Objective:To overview the systematic reviews/meta analysis of the treatment of external therapy of TCM for gastroesophageal reflux disease (GERD).Methods:Systematic reviews/meta analysis of the treatment of external therapy of TCM for GERD were retrieved from CNKI, Wanfang Data, VIP, CBM, PubMed, Embase and Cochrane Library databases from the establishment of the databases to 31st, December 2022. The AMSTAR 2 tool, PRISMA 2020 reporting specifications, and GRADE guidelines were used to evaluate the methodological quality, reporting quality, and evidence quality of the included literature. A multiple evaluation was performed in six dimensions: year of publication, type of study design, methodological quality score, reporting quality score, degree of homogeneity, and risk of publication bias evaluation.Results:A total of 9 systematic reviews/meta analysis were included, of which 1 was of low quality methodological quality and 8 was of very low quality. GRADE guidelines evidence quality grading results showed 33 outcome indicators, 9 of which were with moderate evidence, 21 of which were with low evidence, and 3 of which were with very low evidence. 9 articles had reporting quality scores ranging from 16 to 24, of which 1 report was relatively complete and 8 had some deficiencies. The rank mean scores of multiple evaluations indicated that 2 articles were of high quality and 1 article was of poor quality.Conclusions:The quality of evidence for the treatment of external therapy of TCM for GERD is intermediate in terms of improving the cure rate and reducing adverse effects, and is recommended for clinical use. However, the methodological quality and reporting quality of the current systematic reviews/meta analysis of the treatment of external therapy of TCM for GERD need to be improved, and users of the evidence ought to use the above evidence with caution for decision making.

Objective:To study the clinical results of personalized surgical treatment for portal hypertension based on portal venous hemodynamics.Methods:A retrospective study was performed on patients with portal hypertension who underwent surgical treatment from January 2016 to December 2020 at the People’s Hospital of Ningxia Hui Autonomous Region and Wuhai People’s Hospital. Of 229 patients included into this study, there were 156 males and 73 females, with age of (4±11) years old. Portal vein CT and ultrasound doppler examination were performed preoperatively and portal vein manometry and ultrasound doppler examination were performed intraoperatively to evaluate portal venous hemodynamics. Based on the evaluation results, different surgical treatments were adopted. Postoperative complications and results of the operations were recorded. Long-term outcomes were evaluated by the rate of recurrence of gastroesophageal varices which was classified as disappearance, mild, moderate and severe according to endoscopic findings.Results:All the 229 patients completed the operations successfully. All together 13 operative treatments were used: (1) simple splenectomy ( n=11); (2) devascularization ( n=176), including 86 patients with splenectomy combined with extensive devascularization, 44 patients with splenectomy combined with selective devascularization and with preservation of paraesophageal veins, 39 patients with splenectomy combined with selective devascularization and reconstruction of spontaneous portosystemic shunt (34 patients with selective devascularization and reconstruction of spontaneous gastrorenal shunt and 5 patients with selective devascularization and reconstruction of spontaneous splenorenal shunt), 4 patients with secondary devascularization for variceal recurrence and 3 patients with devascularization and preservation of spleen; (3) shunt procedures were performed in 42 patients including 21 patients with splenectomy combined with coronary renal shunt, 11 patients with splenectomy combined with coronary-caval shunt, 6 patients with distal splenorenal shunt, 2 patients with proximal splenorenal shunt combined with devascularization, 1 patient with right gastroepiploic vein-inferior vena cava shunt and 1 patient with trans-inferior mesenteric vein coronary renal shunt. There were no operative deaths. The Clavien-Dindo grade 3 and above postoperative complication rate was 6.6% (15/229). Two hundred and eight patients were followed up for 6-60 months, with a median follow-up of 38 months. Severe recurrent varices were found in 21 patients (10.1%, 21/208), with 5 patients (2.4%, 5/208) presented with variceal bleeding. The rate of severe varices after selective shunting and selective devascularization by reconstructing the spontaneous portosystemic shunt (4.2%, 3/72) was significantly lower than that of the other devascularization procedures (13.7%, 17/124)(χ 2=4.53, P=0.033). Conclusion:Better clinical results were achieved by selecting the appropriate surgical procedures based on portal venous hemodynamic characteristics of patients. Selective shunting and selective devascularization by reconstructing the spontaneous portosystemic shunts significantly reduced the recurrence rate of severe varies.

