Objective To investigate the effect of Shanzha Xiaozhi Capsules (SXC) on body weight, metabolic indexes, body fat accumulation and distribution of obesity patients with phlegm-dampness constitution. Methods Fifty obesity patients with phlegm-dampness constitution were randomized into control group and medicine group, 25 cases in each group. The control group was given lifestyle instructions for diet and exercises, and the medicine group was treated with SXC orally besides the instructions for lifestyle. The treatment for both groups covered 12 weeks. Before and after treatment, we observed the outcomes including scores of phlegm-dampness, body weight, waist circumference, hip circumference, blood pressure, fasting blood glucose, serum lipid profile, urine acid, body fat accumulation and distribution, and visceral fat accumulation. Results(1) The scores of phlegm-dampness were decreased significantly in both groups after treatment (P<0.05 or P<0.01), and the decrease was obvious in the medicine group(P<0.01).(2) Body weight and BMI were decreased significantly in both groups after treatment(P<0.01), and the decrease was obvious in the medicine group(P<0.05). Waist circumference was decreased significantly in the medicine group(P <0.05) but stayed unchanged in the control group(P>0.05). Hip circumference was decreased significantly in both groups(P <0.05 or P<0.01) , but the difference between the two groups was insignificant(P>0.05).(3) Systolic pressure and diastolic pressure were decreased significantly in both groups (P<0.01). But the difference of blood pressure decrease between the two groups was insignificant(P > 0.05).(4) Fasting blood glucose, 2-hour blood glucose after oral glucose tolerance test, serum lipid profile and urine acid remained unchanged in both groups after treatment (P>0.05). (5) The general body fat accumulation of both groups was decreased significantly after treatment (P <0.05 or P<0.01), and the decrease was obvious in the medicine group(P<0.01). Body fat accumulation in legs, trunk and gynoid region were decreased significantly in both groups after treatment(P<0.05 or P<0.01), but the difference of fat accumulation decrease between the two groups was insignificant(P>0.05). Waist fat accumulation had no significant decrease in the control group (P > 0 . 05), but was decreased in the medicine group (P<0.01). Visceral fat accumulation was decreased significantly in both groups after treatment(P<0.01), and the decrease was obvious in the medicine group (P<0.01). Conclusion In addition to its contribution to body weight loss, SXC also contribute to the reduction of visceral fat accumulation in obesity patients with phlegm-dampness constitution .

Objective To investigate the effects of Shanzha Xiaozhi capsule on body weight, metabolic index, percentage and distribution of body fat in obese patients with dampness-heat constitution. Methods A total of 60 obesity patients with dampness-heat constitution were enrolled in this study and randomly categorized into the control group ( n=30) and treatment group (n=30). Control group was given the diet and exercise regime, and treatment group was given Shanzha Xiaozhi capsule based on the same diet and exercise regime for 12 weeks. Scores of dampness-heat, body weight, waist circumference, hip circumference, blood pressure, blood glucose, serum lipid profile, urine acid (UA), fasting plasma insulin, serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, adiponectin, lipopolysaccharide (LPS), percentage and distribution of body fat were measured before and after treatment. Results (1) Data of scores of dampness-heat and diastolic blood pressure were significantly decreased after treatment in drug group. The above indexes and hip circumference were significantly decreased after the treatment in treatment group compared with those of control group ( P<0.05). (2) The triglyceride (TG), UA, insulin, HOMA-IR, LPS and IL-1βwere significantly decreased after the treatment in treatment group than those of control group, while there were no significant differences in fast blood glucose (FBG), 2 h postprandial plasma glucose (2 hPG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), TNF-α, IL-6 and adiponectin between two groups. (3) The percentage of visceral fat was significantly decreased in treatment group than that of control group. There were no significant differences in fat changes of limbs and buttocks between two groups. Conclusion Shanzha Xiaozhi capsule can decrease body weight and visceral fat content, reduce insulin resistance, and improve chronic inflammation state in obese patients with dampness- heat constitution.

Objective To detect miR-34a expression in pancreatic cancer tissue and BxPC3 cells,determine the target genes and analyze the correlation of the expression of miR-34a and its target genes with clinicopathological parameters in pancreatic cancer as well as the influence on the proliferation and migration abilities of BxPC3 cells.Methods c-MET 3'UTR dual-luciferase reporter vectors cloned wild-type and mutant c-MET 3'UTR to validate that c-MET was the target gene of miR-34a,respectively.Liposome was used to establish miR-34a overexpressing BxPC3 cells (miR-34a group) and c-MET downregulating BxPC3 cells (c-METsi group).qPCR,Western blot and IHC was used to measure the mRNA and protein expression of miR-34a and c-MET.The cell viability and migration ability of miR-34a overexpressing BxPC3 cells was assessed by CCK-8 and transwell assay.Results In miR-34a group,the 3'UTR of wild-type c-MET was obviously downregulated compared with that of control group [(65.00 ± 4.04) ％ vs 100％,P =0.00131)],but no statistical difference was found between two mutant groups,which proved that c MET was the target gene of miR-34a.The expression level of miR-34a was significantly down-regulated in cancer tissues compared to adjacent normal tissues by an average fold change of 1.92,and the difference was statistically significant (P =0.003).Compared with control group,c-MET mRNA and protein expression was obviously decreased in miR-34a group (0.045 ±0.003 vs 0.085 ±0.001,0.400±0.058 vs 1.133 ±0.120).After 4-day culture,the cell viability of miR-34a group and c-METsi group was obviously decreased (P =0.0012;P =0.0001),the transmembrane cells was also obviously decreased(231 ± 12 vs 351 ± 16,P =0.0039;259 ±7 vs 351 ± 16,P=0.0066),and the differences were statistically significant.miR-34a overexpression and c-MET positively expression in pancreatic cancer were significantly associated with TNM stage and tumor differentiation (P ＜0.001),and the expression of c-MET negatively correlated with miR-34a (P ＜0.001).Conclusions miR-34a was lowly expressed in pancreatic cancer,and its tumor suppressive activity may be partly through inhibiting c-MET.Overexpressing miR-34a or inhibiting c-MET may be new targets for the diagnosis and treatment of pancreatic cancer.

