Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.

Background: Post - stroke constipation is a commonly seen complication, which can reduce the quality of life of patients. Therefore, it is particularly important to explore the treatment of post-stroke constipation. Aims: To explore the effect of gastrointestinal rehabilitation (visceral fascial manipulation plus middle - frequency electrical stimulation) on quality of life, substance P (SP) and 5-hydroxytryptamine (5-HT) in constipation patients after stroke. Methods: Seventy constipation patients after stroke from Oct. 2020 to Oct. 2011 at Shanghai Tongren Hospital were enrolled and randomly divided into control group (lactulose treatment) and treatment group (gastrointestinal rehabilitation treatment). Montreal cognitive assessment (MoCA), Barthel index (BI), self-rating anxiety/depression scale (SAS/SDS), gastrointestinal symptom rating scale (GSRS), Wexner constipation scale, and patient assessment of constipation-quality of life (PAC-QOL) were performed before and after treatment. Serum SP, 5 - HT were determined by ELISA. Results: After the treatment, no significant difference in MoCA score was found in both two groups, and SAS score, SDS score, GSRS score, Wexner score and PAC-QOL score were significantly decreased (P<0.05). Repeated measures ANOVA showed that significant differences in SAS score, SDS score were found between the two groups (P<0.05), and the decreases of SAS score and SDS score were more obvious in treatment group. No significant differences in MoCA score, BI score, GSRS score, Wexner score and PAC- QOL score were found between the two groups (P>0.05). Serum SP, 5-HT levels in treatment group were significantly higher than those in control group (P<0.05). Conclusions: In the treatment of constipation after stroke, the gastrointestinal rehabilitation therapy of‘visceral fascial manipulation plus middle-frequency electrical stimulation’has the therapeutic effects equivalent to drug therapy, and is worthy for promoting in clinical treatment.

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.

Objective: To understand the epidemiological feature and prevalent trend of pneumoconiosis in Ankang City, pertinently put forward the prevention and control strategy, and provide the basis for comprehensive prevention and treatment of pneumoconiosis. Methods: China Information System for Disease Control and Prevention has exported the network report data of "occupational diseases and occupational health information monitoring" from January 1, 2006 to December 312017 and has created the database; has investigated and supplemented the occupational disease reporting results from January 1, 1974 to December 31, 2005; has conducted the data cleansing through SPSS17.00; has conducted the statistical description and analysis according to pneumoconiosis diagnosis time, age, sex, length of service, industry, and etc. Results: From 1974 to 2017, Ankang City has accumulatively reported 1047 cases of various occupational pneumoconiosis; of which, 992 new cases and 55 stage development cases. Entities of pneumoconiosis include silicosis, coal workers pneumoconiosis, electric arc welders pneumoconiosis, cement pneumoconiosis and asbestosis; number of new cases of silicosis ranks first, the second is coal workers pneumoconiosis. Average length of employment of the occurrence of pneumoconiosis is (15.01±8.95) years; average length of age of the occurrence is (47.11±7.86) years. Distribution of pneumoconiosis involves 8 industries; the first is mining industry (54.23%) , the second is construction industry (27.52%) , and the third is public management, social security and social organization (12.70%) . Pneumoconiosis involves 24 types of work; the first is drillman (47.28%) , the second is main coal miners (15.52%) , and the third is blasters (13.31%) . Conclusion Prevention and treatment of pneumoconiosis in Ankang City gives priority to silicosis and coal workers pneumoconiosis, puts emphasis on strengthening the prevention of pneumoconiosis of drillman in the mining industry; the occurrence of pneumoconiosis is in a linear upward trend from 2012.

