Objective We aimed to evaluate the clinical efficacy of promoting blood circulation and eliminating phlegm method in preventing and treating patients with hydrocephalus after acute intracerebral hemorrhage.Methods This study included 139 patients with acute intracerebral hemorrhage who visited Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Guangyuan Hospital of Traditional Chinese Medicine,Affiliated Hospital of North Sichuan Medical College,Meishan Hospital of Traditional Chinese Medicine,and Xuyong Hospital of Traditional Chinese Medicine from September 2019 to June 2023.Patients who met the exposure factors of"using the method of promoting blood circulation and eliminating phlegm"were classified into the integrated Chinese and Western medicine cohort,while those who did not meet the exposure factors were classified into the Western medicine cohort.Clinical efficacy,incidence of hydrocephalus after intracerebral hemorrhage,sum of maximum distance between the anterior horn of the lateral ventricle and the head of the caudate nucleus(Huckman value),size of the hematoma,incidence of endpoint events,National Institutes of Health Stroke Scale(NIHSS)score,Modified Rankin Scale(mRS)score,and Barthel index score between two cohorts were compared.Results Total clinical effective rates for patients with hydrocephalus in the two cohorts were 60.0%and 75.0%,respectively.The total effective rate of the integrated Chinese and Western medicine cohort was higher than that of the Western medicine cohort(P<0.05).After 28 days of treatment,the incidence of hydrocephalus in patients in the integrated Chinese and Western medicine cohort was lower than that of the Western medicine cohort,and the Huckman value decreased compared with the Western medicine cohort(P<0.05).Compared with 24 hours after onset,both cohorts showed a reduction in hematoma size after 28 days of treatment;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort had reduced hematoma size(P<0.05).After 6 months of onset,the number of deaths in the integrated Chinese and Western medicine cohort decreased compared with the Western medicine cohort(P<0.05).Compared with 28 days of treatment,the NIHSS and mRS scores of the patients in both cohorts decreased after 6 months,while the Barthel index score increased;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort showed a decrease in the NIHSS and mRS scores after both 28 days of treatment and 6 months,while the Barthel index score increased(P<0.05).Conclusion Promoting blood circulation and eliminating phlegm can effectively prevent and treat hydrocephalus after intracerebral hemorrhage and does not increase the risk of bleeding within 24 hours.

Objective To establish a mouse model of liver aging induced by irradiation combined with hepatectomy.Methods A model was established via single irradiation combined with hepatectomy.The survival rate,body weight,liver index and liver function of the mice were detected.The expressions of senescence-associated secretory phenotype factors in serum were detected with enzyme-linked immunosorbent assay(ELISA)and flow cytometry.The mRNA levels of senescence-associated secretory phenotype factors and telomerase in liver tissue were detected by real-time quantitative PCR(qPCR).The expressions of cyclin dependent kinase inhibitor 1A(CDKN1A)and cyclin dependent kinase inhibitor 2A(CDKN2A)were determined by Western blotting.ELISA was used to calculate senescence-associated β-galactosidase(SA-β-Gal)and lipofuscin levels.Tissue malondialdehyde levels were measured using the thiobarbituric acid(TBA)method.The size of hepatocyte nuclei and lipid accumulation were detected by hematoxylin-eosin(HE)stainingand oil-red-O while triglyceride levels in the liver were studied with the weighing method.Results After irradiation combined with hepatectomy,the body weight of mice was significantly reduced,the liver index was not significantly affected,but the transaminase level was significantly increased.The levels of SA-β-Gal and lipofuscin increased while telomerase activity decreased significantly,and the nucleus size increased.The expressions of cyclin dependent protein kinase inhibitors CDKN1A and CDKN2A increased.The levels of senescence-associated secretory phenotype factors were significantly increased.Hepatic lipid deposition and oxidative damage were aggravated.Conclusion A mouse model of liver aging induced by irradiation combined with hepatectomy has been established.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

