Objective To clarify the anti-fibrotic effect of hypericin on preventing renal fibrosis.To explore if hypericin can improve renal tubulointerstitial fibrosis by inhibiting the Yes-associated protein(YAP).Methods Thirty-six male mice were randomly allocated into 6 groups(n=6 per group):sham group,sham+hypericin(120 mg/kg)group,UUO model group,hyperi-cin(30,60,120 mg/kg)treatment groups.Except for the sham group,renal interstitial fibrosis was induced in all other groups via unilateral ureteral obstruction(UUO).Mice in the hypericin treatment group received corresponding doses of hypericin sus-pension via oral gavage,while sham group and UUO model group were administered equivalent volumes of normal saline through the same route for 14 consecutive days.Additionally,an in vitro model was established using NRK-52E cells treated with TGF-β1(10 ng/mL).To evaluate the anti-fibrotic effects of hypericin,protein expression levels of α-SMA,fibronectin,col-lagen Ⅰ and collagen Ⅲ were assessed in both the UUO mouse kidney tissues and TGF-β1-stimulated NRK-52E cells using Western blotting.Blood urea nitrogen(BUN)and creatinine(Cr)levels in mice were measured to assess the renal protective effects of hypericin.Histological changes and collagen deposition in the kidneys were observed using hematoxylin-eosin and Masson staining.The expression levels of YAP and its downstream target gene CTGF were also determined using Western blot-ting.The specific mechanism of hypericin in improving renal interstitial fibrosis was further explored using the YAP inhibitor verteporfin.Results The protein expression levels of α-SMA,FN,collagen Ⅰ,and collagen Ⅲ in renal tissues of UUO mice and TGF-β1-induced NRK-52E cells were markedly reversed by hypericin(all P＜0.01).The levels of Cr and BUN in UUO mice se-rum were effectively reduced(both P＜0.01),and renal histopathological alterations and interstitial collagen deposition were markedly ameliorated.Potent inhibitory effects on YAP and CTGF protein expression were observed both in vivo and in vitro(both P＜0.01),exhibiting similar effects to verteporfin.Both treatments dramatically reduced TGF-β1-induced fibrosis in NRK-52E cells.Conclusion Hypericin can inhibit renal tubulointerstitial fibrosis by inhibiting YAP.

Objective To clarify the anti-fibrotic effect of hypericin on preventing renal fibrosis.To explore if hypericin can improve renal tubulointerstitial fibrosis by inhibiting the Yes-associated protein(YAP).Methods Thirty-six male mice were randomly allocated into 6 groups(n=6 per group):sham group,sham+hypericin(120 mg/kg)group,UUO model group,hyperi-cin(30,60,120 mg/kg)treatment groups.Except for the sham group,renal interstitial fibrosis was induced in all other groups via unilateral ureteral obstruction(UUO).Mice in the hypericin treatment group received corresponding doses of hypericin sus-pension via oral gavage,while sham group and UUO model group were administered equivalent volumes of normal saline through the same route for 14 consecutive days.Additionally,an in vitro model was established using NRK-52E cells treated with TGF-β1(10 ng/mL).To evaluate the anti-fibrotic effects of hypericin,protein expression levels of α-SMA,fibronectin,col-lagen Ⅰ and collagen Ⅲ were assessed in both the UUO mouse kidney tissues and TGF-β1-stimulated NRK-52E cells using Western blotting.Blood urea nitrogen(BUN)and creatinine(Cr)levels in mice were measured to assess the renal protective effects of hypericin.Histological changes and collagen deposition in the kidneys were observed using hematoxylin-eosin and Masson staining.The expression levels of YAP and its downstream target gene CTGF were also determined using Western blot-ting.The specific mechanism of hypericin in improving renal interstitial fibrosis was further explored using the YAP inhibitor verteporfin.Results The protein expression levels of α-SMA,FN,collagen Ⅰ,and collagen Ⅲ in renal tissues of UUO mice and TGF-β1-induced NRK-52E cells were markedly reversed by hypericin(all P＜0.01).The levels of Cr and BUN in UUO mice se-rum were effectively reduced(both P＜0.01),and renal histopathological alterations and interstitial collagen deposition were markedly ameliorated.Potent inhibitory effects on YAP and CTGF protein expression were observed both in vivo and in vitro(both P＜0.01),exhibiting similar effects to verteporfin.Both treatments dramatically reduced TGF-β1-induced fibrosis in NRK-52E cells.Conclusion Hypericin can inhibit renal tubulointerstitial fibrosis by inhibiting YAP.

Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.