Objective:To evaluate the preventive effect of proximal splenic vein ligation after splenectomy on the splenic vein originated portal vein thrombosis (PVT) in portal hypertension.Methods:The clinical data of 94 patients of portal hypertension who had received splenectomy were retrospectively analysed. The proximal splenic vein was ligated in 36 cases during pericardial devascularization and coronary renal shunt with splenectomy. The other 58 cases who had received pericardial devascularization without proximal splenic vein ligation served as control. All of the patients in both groups were given heparin infusion postoperatively through the catheter which was placed in the right gastroepiploic vein during operation. CT portal veinography was performed at the 7th-14th postoperative day for detection of PVT.Results:None of the PVT occurred in the splenic vein ligation group. In the control group, PVT occurred in 22 cases(38%) and splenic vein thrombosis occurred in all the 58 cases (100%). PVT incidence between the two groups is significantly different (0 vs. 38%, χ 2=17.828, P<0.05). Conclusions:Ligation of the proximal splenic vein during splenectomy can effectively prevent the postoperative splenic vein originated PVT in portal hypertension.

Objective To summarize the changing rules of free portal pressure (FPP) after splenectomy combined with pericardial devascularization and investigate its influencing factors.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 55 patients with portal hypertension who were admitted to the People's Hospital of Ningxia Hui Autonomous Region from January 2016 to September 2018 were collected.There were 39 males and 16 females,aged from 17 to 67 years,with a median age of 46 years.FPP was measured using CT portal vein angiography before splenectomy and intraoperative manometry after cantheterization to the right gastroepiploic veins.Observation indicators:(1) comparison between intraoperative and postoperative FPP;(2) dynamic changes of FPP at the seventh postoperative day;(3) comparison of FPP before and after Valsalva manoeuvre;(4) relationship of FPP with mean arterial pressure and heart rate.Measurement data with normal distribution were represented as Mean ±SD.Repeated measurement data were analyzed using repeated ANOVA.Paired data were analyzed by the paired t test.The linear correlation analysis was done for relevance.Results (1) Comparison between intraoperative and postoperative FPP:55 patients underwent open splenectomy combined with pericardial devascularization.The FPP before splenectomy,after splenectomy combined with pericardial devascularization intraoperatively,at the first and the seventh day postoperatively was (34±6)cmH2O (1 cmH2O=0.098 kPa),(28±6)cmH2O,(34±5)cmH2O and (30±5)cmH2O,respectively,showing a statistically significant difference (F=43.23,P＜0.05).The FPP before splenectomy was statistically significant different from the FPP after splenectomy combined with pericardial devascularization intraoperatively,at the first and the seventh day postoperatively,respectively (P ＜ 0.05).The FPP after splenectomy combined with pericardial devascularization intraoperatively was statistically significant different from the FPP at the first and the seventh day postoperatively,respectively (P＜0.05).There was a statistically significant difference between FPP at the first and the seventh day postoperatively (P ＜ 0.05).(2) Dynamic changes of FPP at the seventh postoperative day:the FPP was (30 ± 5) cmH2 O,(29 ± 5) cmH2 O,(29 ± 5) cmH2 O,(29 ± 5) cmH2 O,(28 ± 5) cmH2 O,(28± 5) cmH2 O,(28 ± 5) cmH2 O,(29 ± 5) cmH2 O,(29 ± 5) cmH2 O,(30 ± 5) cmH2 O,(30± 5)cmH2O,(30±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(32±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(31±5)cmH2O,(30± 5) cmH2O,(30±5) cmH2O from 00:00 to 24:00 at the seventh day postoperatively.Level of FPP was higher from 12:00 to 21:00 and lower from 01:00 to 08:00,with a peak value at 17:00 and valley value from 04:00 to 06:00.(3) Comparison of FPP before and after Valsalva maneuvre:the FPP was (30± 5) cmH2O and (32± 5) cmH20 before and after Valsalva manoeuvre,respectively,showing a statistically significant difference (t =82.72,P＜ 0.05).(4) Relationship of FPP with mean arterial pressure and heart rate.Linear correlation analysis showed positive correlations of FPP with mean arterial pressure and heart rate respectively,but the correlation was not significant (r =0.10,0.16,P＜ 0.05).Conclusions FPP can be reduced significantly after splenectomy combined with pericardial devascularization intraoperatively and it rises briefly again after operation.FPP has regularly circadian fluctuations and is significantly increased by Valsalva Manoeuvre.There is a positive correlation of FPP with mean arterial pressure and heart rate respectively,but the correlation is not significant.

