simultaneously with 18 other vaccines, accounting for 32.5% of the total. Of the 18 other vaccines, inactivated vaccines such as diphtheria vaccine (30 doses), Hib vaccine (14 doses), group A meningitis vaccine (10 doses) were predominant. Conclusion The proportion of rotavirus vaccination was low and the vaccination age was relatively late. The vaccination mode was different from the recommendation of WHO. It is recommended that routine immunization of rotavirus vaccines should be carried out in early-months of children.

Objective To evaluate the application value of whole exome sequencing (WES) in diagnosis of NDDs (neuro-developmental disorders) children.Metheod WES was used for the diagnosis of 35 unexplained NDD children, which admitted to the outpatient and ward of Children′s hospital affiliated to Capital institute of pediatric from November 2015 to November 2016.These children′s clinical data was collected detailedly.Using bioinformatics software tools combining with patient′s phenotype, the candidate genetic/genomic variants of these patients were identified from WES data.The final pathogenicity of genetic/genomic variants was interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG), meanwhile, the variants validation and co-separation analysis in the parents and their family members were performed by Sanger sequencing, real time-PCR and multiplex ligation-dependent probe amplification (MLPA).Results 14 pathogenic single nucleotide variants (SNVs) and three pathogenic copy number variations (CNVs) were detected in the 35 NDD children, the detection rate in this study is 48.6%.Among the 14 pathogenic SNVs, 11 of them are the definite NDD-related genes according to OMIM database (such as CHARGE syndrome, Wiedemann-Steiner syndrome, Cockayne syndrome, etc.), and six of them are de novo (6/11, 54.6%).Three pathogenic CNVs were identified from WES data, including two microduplications and one microdeletion.Meanwhile, a female child carrying a frame shift mutation in MECP2 was found and the germline mosaicism with low-frequency mutation of this site (8.4%) was confirmed by his father's sperm.Conclusions The diagnosis rate of WES in NDDs children is 48.6% in our small-sample study.In addition to pathogenic/likely pathogenic SNVs, CNVs can be detected successfully from WES data, which effectively improved the diagnosis yield in NDDs children.

Objective To analyze the clinical features and pathogenic gene mutation in a Chinese family with cerebro-oculo-facio-skeletal(COFS)syndrome,in order to summarize the relationship between phenotype and genotype.Methods The clinical data of the proband and his family members were collected.Genomic DNA from the proband and his parents were extracted by using standard procedures from the peripheral blood leukocytes.Next-generation sequencing was used to detect gene mutation in the patient with COFS syndrome.Sanger sequencing was applied to confirm the results.Results The proband,male,1 year and 3 months old,presented with microcephaly nystagmus,large ears,prominent nose,high arched palate,overhanging upper lip,micrognathia,widely set nipples,flexion contractures(especially involving the elbows and knees),failure to thrive,developmental retardation and feeding difficulty.His parents were normal phenotype.Two different heterozygous mutations c.1843G>T(P.G615W)and c.1996 C> T(P.R666W)were identified in the ERCC2 gene.The proband's father had the heterozygous mutation c.1843G>T(P.G615W)and his mother had the heterozygous mutation c.1996 C> T(P.R666W).Meanwhile,this heterozygous mutation c.1996 C> T(P.R666W)had been reported as a pathogenic gene mutation.Conclusions COFS syndrome is characterized by microcephaly,prominent nose,arthrogryposis and severe developmental delay.This is the first report on COFS syndrome patient in the mainland of China.The pathogenic gene mutations and gene status were identified through genetic studies.The result has laid the foundation for accurate genetic counseling and further prenatal diagnosis.

Objective To compare clinical efficacy between the situ secondary spleen pedicle amputation in laparoscopic splenectomy and open splenectomy for traumatic spleen rupture.Methods From January 2013 to June 2015 a total of 70 patients with splenic rupture undergoing splenectomy were devided into laparoscopic surgery (35 cases) and open surgery (35 cases) group.Clinical data included total intraoperative blood loss,the time spent on splenic artery ligation,total operation time,postoperative drainage volume,postoperative hemoglobin,platelet and albumin levels,time of anal exsufflation,hospital stay and postoperative complications.Results The average operation time in the OS group was shorter than that in LS group (P ＜ 0.05).However,LS group was better than the OS group in splenic artery ligation time,postoperative drainage volume,anus aerofluxus time,postoperative platelet count,postoperative albumin recovery,hospital stay and postoperative complications (all P ＜ 0.05).Conclusions The laparoscopic splenectomy by the amputation of in situ secondary spleen pedicle for traumatic spleen rupture has the advantages of a rapid recovery and a low postoperative complication.

Objective To evaluate ultrasound-guided methylene blue dyeing for radical liver segmental resection.Methods Liver segmental resection with uhrasound-guide methylene blue dyeing (UMD-SR) was performed in 16 cases, results were compared with 16 conventional liver segmental resection (CSR) retrospectively.Results All the operations under uhrasound-guided methylene blue dyeing were successfully carried out, among them, reverse dyeing was used in cases with segment Ⅳ, Ⅴ, Ⅷ resection.The blood loss in UMD-SR group was much less than CSR group(t =3.011 ,P =0.009) , at the cost of a longer operation time (t =5.423,P =0.000 07).There was no difference in the mortality and morbidity rates between two groups.Tumor recurrence rate was 6.25％ in UMD-SR group and 18.75％ in CSR group (x2 =0.133,P =0.285).Conclusions Ultrasound-guided methylene blue dyeing liver segmental resection can reduce the blood loss during operation, improve the safety of hepatectomy in case of hepatic carcinoma.

Objective To compare the clinical effect of platelet rich plasma and sodium hyaluronate in the treatment of knee osteoarthritis .Methods According to the different treatment methods ,100 patients with knee osteo-arthritis were divided into the control group ( for treatment of platelet rich plasma ) and study group ( for treatment of sodium hyaluronate),each group 50 cases.The treatment effect would be compared between two groups ,and the patients were scored knee joint active function using Lysholms score standard ,using visual analogue score method on patients with knee joint pain .Results The excellent and good rate had no significant difference between the study group(98.0%) and control group(94.0%)(P>0.05);The knee joint activity of study group (76.81 ±9.24) was significantly better than that of the control group (60.46 ±7.41),the difference was statistically significant (t =-9.76,P<0.05);the knee joint pain degree of the study group (1.91 ±0.88) was lower than that of the control group (3.58 ±0.85),the difference was statistically significant (t=9.65,P<0.05).Conclusion Platelet rich plasma and the knee joint injection of sodium hyaluronate in the treatment of osteoarthritis were able to effectively alle -viate knee joint pain ,activity limitation and other clinical symptoms ,improve the curative rate ,but the treatment effect of sodium hyaluronate is more remarkable ,which is worthy of promotion .