OBJECTIVES: This work aimed to investigate the molecular mechanism of cyclic tensile stress (CTS) stimulating autophagy in human periodontal ligament cells (hPDLCs). METHODS: hPDLCs were isolated and cultured from normal periodontal tissues. hPDLCs were loaded with tensile stress by force four-point bending extender to simulate the autophagy of hPDLCs induced by orthodontic force du-ring orthodontic tooth movement. XMU-MP-1 was used to inhibit the Hippo signaling pathway to explore the role of the Hippo-YAP signaling pathway in activating hPDLC autophagy by tensile stress. The expression levels of autophagy-related genes (Beclin-1, LC3, and p62) in hPDLCs were detected by real-time quantitative polymerase chain reaction. Western blot was used to detect the expression levels of autophagy-related proteins (Beclin-1, LC3-Ⅱ/LC3-Ⅰ, and p62) and Hippo-YAP pathway proteins (active-YAP and p-YAP) in hPDLCs. Immunofluorescence was used to locate autophagy-related proteins (LC3-Ⅱand p62) and Hippo-YAP pathway proteins (active-YAP) of hPDLCs. RESULTS: CTS-activated autophagy in hPDLCs and expression of autophagy-related proteins initially increased and then decreased; it began to increase at 30 min, peaked at 3 h, and decreased (P<0.05). CTS increased the expression of active-YAP protein and decreased the expression of p-YAP protein (P<0.05). When XMU-MP-1 inhibited the Hippo-YAP signaling pathway (P<0.05), active-YAP protein was promoted to enter the nucleus and autophagy expression was enhanced (P<0.05). CONCLUSIONS The Hippo-YAP signaling pathway is involved in the regulation of autophagy activation in hPDLCs under CTS.
Humans ; Hippo Signaling Pathway ; Periodontal Ligament/metabolism* ; Beclin-1/metabolism* ; Cells, Cultured ; Autophagy

Objective To investigate the correlation between mammographic features in BIGRADS 3,4 and the corresponding histological findings.Methods 442 patients with 46 9 lesions categorized as 3 ,4 in BIGRADS on mammography from July 20 1 3 to February 20 1 5 were retrospectively analyzed.The correlation between mammographic features and histological findings was statistically analyzed.Results Among the 469 lesions,130 lesions were categorized as BIGRADS 3,with 13 pathologically confirmed malignant lesions and 117 benign lesions.There were 3 3 9 lesions in BIGRADS 4,with 9 8 malignant lesions and 241 benign lesions.There were statistical differences between benign and malignant lesions (P＜0.05)in mass morphology,mass margin,calcification morphology,calcification distribution,architectural distortion,asymmetries and axillary adenopthy.There were no statistically significant differences (P＞0.05 )in breast composition, mass density or location.The logistic regression analysis with above mentioned significance indexs showed that the F value was 4.3 1 1 , with the significance probability (P＜0.001 ).The mass shape,the edge of the mass,the calcification shape,the calcification distribution,the structure distortion,the asymmetrical compact shadow,and the axillary lymph node enlargement were all correlated with the benign and malignant of the tumors.Conclusion The mammographic features of BIGRADS category 3 and 4 including the mass morphology, margin,calcification morphology,calcification distrubution,architectural distortion,asymmetries,and axillary adenopthy could help us to improve the accuracy diagnoses between benign and malignant lesions.