Objective    To investigate the clinical safety and feasibility of thoracic sympathectomy in the treatment of palmar hyperhidrosis based on ambulatory surgery. Methods    A retrospective analysis of 74 patients who underwent thoracoscopic sympathectomy in the Department of Thoracic Surgery of the First People's Hospital of Yunnan Province from January 2017 to April 2021 was performed, including 35 males and 39 females aged 12-38 (21.32±4.13) years. Patients were divided into two groups according to different treatments. There were 34 patients in a control group (adopting traditional surgery), and 40 patients in an observation group (adopting ambulatory surgery). The clinical effects of the two groups were compared. Results    No massive bleeding, conversion to thoracotomy, postoperative pneumo-thorax or severe pneumonia occured in all patients. Univariate analysis of intraoperative indexes showed that the two groups had no statistical difference in total hospitalization cost, operation time, anesthesia time or postoperative waiting time (P>0.05). The amount of intraoperative blood loss in the observation group was less than that in the control group (P<0.05). The time of postoperative out of bed and recovery of walking capacity and the incidence of electrolyte disturbance in the observation group were shorter or lower than those in the control group (P<0.05). There was no statistical difference in white blood count, neutrophils count or postoperative 24 h pulse oxygen saturation fluctuation peak between the two groups (P>0.05). Conclusion    Based on the optimized diagnosis and treatment model, thoraco-scopic sympathectomy with laryngeal mask airway which is performed during ambulatory surgery, is feasible and worth popularizing in thoracic surgery.

Objective    To investigate the feasibility and safety of non-intubation anesthesia in thoracic surgery. Methods    From September 2017 to December 2019, 296 patients were operated at department of thoracic surgery in our hospital. There were 167 males and 129 females with an average age of 50.69±12.95 years, ranging from 16 to 76 years. The patients were divided into two groups according to whether they were intubated: 150 patients were in a non-intubation group, including 83 males and 67 females with an average age of 49.91±13.59 years, ranging from 16 to 76 years, and 146 patients were in an intubation group including 84 males and 62 females with an average age of 51.49±12.26 years, ranging from 16 to 74 years. Intraoperative data, postoperative recovery, inflammatory response of the two groups were compared. Results    There was no statistical difference between the two groups in operation time, blood loss, the lowest oxygen saturation or other indicators (P>0.05). But the highest partial pressure of carbon dioxide of the non-intubation group was higher than that of the intubation group (P=0.012). The non-intubation group was superior to the intubation group in postoperative recovery and inflammatory response (P<0.05). Conclusion    The non-intubation anesthesia is safe and maneuverable in thoracic surgery, and it has some advantages in accelerating postoperative rehabilitation.

Objective:To investigate the levels of urinary arsenic metabolites in arsenic-exposed people with different degrees of skin lesions.Methods:A cluster sampling method was used to select people with different degrees of skin lesions in the drinking water arsenic poisoning area of Bayannaoer City, Inner Mongolia Autonomous Region. According to the "Standard of Diagnosis for Endemic Arsenism" (WS/T 211-2001), the research subjects were divided into four clinical grading: normal, suspicious, mild, moderate and above on the basis of the degrees of skin lesions. Urine samples from any 1 middle section were collected, and the levels of urinary arsenic metabolites of different forms in different clinically graded people were detected by inductively coupled plasma mass spectrometry (ICP-MS).Results:A total of 522 people were included, including 309 males and 213 females; the age was (39.11 ± 12.38) years old, ranging from 11 to 65 years old. There were 337, 80, 31, 74 people in normal, suspicious, mild, moderate and above clinical grading, the levels of inorganic arsenic (iAs, medians: 15.46, 37.16, 104.46, 163.06 μg/L), monomethylarsonic acid (MMA, medians: 15.95, 33.27, 82.80, 123.84 μg/L), dimethylarsenic acid (DMA, medians: 78.16, 147.86, 301.28, 371.30 μg/L), total arsenic (tAs, medians: 113.90, 220.94, 501.25, 684.46 μg/L), iAs percentage (iAs%, medians: 15.66%, 15.53%, 21.67%, 21.65%), MMA percentage (MMA%, medians: 13.51%, 15.40%, 17.14%, 16.43%), DMA percentage (DMA%, medians: 70.37%, 67.98%, 63.25%, 61.23%), monomethylation rate (PMI, medians: 0.84, 0.84, 0.78, 0.78), dimethylation rate (SMI, medians: 0.84, 0.81, 0.79, 0.79), and ratio of MMA to DMA (MMA/DMA, medians: 0.20, 0.23, 0.27, 0.27) were compared in different clinically graded people, the differences were statistically significant ( H = 97.98, 96.44, 85.50, 95.08, 38.58, 29.94, 51.98, 38.58, 43.20, 43.20, P < 0.01). Compared with normal people, iAs, MMA, DMA, tAs, MMA%, and MMA/DMA levels significantly increased, and SMI level significantly decreased in suspicious, mild, moderate and above people ( P < 0.017); compared with normal people, iAs% level significantly increased, and DMA% and PMI levels significantly decreased in mild, moderate and above people ( P < 0.017). Conclusion:The levels of urinary arsenic metabolites in arsenic-exposed people with different degrees of skin lesions are different, showing a dose-response relationship.