Objective To study the protective effects of human umbilical cord-derived mesenchymal stem cells (ucMSCs)against severe acute pancreatitis (SAP) in rats.Methods A total of 135 Sprague-Dawley male rats were randomly divided into Sham group,SAP group and SAP+ucMSCs group (45 each).SAP+ucMSCs group:Severe acute pancreatitis was induced by injecting 5％ sodium taurocholate (0.1ml/100g) into the common bilio-pancreatic duct and then CM-DiI-labeled ucMSCs at 1 × 107cells/kg were injected via the tail vein.All the rats were sacrificed 12,24 and 72 hours after SAP.The 72h death rate was counted.Pathological changes in the pancrease were detected by HE staining and pathological score was graded,ucMSCs colonization was observed by fluorescence microscopy.The serum levels of amylase,lipase,TNF-α,IL-1β,IL-4 and IL-10 were determined by ELISA.Results ucMSCs colonize the injured area of pancreatic tissue,the 72h death rate was reduced,and the serum amylase and lipase were also reduced significantly.Moreover,ucMSCs significantly reduced the pathological score of the pancrea and the level of proinflammatory cytokines (TNF-α and IL-1β),but the levels of anti-inflammatory cytokines were increased (IL-4 and IL-10).Conclusion Transplantation of ucMSCs can reduce the severity of pancreatic injury and inflammation in SAP rats.

Objective To observe the effects of large-dose ambroxol hydrochloride on lung ischemia-reperfusion injury (LIRI)and discuss the protection of ambroxol hydrochloride on Toll-like receptor 4 (TLR4)/nuclear transcription factor-kappa B (NF-κB ) after lung ischemia-reperfusion injury in rats.Methods We randomly assigned 60 healthy SD rats into four groups (n=15 for each):control group,ambroxol hydrochloride group (0.75 g/L),ischemia-reperfusion group (I/R),and I/R+ambroxol hydrochloride group.The ambroxol hydrochloride group and I/R+ambroxol hydrochloride group were injected large dose of ambroxol hydrochloride by intravenous injection.The control group and the I/R group received normal saline.The effects of ambroxol hydrochloride on lung ischemia-reperfusion (LIR)-induced pathological changes and inflammatory cytokines release level were examined.DNA ends situ labeling assay (TUNEL)was used to detect the apoptosis of cells.NF-κBp6 5 was detected by immunohistochemistry.In addition,the TLR4 signaling pathway activation in lung tissues was detected by Western blot analysis.Results Compared with those in the control group,some hemorrhage and inflammation changes of lung tissues were observed;the W/D ratio,inflammatory cytokines,apoptosis of cells,NF-κBp6 5 and TLR4 signaling pathway protein expression in I/R group was obviously increased.Compared with I/R group,some mild hemorrhage and inflammation changes of lung tissues were observed;W/D ratio,inflammatory cytokines,apoptosis of cells, NF-κBp6 5 activity, and TLR4 signaling pathway expression were all decreased significantly in I/R+ambroxol hydrochloride group.Conclusion Large dose of ambroxol hydrochloride can protect rats with lung ischemia-reperfusion injury by downregulating TLR4 signaling pathway.

Objective To evaluate the role of autophagy on acute kidney injury after liver transplantation.Method Fifty-six healthy male Sprague-Dawley rats were randomly assigned into 4 groups:sham group,orthotopic liver transplantation (OLT) group,sirolimus pretreated (SRL) group and 3-methyladenine pretreated(3-MA) group.OLT model was established.Then the rats were sacrificed at 6 h after reperfusion.The renal function and the extent of oxidative stress relative proteins malondialdehyde (MDA) and superoxide dismutase (SOD) were observed.The levels of apoptosis relative genes caspase-3 and cyt c and the expression of autophagy relative proteins were detected.The pathological changes were microscopically examined in renal tissues.TUNEL staining was used to observe the apoptosis of tubular epithelial cells.Transmission electron microscopy was applied to observe the ultrastructure changes of tubular epithelial cells.Result As compared with sham group,OLT and 3-MA groups showed a serious renal injury including cellular vacuolization,loss of brush borders,and a significant rise in BUN,Cr and MDA,while a decrease in SOD activity.The levels of caspase-3 mRNA and cyt c rnRNA were increased significantly.Whereas compared to OLT and 3-MA groups,renal function and oxidative stress levels in SRL group ameliorated,and histopathologic damage and apoptosis alleviated after OLT.Simultaneously,the levels of caspase-3 mRNA and cyt c mRNA were decreased.The expression of beclin-1 and LC3-]Ⅱ was effectively upregulated.Conclusion Autophagy could alleviate acute kidney injury after liver transplantation through inhibiting oxidative stress and apoptosis.