Objective: To observe the effect of bisoprolol on cardiac function in heart failure (HF) rats and to explore the mechanism. Methods: The experimental rats were divided into 6 groups: Control group, with normal healthy rats, Sham group, the rats received intraperitoneal injection of normal saline; chronic heart failure (CHF) model was successfully established in 40 rats and divided into 4 groups: CHF group, CHF+bisoprolol (Bis) group, CHF+captopril (Cap) group and CHF+Bis and Cap group.n=10 in each group. The cardiac function was observed among different groups; plasma BNP level was measured by ELISA, myocardial miR-25-3p expression was examined by RT-PCR, protein expressions of SERCA2a and phospholamban (PLB) were detected by Western blot analysis and SERCA2a activity was determined by inorganic phosphorus method. Results: Compared with Control group, CHF group showed decreased cardiac output (CO), left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), reduced expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while increased plasma BNP and miR-25-3p expression, allP<0.01. Compared with CHF group, CHF+Bis, CHF+Cap and CHF+Bis and Cap groups had increased CO, LVFS, LVEF, elevated expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while decreased plasma BNP and miR-25-3p expression, allP<0.05.Conclusion: Bisoprolol could improve cardiac function in HF rats, which might be related to down regulating myocardial miR-25-3p expression, up regulating myocardial protein expressions of SERCA2a, PLB and enhancing SERCA2a activity.

Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart fail-ure.Methods Male SD rats were randomly divided into normal control group (control group), sham operation group ( sham group ) , model group , bisoprolol group ( Bis group ) , captopril group ( Cap group ) and bisoprolol plus captopril group[(Bis+Cap)group], heart failure rat model was induced by intraperitoneal injections of doxorubicin .Distilled water, bisoprolol, captopril or bisoprolol plus captopril were administrated by gastrogavage for 35 days, respectively. Indices of cardiac function and plasma levels of B-type natriuretic peptide ( BNP) were measured , myocardial expres-sion of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban (PLB) were detected by Western blot , myocardial SERCA2a activity was determined by the inorganic phosphorus method . Results Cardiac function in model group decreased significantly while plasma levels of BNP were significantly higher than those of control group ( P<0.01 ) .Myocardial expression of miR-25-3p in model group was significantly higher while myocardial levels of SERCA 2a and PLB,SERCA2a activity were significantly lower than those of con-trol group(P<0.01).Cardiac function in Bis group , Cap group and Bis +Cap group improved significantly while plasma levels of BNP were significantly lower than those of model group ( P<0.01 ) .Myocardial expression of miR-25-3p in Bis group, Cap group and Bis +Cap group were significantly lower while myocardial levels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Bis group and Bis +Cap group were significantly higher than those of model group ( P<0.05 ) .Conclu-sions Bisoprolol therapy improves cardiac function in rats with heart failure , which may be related to inhibition of myocardial miR-25-3p, increasing myocardial SERCA2a and PLB levels, enhancing SERCA2a activity.

Objective To observe the effects of therapy of supplementing spleen to strengthen lung on patients with adenomatous colonic polyps (ACP) after endoscopic removal . Methods One hundred ACP patients with spleen deficiency and dampness blended with blood stasis were randomly divided into 2 groups after endoscopic removal, 50 cases in the treatment group and 50 cases in the control group. Both groups were treated with diet and behavioral therapy, and the treatment group was simultaneously given oral use of modified Shen Ling Baizhu Powder plus self-moxibustion of bilateral acupoint Zusanli point. After treatment for 6 months and 1.5 years, all of the patients were asked to do the examination of colonoscopy, body mass, body mass index (BMI), and triglyceride (TG). Results (1) After treatment, the mean overall symptom scores of the two groups were improved (P < 0.01 compared with those before treatment) , and the improvement of the treatment group was superior to that of the control group(P < 0.01).(2) After treatment for 6 months and 1.5 years, the recurrence rate of ACP in the treatment group was lower than that in the control group(P < 0.05).(3) After treatment for 6 months and 1.5 years, the body mass, BMI and TG of the treatment group were significantly different from those before treatment(P<0.05), while the control group showed no significant changes(P > 0.05). The effect of the treatment group on improving body mass, BMI and TG was better than that of the control group (P < 0.05). Conclusion The therapy of supplementing spleen to strengthen lung is effective on relieving symptoms of ACP patients, and also has an effect on decreasing BMI and TG as well as the recurrence of ACP after endoscopic removal.