Objective To investigate the arsenic methylation level of people chronically exposed to different levels of arsenic in drinking water.Methods A cluster sampling method was used to select 874 cases that had drank different concentration arsenic-contaminated water from arsenic endemic area in Bayannaoer City.They were divided into four groups according to arsenic exposure level:control (≤ 10 μg/L),low (＞ 10-50 μg/L),medium (＞ 50-200 μg/L) and high groups (＞ 200 μg/L),146,155,224,349 cases,respectively.The content of arsenic in drinking water and the arsenic species in urine were analyzed by inductively coupled plasma mass spectrometry (ICPMSS) and the results were expressed as median.Results The inorganic arsenic (iAs),monomethylarsonic acid (MMA),dimethylarsinic acid (DMA),and total-arsenic (tAs) in urine of low,medium and high groups increased following increasing of arsenic exposure level (x2 =605.08,609.96,615.83,628.64,all P ＜ 0.017) and iAs％,MMA％ and MMA/DMA significantly increased following increasing of arsenic exposure level (x2 =112.30,56.60,86.47,all P ＜ 0.017).DMA％,PMI and SMI significantly decreased following increasing of arsenic exposure level (x2 =125.80,112.30,86.47,all P ＜ 0.017).In the four groups,iAs％ of female were 11.39％,12.28％,13.47％ and 17.58％,they were significantly lower than those of male's (15.52％,16.19％,17.45％,21.86％,Z =-4.22,-3.79,-4.60,-6.71,all P ＜ 0.05);and DMA％ were 76.95％,74.05％,72.76％,and 68.64％ in the four groups respectively,and the PMI of female were 0.89,0.88,0.87,and 0.82,both DMA％ and PMI were significantly higher than those of male in each group (71.17％,69.39％,67.36％,61.29％,0.84,0.84,0.83,0.78,Z =-4.00,-3.34,-5.50,-7.24,-4.22,-3.79,-4.60,-6.71,all P ＜ 0.05).In control group,arsenic metabolites levels of people were not significantly different in the three age groups (all P ＞ 0.05).Compared to the ≤30 age group,the MMA,DMA and tAs of 31-45 age group increased and DMA,DMA％,PMI of ≥46 age group increased while iAs％ decreased in high group (μg/L:72.71 vs 109.13,307.90 vs 419.50,505.59 vs 684.60,307.90 vs 418.26;64.31％ vs 68.45％,0.79 vs 0.83,20.71％ vs 17.35％,x2 =10.72,10.24,8.20,10.24,9.89,20.96,20.96,all P ＜ 0.017).Compared to the 31-45 age group,DMA％ and PMI of ≥46 age group increased while iAs％ decreased (64.91％ vs 68.45％,0.80 vs 0.83,20.14％ vs 17.35％,x2 =9.89,20.96,20.96,all P ＜ 0.017).Conclusion There is a significant dose response relationship between arsenic metabolites and arsenic exposure level,and arsenic methylation is related to gender and age.

Objective To study the relationship between hair selenium content and arsenism among population from endemic arsenism area caused by coal combustion in the southern of Shaanxi Province.Methods Four high-arsenic-exposed villages in southern Shaanxi Province were selected as the study area,and the nonarsenic-exposed villages nearby were selected as the control area,90 hair samples of residents exposed to high arsenic in the study area and 14 hair samples of residents in the control area were collected.Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the contents of arsenic and selenium in hair samples.Selenium/hair arsenic (Se/As) value was calculated,and the relationship between selenium content in hair samples and arsenicosis was analyzed.Results The geometric mean of selenium concentration in hair from the study area was 8.72 mg/kg,which was significandy higher than that from the control area (0.54 mg/kg,t =9.811,P ＜ 0.05).However,selenosis case was not found in the study area.Selenium content in hair was not obviously correlated with arsenism (r =0.075,P ＞ 0.05),while the Se/As value was negatively associated with the grade of arsenism (P ＞ 0.05).The geometric mean of selenium content in hair of female from the study area was 12.79 mg/kg,which was higher than that in hair of male (6.5 mg/kg,t =1.738,P ＜ 0.01).Meanwhile,the Se/As value in hair of female from the study area (1.15) was significantly higher than that in hair of male (0.65,t =3.218,P ＜ 0.05).Conclusions The environment of the study area is polluted by arsenic and selenium derived from stone-coal burning.Antagonism between arsenic and selenium might reduce the toxicity of selenium.Therefore,selenosis is not found in the study area.In addition,antagonism between arsenic and selenium might also induce lower prevalence of arsenism for female in the studly area.

[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.

Basic knowledge of forensic science is theoretical and abstract,therefore,confir-matory experiment teaching is often adopted in the experiment teaching. International education has become an important topic in medical colleges and universities. Forensic medicine is a compulsory subject for medical international students. This article discussed the exploration and practice in teach-ing forensic medicine for international students at Wenzhou Medical University,which included faculty constructing and training,encouraging whole English teaching by young teachers,applying heuristic interactive teaching and case teaching,establishing strict attendance and appraisal system and con-ducting comprehensive evaluation on medical teaching quality and teaching management.