Objective To explore the molecular pathological mechanism of gout, and to explore the mechanism of how interleukin (IL)-37 influencing PDZK1 protein in gout through nuclear factor κB (NF-κB) pathway. Methods HK-2 cells were stimulated with inflammatory signal IL-37. The expression of PDZK1 and its subcellular localization were detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR) at different concentrations of IL-37 (defined as group A), PDTC+IL-37 (defined as group B), Wortmannin+IL-37 (defined as group C), respectively.The changes of PDZK1 protein expression in HK-2 cells were detected by adding inhibitor PDTC (NF-κB pathway inhibitor) or Wortmannin (PI3K pathway inhibitor) and inflammatory signal stimulating protein imprinting method. The comparative t test was used for statistical analysis between groups A, B and A and C. Results The average levels of PDZK1 mRNA were as follows:(group A: 28.71 ±0.35, 28.57 ±0.31, 28.78 ±0.28, 28.63 ±0.29, 28.62 ±0.19; group B: 28.71 ±0.31, 28.83 ±0.27, 28.58±0.26, 28.73±0.36, 28.68±0.35;group C:28.81±0.32, 28.91±0.29, 28.72±0.24, 28.59±0.18, 28.58±0.22). There was no significant change in PDZK1 mRNA level in group A and B. The same IL-37 was found in group A and B. The values of T were 5.73, 4.72, 4.69, 5.86 and 6.79, respectively. The P values were all greater than 0.05, and there was no significant difference between the two groups. The values of T were 6.78, 7.13, 7.47, 6.38 and 5.98 in the same IL-37 concentration groups of A and C, respectively, and the P values were all greater than 0.05, with no significant difference. The levels of PDZK1 protein in the three groups by Western blot analysis were as follows: (group A: 0.200±0.082, 0.412±0.032, 0.723±0.063, 1.202±0.021, 1.222±0.023;group B: 0.124±0.064, 0.303±0.081, 0.325±0.062, 0.223±0.071, 0.343±0.052; group C: 0.017±0.022, 0.204± 0.015, 0.187±0.053, 0.302±0.051, 0.404±0.051), The levels of PDZK1 protein in group A treated with different concentrations of IL-37 followed by the concentration of IL-37. The level of PDZK1 protein in group B increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group B was lower than that in the group treated with IL-37 only, and decreased when the concentration of IL-37 was 40 ng/ml.The level of PDZK1 protein in group C increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group C was lower than that in the group treated with IL-37 only, and the same concentration of IL-37 in group A and B. The values of T were 1.83, 1.37, 1.64, 1.57 ,1.49, with P values greater than 0.05. There was no significant difference between the two groups. The values of T were 1.28, 1.37, 1.26, 1.42, 1.39 in the same concentration of IL-37 in group A and C, with P values greater than 0.05, with no significant difference.The results of immunofluorescence analysis showed that the trend of the three groups was basically consistent with that of Western-Blot. Conclusion The pathogenesis of gout induced by IL-37 through PDZK1 protein may not occur at the transcriptional level, but may occur at the level of protein translation.

OBJECTIVETo investigate the efficacy of combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication for cardiochalasia patients.

METHODSClinical data of 11 cardiochalasia patients who underwent combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication by the same medical team from January 2015 to December 2016 at The Second Hospital of Jilin University were retrospectively analyzed. The procedure was as follows: an incision was made in the anterior wall of esophagus and dissection of esophageal muscular layer was performed, then the bulged esophageal mucosa was covered by the fundus after 180 degrees fold to the right (fundoplication), finally the gastric fundus was joined to the right diaphragmatic foot by 3 to 5 knotted suture. The efficacy was judged by the Eckardt scoring standard: the postoperative Eckardt score ≤3 points indicated effectiveness, otherwise the treatment was invalid.

RESULTSCombined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication was completed successfully in all the 11 patients without any subsequent laparotomy and death. The mean operative time was 85 (78 to 137) min, blood loss was 15 (5 to 35) ml, and no upper digestive tract perforation occurred. The mean postoperative hospital stay was 7.0(6 to 9) d. After the operation, the pressure of lower esophageal sphincter decreased significantly compared to that before operation [(5.31±6.23) mmHg vs. (35.72±17.13) mmHg, P<0.05], and the Eckardt score decreased significantly as well (0.53±0.56 vs. 6.17±1.17, P<0.05). During the follow-up of 2 to 23 months, there was no postoperative mortality. One case experienced mild gastroesophageal reflux 6 months after operation, and another patient had recurrent dysphagia 17 months after operation, who both were improved after receiving proton pump inhibitors or gastric dynamic drugs, and balloon dilation.

CONCLUSIONCombined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication is an effective and safe surgical procedure for cardiochalasia with minimal invasion and fast recovery.