Objective To investigate the effects of p300/CBP on histone acetylation of Foxp3 gene and its roles in the immunological pathogenesis of Kawasaki disease (KD).Methods Forty-six children with KD and twenty-eight age-matched health children were consented to participate in this study.Co-immunoprecipitation and real-time PCR were performed to detect Foxp3-associated acetylation levels of histone H4 and binding abilities of p300, CBP, pSmad3 (phosphorylated mothers against decapentaplegic homolog 3) and NF-AT (nuclear factor of activated T cells) with Foxp3 gene in CD4+ T cells.The percentages of CD4+CD25high Foxp3+ cells (Treg) and the expression of Foxp3, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), p300, CBP, TGF-βRⅡ (transforming growth factor β receptor Ⅱ) and pLAT1 at protein level were analyzed by flow cytometry.Quantitative real-time PCR was used to measure the expression of Foxp3, IL-10, TGF-β, TGF-βRⅠ, Egr-1 (early growth response protein 1), RARα (retinoic acid receptor α) and PLCγ1 (phospholipase C-γ1) in Treg cells at mRNA level.Plasma concentrations of TGF-β and retinol acid (RA) were measured by enzyme-linked immunosorbent assay.Results (1) The percentages of Treg cells, levels of Foxp3 and molecules associated with suppressive function of Treg cells (TGF-β, IL-10 and CTLA4), acetylation levels of histone H4 associated with promoter, conserved non-coding DNA sequence 1 (CNS1) and CNS2 of Foxp3 gene decreased remarkably during acute KD (P<0.05), but were restored after IVIG therapy (P<0.05).Meanwhile, all of the aforementioned items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) (P<0.05).No significant differences in histone H4 acetylation associated with CNS3 were found among different groups (P>0.05).(2) The levels of p300 and CBP in Treg cells and their binding abilities with Foxp3 gene were down-regulated significantly during acute KD (P<0.05), but were restored to some extent after IVIG treatment (P<0.05).The Foxp3-associated histone acetylation was positively correlated with the expression of p300 and CBP at mRNA level during acute KD (r=0.65, 0.42, P<0.05).Furthermore, the expression of p300 and CBP and their binding abilities with Foxp3 gene in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(3) Compared with healthy subjects, plasma concentrations of TGF-β and RA and the expression of TGF-βRⅠ/Ⅱ/Egr-1, RARα and pLAT1/PLCγ1 were down-regulated during acute KD (P<0.05);the binding abilities of pSmad3 and NFAT with Foxp3 gene were reduced remarkably in patients with acute KD (P<0.05).All the items mentioned above were restored after IVIG treatment (P<0.05).Moreover, the ten items aforementioned in KD-CAL+ group were lower than those in KD-CAL-group (P<0.05).(4) Higher acetylation levels of histone H4 associated with promoter, CNS1 and CNS2, and enhanced binding abilities of p300 and CBP with Foxp3 gene were found in CD4+ T cells isolated from patients with acute KD after co-stimulation with TGF-β, RA and anti-CD3/CD28 antibodies as compared with those in CD4+ T cells without stimulation (P<0.05).However, no statistical difference in the acetylation level of histone H4 associated with CNS3 was found between the two groups (P>0.05).Conclusion Hypoacetylation of histone H4 associated with Foxp3 gene caused by insufficient expression of p300/CBP and their impaired binding abilities might be involved with immune dysfunction in KD.IVIG therapy regulates the expression of p300/CBP and their binding abilities with Foxp3 gene through up-regulating TGF-β signal.