Objective To investigate the expression and the role of Tim-3 and Th-17 in ITP patients and to research their clinical application. Methods Total 42 active ITP patients and 39 healthy donors were recruited in this research. The expressions of Th17 and CD4+ CD25+ Treg were measured with flow cytometer. IL-17, IFN-γ levels as well as IL-4 plasma levels were determined by ELISA. The mRNA expression of Tim-3, IFN-γ, IL-4 and T-bet were measured using RT-PCR in all samples. Results The expression of Th17 cells in ITP patients was (2.41 ± 1.43 )%, which was significantly higher than control group ( 1.08 ± 0.59)% ( t = 5.35, P < 0.05 ). But the percentage of Treg in ITP patients was ( 1.64 ±0.74)%, which was lower than control group (3.12 ±0.52)% (t = 10.33, P <0.05). The levels of IL-17 in plasma of ITP and controls were ( 14.42 ±6.37) ng/L and ( 13.91 ±4.47) ng/L respectively (t =0.42, P > 0.05). The level of IFN-γin plasma of ITP was (55.74 ± 15.25 ) ng/L, which was higher than control group (31.33 ± 12.99) ng/L (t = 7.72, P < 0.05 ). The level of IL-4 in the plasma of ITP was (7.42 ± 1.50) ng/L, which was lower than controls ( 18.17 ± 5.19) ng/L ( t = 12.87, P ＜ 0.05 ). Both IFN-γand T-bet mRNA levels were up-regulated in active ITP patients by the factor ( 8.57 ± 3.44 ) -fold and (3.34 ± 1.32)-fold than control group (t = 13.21,6.41 ,P <0.05). The decreases observed in IL-4 and Tim-3 were (0.25 ±0.15 )-fold and (0.29 ±0.15)-fold respectively in ITP patients compared with control group (t=10.02,9.61,P＜0.05 ). Conclusion The imbalance of Th17/Treg and the decrease of Tim-3 might be important determinants in the evolution of ITP.

Objective: To investigate the role of indoleamine 2, 3-dioxygenase in the development of uterine cervical squamous carcinoma. Methods: From January 2008 to December 2008, 116 uterine cervical carcinoma specimens and 18 metastatic lymph node specimens from patients with CIN Ⅰ-Ⅲ and uterine cervical squamous carcinoma were evaluated for iDO expression by immunohistochemistry. Twenty normal cervical specimens and 20 normal lymph node specimens were used as the controls. Results: The expression of IDO was not found in normal cervix and CIN Ⅰ. In CIN Ⅱ, IDO expres-sion was weakly positive in 2 cases (2/10, 20%) and negative in 8 cases (8/10, 80%). In CIN Ⅲ, IDO expression was weak-ly positive in 8 cases (8/13, 61.5%), positive in 1 case (1/13, 7.7%) and negative in 4 cases (4/13, 30.8%). The positive ex-pression rate of IDO in cervical cancer stage Ⅰ -Ⅳ was 100% (83/83). In cervical cancer stage Ⅰ A and Ⅰ B, the positive ex-pression rate of IDO was significantly higher than that in CIN Ⅱ and CIN Ⅲ (P<0.01). The positive expression rate of IDO in cervical cancer stage Ⅱ A-Ⅳ B was significantly higher than that in Ⅰ A and Ⅰ B. IDO expression was associated with cervi-cal cancer progression (OR=0.807, P<0.01). IDO expression in primary lesions with lymph node metastasis was significant-ly higher than that in those without lymph node metastasis. IDO expression rate was 100% in metastatic lymph nodes. The IDO expression was not associated with cervical squamous carcinoma differentiation degree (OR=-0.139,P>0.05). Conclu-sion: In CIN Ⅱ, escape mechanisms that stimulate cervical squamous carcinoma progression is gradually developed. IDO expression in metastatic lymph nodes is possibly associated with immune tolerance. IDO expression is not associated with differentiation degree of cervical squamous carcinoma. IDO may be a prognostic factor for uterine cervical squamous carci-noma and a therapeutic target for treatment.