Aim To investigate the protective mechanism of anisodine hydrobromide against cerebral ischemia-reperfusion injury in rats.Methods In vivo: the cerebral ischemia-reperfusion injury model was established by middle cerebral artery occlusion(MCAO)via suture method in rats;the rats were injected anisodine hydrobromide(1.2,0.6,0.3,0.15 mg·kg-1);the morphological changes were detected by HE staining;the Nissl staining was used to count the number of surviving neurons;the activity of CAT and LDH,the LPO contents in the brain tissue were measured;the expressions of Bax,Bcl-2,caspase-3 and p-Akt in brain tissue were detected by Western blot.In vitro: Western blot assay was used to determine the expression of Bax,Bcl-2,caspase-3 and p-Akt protein expression in the OGD-R model of PC12 cells.The signal pathway of anisodine hydrobromide was identified.Results Anisodine hydrobromide with the dose of 0.15 mg·kg-1 could significantly lessen the morphological changes,and improve the number of surviving neurons;the dose of 0.3 and 0.15 mg·kg-1 could significantly improve the activity of CAT;the dose of 0.3 mg·kg-1 could significantly reduce the contents of LPO in the rat brain tissue;the dose of 1.2 mg·kg-1 could significantly decrease the activity of LDH;the dose of 0.15～1.2 mg·kg-1 could inhibit the expression of Bax,promote the expression of p-Akt in rat brain tissue.All the doses except 0.15 mg·kg-1 could promote the expression of Bcl-2 in rat brain tissue.In vitro,the results showed that anisodine hydrobromide in 25～100 μmol·L-1 could significantly improve the expression of Bcl-2 and the ratio of Bcl-2/Bax,and the dose of 50 μmol·L-1 could significantly improve the ratio of p-Akt/Akt.Conclusion The mechanism of anisodine hydrobromide against cerebral ischemia-reperfusion injury model rats might be related to its anti-oxidative activity and the activation of Akt.

OBJECTIVE:To study the effects of anisodine hydrobromide on cell apoptosis and extracellular signal-regulated pro-tein kinase 1/2 (ERK1/2) phosphorylation (p-ERK1/2) level in brain tissue of model rats with acute cerebral ischemia-reperfusion injury. METHODS:Rats were randomly divided into sham operation group,model group,positive control group(nimodipine 1.0 mg/kg),anisodine hydrobromide high-dose,medium-dose,low-dose,extreme low-dose groups(1.2,0.6,0.3,0.15 mg/kg),8 in each group. Suture method was used to establish the rat models with acute cerebral ischemia-reperfusion injury. Rats were intrave-nously injected once in tail at 2nd of ischemia and 6th of reperfusion. Then adenosine triphosphate (ATP) enzyme activity,Ca2+content,cell apoptosis in brain tissue,p-ERK1/2 protein expression in brain tissue,and p-ERK1/2/total ERK1/2 (t-ERK1/2) pro-portion in brain tissue of rats were detected after 22 h of reperfusion. RESULTS:Compared with sham operation group,ATP en-zyme activity in brain tissue of rats in model group was obviously decreased,Ca2+ content was obviously increased,density of cell apoptosis in brain tissue was obviously increased,with statistical significances(P<0.01). Compared with model group,density of cell apoptosis in brain tissue was obviously decreased in each administration group;Ca2+ contents in brain tissue of rats in positive control group,anisodine hydrobromide high-dose,low-dose groups were obviously decreased;and p-ERK1/2/t-ERK1/2 proportion in brain tissue of rats in anisodine hydrobromide high-dose,low-dose,extreme low-dose groups were obviously increased,with sta-tistical significances(P<0.05 or P<0.01);the other differences were not statistically significant(P>0.05). CONCLUSIONS:An-isodine hydrobromide can inhibit the cell apoptosis in brain tissue of model rats with acute cerebral ischemia-reperfusion injury,andthe mechanism may be related with activating ERK1/2 signal pathway and regulating ATP enzyme activity to decrease the Ca2+content in the brain tissue.