Interleukin (IL)-35 is a new member of IL-12 family who is secreted by T regulatory cells to strongly sup?press immuno reaction directly or indirectly. There is a growing interest in the using IL-35 as a potential therapy for chronic in?flammatory , cancer and autoimmune diseases. Here we reviewed IL-35 and its function as a mediator of suppression.

Objective:To explore the relationship between metabolic acidosis and cardiac valve calcification in maintenance hemodialysis (MHD) patients in the Pearl River Delta Region.Methods:Patients on MHD greater than 3 months who were treated in 10 blood purification centers in the Pearl River Delta Region from July 1 to September 30, 2019 were selected for this multicenter cross-sectional study. Based on a Doppler ultrasound, MHD patients were further divided into non-valve calcification group and valve calcification group. The demographics data, frequency of dialysis, blood pressure, single pool Kt/V(spKt/V), dialysis medications and laboratory data were collected and compared. Spearman correlation analysis was used to analyze the correlation between serum carbon dioxide combining power (CO 2CP) and cardiac valve calcification. Multivariate logistic regression model was used to analyze the influencing factors of cardiac valve calcification. Results:A total of 664 MHD patients were included in this study, with age of (57.0±14.2) years old and dialysis age of 43.0 (22.3, 71.7) months, including 395 males (59.5%) and 269 females (40.5%). Among them, there were 119 patients (17.9%) with diabetes and 186 patients (28.0%) with dialysis 2 times per week. There were 329 patients (49.5%) in the valve calcification group, and 335 patients (50.5%) in the non-valve calcification group. Compared to those in non-valve calcification group, valve calcification group had longer duration of dialysis, higher proportion of patients with dialysis 2 times per week, higher levels of diastolic blood pressure, fasting blood glucose, intact parathyroid hormone and ferritin, higher proportion of patients with blood CO 2CP<19 mmol/L (median CO 2CP), higher proportion of patients on usage of calcium channel blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, α-receptor blocker, β-receptor blocker, calcitriol and lanthanum carbonate (all P<0.05), while the levels of spKt/V, hemoglobin, serum CO 2CP, corrected calcium, blood phosphorus, blood alkaline phosphatase, albumin, total cholesterol, triacylglycerol, low-density lipoprotein, high-density lipoprotein, transferrin saturation, and the proportion of patients on usage of sevelamer and cinacalcet were lower (all P<0.05). Spearman analysis showed significant negative correlation between serum CO 2CP and valve calcification ( rs=-0.697, P<0.001). Multivariate logistic regression analysis showed that dialysis performed twice a week ( OR=2.789, 95% CI 1.232-6.305, P=0.014), blood total cholesterol ( OR=1.449, 95% CI 1.014-2.071, P=0.042), CO 2CP<19 mmol/L ( OR=22.412, 95% CI 10.640-47.210, P<0.001) were the influencing factor of valve calcification in MHD patients. Conclusions:MHD patients with cardiac valve calcification have significant acid loading. Metabolic acidosis is an independent influencing factor for cardiac valve calcification in MHD patients.

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 establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

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 conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.