Objective To investigate the effects of SMYD3 and MLL5 on histone methylation of Transcription factor forkhead box protein 3 (Foxp3) gene and its roles in the immunological pathogenesis of Kawasaki disease (KD). Methods Forty-two children with KD and 26 age-matched healthy children were consented to participate in this study. Co-Immunoprec-ipitation and real-time polymerase chain reaction (PCR) was performed to determine Foxp3-associated histone methylation levels of H3K4me3 and H3K27me3, and binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells. The proportion of CD4+CD25high Foxp3+cells (Treg) and protein levels of Foxp3, cytotoxic T lymphocyte associated antigen-4 (CTLA4), TGF-βRⅡand pSmad3 were analyzed by flow cytometry. Quantitative real-time PCR was used to evaluate levels of Foxp3, interleukin (IL)-10, GITR, TGF-βRⅠand RARαmRNA in CD4+T cells. Plasma concentrations of TGF-βand retinol acid (RA) were measured by enzyme-linked Immunosorbent assay. Independent-samples t-test was used as the statistical method in this study. Results ① The proportion of Treg, expression levels of Foxp3 and molecules associated with suppressive function of Treg cells(IL-10, GITR and CTLA4), and histone methylation levels of H3K4me3 associating with promoter, conserved non-coding DNA sequence (CNS) 1 and CNS2 of Foxp3 gene decreased remarkably during acute KD [Promoter:(5.4±1.8)%vs (9.1±2.2)%;CNS1:(2.6±0.9)% vs (3.8±1.1)%; CNS2: (2.4±0.8)% vs (4.2±1.0)%; t=5.50, 6.02, 9.56, 7.92, 7.97, 4.76, 7.73, 5.01, 8.66; P<0.05], and restored after intravenous immunoglobulins (IVIG) therapy [Promoter: (7.2 ±2.1)% vs (5.4 ±1.8)%; CNS1:(3.6±1.4)% vs (2.6±0.9)%; CNS2: (3.6±1.4)% vs (2.4±0.8)%; t=5.56, 4.59, 7.01, 6.04, 5.89, 4.83, 4.45, 4.00, 5.12; P<0.05]. Meanwhile, the nine former items in KD patients with coronary artery lesions (KD-CAL+) were lower than those without coronary artery lesions (KD-CAL-) [Promoter: (4.11±1.45)% vs (6.16±1.93)%; CNS1:(1.99±0.87)%vs (2.96±1.10)%;CNS2: (1.75±0.63)%vs (2.72±1.16)%;t=6.28, 3.24, 4.56, 3.69, 3.38, 4.40, 3.65, 3.00, 3.51; P<0.05]. No significant difference of H3K4me3 associated with CNS3 and H3K27me3 were found among the groups (t=1.03, 0.91, 1.48 and 0.79, 0.82, 1.53; P>0.05). ② Binding levels of SMYD3 and MLL5 with Foxp3 gene in CD4+T cells were down-regulated significantly during acute KD (t=6.63, 6.15; P<0.05), and restored to some extent after IVIG treatment (t=5.36, 4.56; P<0.05). Positive correlations between binding levels of SMYD3 and MLL5 and expression level of Foxp3 mRNA were detected in patients with acute KD (r=0.62、0.45, P<0.05). Furthermore, Binding levels of SMYD3 and MLL5 with Foxp3 gene in KD-CAL+group were lower than those in KD-CAL- group (t=4.11, 4.31; P<0.05). ③ Compared with healthy controls, plasma concentration of TGF-β and RA, and expressions of TGF-βRⅡ, TGF-βRⅠ, pSmad3 and RARα were down-regulated during acute KD (t=11.54, 12.81, 7.43, 16.10, 8.25, 12.06; P<0.05), and elevated remarkably after IVIG treatment (t=8.40, 6.24, 5.94, 11.78, 6.27, 8.30; P<0.05). Simultaneously, all the items aforementioned in KD-CAL+ group were found to be lower than those in KD-CAL-group (t=3.58, 3.30, 3.82, 5.27, 4.71, 3.78; P<0.05). Conclusion Hypomethylation of H3K4me3 associated with Foxp3 gene caused by insufficient binding levels of SMYD3/MLL5 may be involved with immune dysfunction in Kawasaki disease.

ABSTRACT:Objective To investigate the effects of Xiefei Lishui recipe on left ventricle remodeling in rats with heart failure.Methods Heart failure rat model was induced by intraperitoneal injections of doxorubicin. Rats were randomly divided into sham operation group (sham group),model group,traditional Chinese medicine group (TCM group),captopril group,and digoxin group.Distilled water,TCM [22 g/(kg · d)],captopril [19 mg/(kg·d)],and digoxin [32μg/(kg·d)]were administered by gastrogavage in rats in different groups for 35 days,respectively.Indices of ventricle remodeling and cardiac function,plasma levels of B-type natriuretic peptide (BNP),rennin (REN),angiotensin Ⅱ(AngⅡ)and aldosterone (ALD)were measured.Cardiomyocyte apoptosis index and collagen volume fraction (CVF)were analyzed.We also assayed myocardial mRNA expressions of MMP-2/9 and TIMP-1/2,and their tissue inhibiting factors TIMP-1 and TIMP-2.Results Compared with those in sham group,in model group cardiac function was significantly decreased,which could be significantly increased by TCM or captopril or digoxin,indices of cardiac remodeling were significantly increased,which could be significantly decreased by TCM or captopril (P<0.01 or P<0.05).Plasma levels of BNP,REN,AngⅡ and ALD,cardiomyocyte apoptosis index and CVF in model group were significantly increased,could be significantly decreased by TCM or captopril (P<0.01 or P<0.05).Myocardial mRNA expressions of MMP-2,MMP-9,TIMP-1 and TIMP-2 in model group were significantly upregulated compared with those in sham group, which could be significantly downregulated by TCM (P<0.01 or P<0.05).Conclusion Xiefei Lishui recipe can attenuate left ventricle remodeling and improve cardiac function in rats with heart failure, which may be related to downregulating myocardial mRNA expressions of MMP-2 ,MMP-9 ,TIMP-1 and TIMP-2 in the left ventricle as well as inhibiting cardiomyocyte apoptosis and myocardial fibrosis.