Objective To investigate the clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein (PV)-superior mesenteric vein (SMV) shunting for complicated pancreatic head tumors.Methods The retrospective cohort study was conducted.The clinicopathological data of 91 patients with pancreatic head cancer who were admitted to the Changhai Hospital of Navy Medical University from February 2011 to December 2016 were collected.Among 91 patients undergoing pancreaticoduodenectomy combined with vascular resection and reconstruction,27 using artery first approach and PV-SMV shunting and reconstruction were allocated into the PD-PVR group,23 using conventional approach were allocated into the PD-CVR group,and 41 receiving pancreaticoduodenectomy with vascular resection were allocated into the PD-SVR group.Observation indicators:(1) comparison of intra-and post-operative situations among groups;(2) comparison of postoperative pathological results among groups;(3) comparison of postoperative survival among groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2017.Comparisons among groups of count data were done by the chi-square test or Fisher exact probability.Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA,and pairwise comparison was done using the LSD method.Measurement data with skewed distribution were described as M(Q),comparison among groups was analyzed using the Kurskal-Wallis rank sum test,and pairwise comparison was done using the paired comparison with adjusted P value.Ordinal data were compared using the nonparametric test.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Comparison of intra-and post-operative situations among groups:operation time,time of hepatic inflow occlusion,volume of intraoperative blood loss,cases with intraoperative blood transfusion,length of PV or SMV removal,cases with vascular grafts,grading 1,2,3,4 and 5 of Clavien-Dindo classification of postoperative complications and duration of hospital stay were respectively (274±36)minutes,(22±7)minutes,1 661 mL (110 mL,3 800 mL),20,(5.6±1.4)cm,6,11,1,1,1,1,(20±7)days in the PD-PVR group and (281±41)minutes,(27±5)minutes,1 888 mL (176 mL,4 162 mL),18,(5.4±1.5) cm,3,1,8,2,0,0,(21±7)days in the PD-CVR group and (201± 36)minutes,(16±6)minutes,1052 mL (74 mL,3 926 mL),17,(3.2±2.0) cm,5,15,2,3,1,1,(13± 6)days in the PD-SVR group,with statistically significant differences among groups (F=37.060,34.530,x2=13.771,14.015,F=32.260,x2 =39.309,F =19.880,P＜0.05).Patients with postoperative complications were improved by symptomatic and supporting treatment.(2) Comparison of postoperative pathological results among groups:mnaximum tumour dimension was respectively (3.6± 1.3) cm,(4.0± 1.3) cm and (2.6± 1.3) cm in the PD-PVR,PD-CVR and PD-SVR groups,with a statistically significant difference among groups (F =7.845,P＜0.05).Cases with high-differentiated,moderate-differentiated and low-differentiated tumors of tumor differentiation,staging Ⅱ A and Ⅱ B of tumor staging,nerve invasion,positive lymph node,positive resection margins in neck of pancreas,bile duct and SMV were respectively 0,13,14,17,10,17,21,0,0,0 in the PD-PVR group and 1,12,10,10,13,15,19,1,0,0 in the PD-CVR group and 1,29,11,17,24,30,29,2,1,1 in the PD-SVR group,with no statistically significant difference among groups (x2 =4.122,3.306,0.902,1.214,P＞0.05).(3) Comparisons of postoperative survival among groups:of 91 patients,52 were followed up for 3.0-69.3 months,with a median time of 18.0 months and follow-up rate of 57.1％ (52/91),including 16 in the PD-PVR group and 14 in the PD-CVR group and 22 in the PD-SVR group.The median survival time,1-,2-and 3-year overall survival rates in 52 patients were respectively 16.6 months,63.5％,35.7％ and 26.8％.The survival time in the PD-PVR,PD-CVR and PD-SVR groups were respectively 12.3 months (3.9-69.3 months),15.0 months (3.0-63.3 months) and 20.0 months (6.0-65.2 months),with a statistically significant difference in survival among groups (x2=6.201,P＜0.05),and between PD-PVR and PD-SVR groups (x2 =4.412,P＜0.05).There was no statistically significant difference in survival between PD-PVR and PD-CVR groups (x2 =0.001,P＞0.05).Conclusion Pancreaticoduodenectomy using artery first approach and PV-SMV shunting and reconstruction for complicated pancreatic head tumors can reduce the time of hepatic inflow occlusion,it also contributes to the risk control of surgery for complicated pancreatic tumors,increases surgical safety and improves patients' prognosis.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia