Application progress of artificial intelligence in the screening and identification of drug targets / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has developed rapidly, with improved computing power and algorithms, which has greatly facilitated the collection and processing of biological, chemical information and clinical data, injecting new vitality into the research and development of new drugs.In this review, we began with a brief overview of the development and the main algorithms of AI in drug discovery.Then we elaborated through several specific cases on the various scenarios of AI application, including target identification, protein structure prediction, hit generation and optimization etc.Finally, we focused on a recent example to discuss the high efficiency of "end-to-end" application of AI.

Regulatory status and research progress in the supervision of cannabinoid compounds in food in some countries and regions / 上海预防医学

A group of compounds structurally related to tetrahydrocannabinol or capable of binding to cannabinoid receptors are collectively referred to as cannabinoids. Cannabinoids can be divided into plant derived cannabinoids， synthetic cannabinoids， and endogenous cannabinoids. Δ-9-THC is the only psychoactive compound in plant cannabinoids. Cannabis with Δ-9-THC>0.3% is internationally listed as a prohibited drug， while cannabis with Δ-9-THC<0.3% is industrial cannabis. Due to its low addiction and high commercial value， it is allowed to be added to food in many countries. More and more industrial cannabis foods become popular， and the detection/analysis of cannabinoid compounds in cannabis foods is particularly important； In addition to industrial cannabis， which is widely used in food， there are also various new drugs， synthetic cannabinoids， disguised as conventional food， which can cause the social problems and increase the food safety risks. This article will elaborate on the regulatory status of cannabinoid compounds in food， In order to promote the safety supervision of the domestic cannabis food.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Uncertainty evaluation for determination of anesthetics residues and their metabolites in aquatic products by high-performance liquid chromatography-tandem mass spectrometry / 上海预防医学

ObjectiveThe study aimed to evaluate the measurement uncertainty in the determination of five cacaine anesthetics and their metabolites residues by high-performance liquid chromatography-tandem mass spectrometry （LC-MS/MS）. MethodsThrough the establishment of mathematical model， the sources of uncertainty were analyzed， and various components were quantified and synthesized to evaluate the influence of the uncertainty components on the measurement results． ResultsThe uncertainties of the experiments were mainly derived from calibration curve fitting， sample pretreatment， recovery rate， standard solution preparation and measurement repeatability. Furthermore， the expanded uncertainty related to the content in shrimp （k=2） was 1.18 μg‧kg-1 at 8.68 μg‧kg-1 for tricaine methanesulfonate （MS-222）， 1.28 μg‧kg-1 at 9.11 μg‧kg-1 for benzocaine， 13.5 μg‧kg-1 at 91.4 μg‧kg-1 for 4-aminobenzoic acid， 12.2 μg‧kg-1 at 91.0 μg‧kg-1 for p-acetylamino benzoic acid， and 11.3 μg‧kg-1 at 95.3 μg‧kg-1 for 3-aminobenzoic acid， respectively. ConclusionThis method is suitable for the uncertainty analysis of cacaine anesthetics and their metabolites determination in aquatic products by LC-MS/MS， and can provide scientific and reliable basis for the measurement accuracy.

High-throughput screening of drug residues in aquatic products by liquid chromatography-electrostatic field track well high resolution mass spectrometry / 上海预防医学

ObjectiveIn order to ensure the food safety of cultured aquatic products in China， strengthen the supervision and improve detection efficiency， a high-throughput screening method for drug residues in aquatic products by mass spectrometry is to be developed. MethodsLiquid chromatography-electrostatic field track well high resolution mass spectrometry and C18 column were used to separate and collect the information of ion fragments and retention time of 195 veterinary drug standards in positive ion mode， and drug residues in aquatic products were extracted by organic solvents. ResultsThe mass spectrum database and detection methods of 195 veterinary drug standards were established， and a pre-treatment method was developed for extracting veterinary drug residues from aquatic products by acetonitrile and ethyl acetate. The detection method was sensitive， accurate， simple and rapid， and the adding standard recovery of more than 80% compounds reached 70%‒110%. ConclusionThe establishment of this method can quickly and massively screen drug residues in aquatic products， provide technical support for food safety risk monitoring and supervision， cope with the increasing demand for aquatic products and aquaculture volume year by year， and provide a theoretical basis for the subsequent development of mass spectrometry high-throughput detection methods.

Clinical observation of electroacupuncture with different frequencies for migraine without aura / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of electroacupuncture (EA) with different frequencies in treating migraine.Methods: Ninety patients with migraine were divided into a low frequency electroacupuncture (LF-EA) group, a high frequency electroacupuncture (HF-EA) group and a variable frequency electroacupuncture (VF-EA) group by the random number table method. Shuaigu (GB 8), Hegu (LI 4), Waiguan (TE 5), Taichong (LR 3), Taiyang (EX-HN 5), Fengchi (GB 20) and Ashi points were selected for all three groups. After achieving needling sensation (Deqi), the LF-EA group received 2 Hz continuous wave EA stimulation; the HF-EA group received 100 Hz continuous wave EA stimulation, and the VF-EA group received 2 Hz/100 Hz sparse-dense wave EA stimulation. The EA stimulation lasted for 30 min in all the three groups, once a day, 10 times as a course, and the clinical efficacy was evaluated after 2 consecutive courses of treatment. Results: After treatment, the total effective rates in the LF-EA group, HF-EA group and VF-EA group were 77.7％, 83.3％ and 93.3％, respectively. The difference in total effective rate between the LF-EA and HF-EA groups was not statistically significant (P>0.05), but the total effective rate was significantly higher in the VF-EA group than in the LF-EA and HF-EA groups (both P<0.01). After treatment, the headache scores significantly decreased in all three groups (all P<0.01). The difference in headache score between the LF-EA and HF-EA groups was not statistically significant (P>0.05), while the score was significantly lower in the VF-EA group than in the LF-EA and HF-EA groups (both P<0.01). Conclusion: VF-EA (2 Hz/100 Hz), compared with LF-EA (2 Hz) and HF-EA (100 Hz), shows superior clinical efficacy in treating migraine.

Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation / 中国实验方剂学杂志

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （<italic>P</italic><0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （<italic>P</italic><0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （<italic>P</italic><0.01）， and scores of three symptom dimensions were lower than those in control group （<italic>P</italic><0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （<italic>P</italic><0.01）， and CD8⁺ was lower than those in the control group （<italic>P</italic><0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-<italic>β</italic>₁ were lower than those in the control group （<italic>P</italic><0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （<italic>χ</italic>²=4.572， <italic>P</italic><0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Voluntary counseling and testing among young students in Hangzhou City during 2016-2020 / 中国学校卫生

Objective@#To analyze the characteristics of young students inquiry to voluntary counseling and testing (VCT) clinics, and to provide reference for AIDS prevention and control effectiveness of local schools.@*Methods@#A total of 1 223 students aged 7-28 years were collected and characterized through HIV Testing Consulting Information Management System in Shangcheng VCT clinics during 2016-2020. The epidemic characteristics were analyzed by cross sectional studies.@*Results@#Young students accounted for 25.21%(1 223/4 852) of the total counseling population in VCT clinics from 2016 to 2020. The main reason for counseling was non high risk (28.29%, 346 cases), followed by MSM (26.41%, 323 cases) and non commercial non fixed heterosexual behavior(25.92%, 317 cases). The counseling proportion of non commercial non fixed heterosexual behavior and commercial heterosexual sex behavior declined with time( χ 2 trend =-6.04, -3.59, P <0.01). The average of HIV positive detection rate among young students was 3.03%(37 cases), which increased with time( χ 2 trend=2.45, P <0.01).@*Conclusion@#Sex education and HIV/AIDS knowledge education are necessary in primary and secondary schools. Targeted strategies are in great need in terms of MSM behavior intervention.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Comparative analysis of the detection and control standards for quinolone residues in animal-derived foods and supervision among multiple regulatory sectors / 上海预防医学

In order to compare the standards for quinolone residues in animal-derived food in China and supervision among multiple regulatory sectors， we summarized and compared the current standards for the limits of quinolone residues in animal-derived food in China and sampling examination strategy among regulatory sectors. There were defects in the standard limits of lomefloxacin， pefloxacin， ofloxacin， and norfloxacin which have been banned by the Ministry of Agriculture and Rural Affairs. In addition， the determination limits of those indexes in the supervision remain inconsistent across multiple regulatory sectors. Multiple regulatory sectors on food safety should perform further risk assessment on the above problems and formulate the standards for the limits of quinolone residues in animal-derived food that may be applicable in China.

Analysis of factors related to puerperal infection in eastern Henan province / 中国基层医药

Objective:To explore and analyze the high risk factors of puerperal infection in eastern He'nan province, and to provide scientific basis for prevention of postpartum infection.Methods:The clinical data of 1 521 cases of puerpera in the First People's Hospital of Shangqiu and the People's Hospital of Xiayi County from August 2014 to October 2018 were retrospectively analyzed.Of the 1 521 cases, 91 cases with puerperal infection were enrolled in puerperal infection group, and 1 430 patients without puerperal infection were enrolled in puerperal uninfected group.The correlation of perineum incision, amniotic fluid contamination, soft birth canal injury, prenatal anemia, mode of delivery, placental residual, hemoglobin, birth process time, rupture time and bedtime with puerperal infection was explored.Results:The puerperal infection was associated with perineal incision, amniotic fluid contamination, prenatal anemia, postpartum hemorrhage, delivery mode and placental residue(χ 2=6.439, 5.269, 10.188, 4.862, 4.125, 6.663, all P<0.05). The duration of membrane rupture, hemoglobin, length of labor and bed rest in the puerperal infection group were (10.1±2.1)h, (110.5±10.8)g/L, (8.2±1.4)h, (2.8±0.6)d, respectively, which in the non-infection group were (11.2±2.5)h, (103.2±12.1)g/L, (11.7±1.8)h, (4.2±0.7)d, respectively, the differences between the two groups were statistically significant( t=-4.786, 6.205, -22.689, -21.355, all P<0.05). Conclusion:There are many factors that can cause puerperal infection, we should take preventive measures to against these risk factors in clinical practice, and to reduce the incidence of postpartum infection.

Research progress of orexin receptor antagonist in the treatment of insomnia / 中国基层医药

In recent years, drug therapy for insomnia has become a challenge for researchers around the world.The conventional therapeutic agents for the treatment of insomnia are benzodiazepine(BZD) and non-BZD(also known as z-drug), tricyclic antidepressants(TCA) doxepin and melatonin agonists.But because of the significant side effects of these drugs(eg.hangover, dependency, tolerance, rebound, insomnia, respiratory depression, respiratory dysfunction, cognitive dysfunction and increased anxiety), their potential to solve sleep problems is limited.Recent studies have shown that orexin-like neuropeptides are a factor in regulating the transition between awakening and sleep, helping to switch from a transitional state to a conscious state as a possible therapeutic target for the treatment of sleep disorders, with less side effects than conventional therapy.This review focuses on the progress of orexin receptor antagonists as a sleep drug.

Efficacy and Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Monocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute monocytic leukemia (AML-M5) and the related factors that affecting the prognosis of the patients.@*METHODS@#The clinical data of 71 patients with AML-M5 treated with allo-HSCT in Zhujiang Hospital Affiliated to Southern Medical University from April 2009 to October 2019 were collected and retrospectively analyzed. The incidence of graft-versus-host disease (GVHD), cumulative overall survival (OS) rate, cumulative progression-free survival (PFS) rate, transplantation-related mortality (TRM), relapse rate and the risk factors affecting prognosis in the patients were analyzed.@*RESULTS@#66 patients obtained hematopoietic reconstruction after transplantation, the median time of granulocyte implantation was 12 (9-26) d, and the median time of megakaryocytic implantation was 13 (8-72) d. The incidence of acute GVHD and chronic GVHD was 33.8% (24/71) and 36.6% (26/71), respectively. The median follow-up time was 13.81 (0.16 to 112.54) months; the median OS and PFS was 31.27 and 26.07 months, respectively. The cumulative OS of the patients in 1 and 3 years after transplantation was 64.9% and 48.6%, respectively, and the cumulative PFS of the patients in 1 and 3 years was 55.0% and 39.5%, respectively. The cumulative relapse rate of the patients in 1 and 3 years was 24% and 40%, respectively. Multivariate analysis showed that pre-transplantation relapse was the independent risk factor affecting OS (HR=2.32, 95%CI:1.17-4.62, P=0.02) and PFS (HR=3.08, 95%CI:1.61-5.90, P=0.001) of the patients; invasive fungal disease after transplantation was the independent risk factor affecting OS (HR=2.71, 95% CI:1.32-5.56, P=0.007) and PFS (HR=2.87, 95%CI=1.40-5.86, P=0.004) of the patients; FLT3 mutation was the independent risk factor affecting PFS (HR=2.13, 95%CI=1.07-4.24, P=0.03) of the patients.@*CONCLUSION@#AML-M5 is the intermediate or high-risk leukemia, and allo-HSCT can improve the survival prognosis of the patients. Pre-transplantation relapse and invasive fungal disease after transplantation are the important factors affecting the efficacy of allo-HSCT in patients with AML-M5.

Comprehensive performance evaluation of immunocolloidal gold qualitative rapid detection kits based on AHP-FCE method / 上海预防医学

Objective To establish a scientific and objective evaluation model of the comprehensive performance of immunocolloidal gold qualitative rapid detection kits, and to provide a reference for the overall evaluation of similar products. Methods Based on the various factors affecting the performance of qualitative rapid detection kits, a comprehensive performance evaluation index system consisting of 4 first-level indicators and 18 second-level indicators was constructed.The analytic hierarchy process (AHP) and the fuzzy comprehensive evaluation (FCE) method were combined to determine the weights for the evaluation indicators and graded thresholds.The model was then used to evaluate the performance level of 6 brands of furazolidone metabolite rapid test kits. Results According to maximum membership degree principle, the evaluation of brand A, B, C, D, E and F were graded as good, excellent, middle, excellent, middle and excellent, respectively.Then the scores of 6 brands were calculated according to the hundred-mark system, and brand B had the highest score.This was consistent with the actual use experience. Conclusion The application of this model can make the evaluation results more comprehensive and accurate, providing reference for rational evaluation and selection of qualitative rapid detection kits.

Application progress of intelligentialized technology in food safety supervision / 上海预防医学

The paper deals with the application of intelligentialized technology in food safety supervision, and analyzes the progress in application of the technology.By comparing with the traditional supervision mode, advantages and deficiencies of intelligentialized technology in the food safety supervision are illustrated.It is concluded that the intelligentialized technology will absolutely serve as a good way of the technical support to solve food safety problems in China in the future.

The inhibition mechanism of the uptake of lamivudine via human organic anion transporter 1 by Stellera chamaejasme L. extracts / 中国天然药物

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC) and maximal plasma concentration (C) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.

Expression and significance of hypoxia-inducible factor-1α and vascular endothelial growth factor and receptor 2 in stage 3 pressure injury of rats / 中国应用生理学杂志

OBJECTIVE@#To analyze the expression and relationship of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR) in local skin tissues of pressure injury and investigate the possible mechanism of stage 3 pressure injury refractory wound.@*METHODS@#Forty male SD rats were randomly divided into normal control group, compressed 3 d, 5 d, 7 d, and 9 d groups. Stage 3 pressure injury animal model were established by magnet compression. The morphology of skin was observed by HE staining. The expression of VEGF was detected by immunohistochemistry. The expression levels of HIF-1α, VEGF and KDR protein in skin tissue were detected by Western blot. One-way analysis of variance and LSD test were performed on the data.@*RESULTS@#①The HE results showed that compared with the normal control group, the epidermis of the compressed group was gradually thickened, the number of blood vessels was decreased, the collagen arrangement disordered and inflammatory cells infiltration were increased. ②Immunohistochemical results showed that the expression of VEGF protein in the 3 d group was significantly higher than that in the normal control group (P＜0.01). The expression of VEGF protein in the skin tissue of 5 d, 7 d and 9 d groups was lower than that in normal control group (P＜0.05). WB results were consistent with immunohistochemistry results. ③WB results showed that the expression of HIF-1α in the skin tissues of the rats in 3 d, 5 d and 7 d groups was higher than that in the normal control group (P＜0.01 or P＜0.05). The expression of KDR protein was lower than that of the normal control group (P＜0.05 or P＜0.01).@*CONCLUSION@#HIF-1α mediated reduction of VEGF and KDR protein expression and decreased tissue angiogenesis may be one of the important causes of chronic dysfunction of stage 3 pressure injury.

Research Progress and Forensic Identification of Alcoholic Cardiomyopathy / 法医学杂志

With the rapid development of the social economy in China, the incidence of diseases caused by excessive drinking is gradually increasing as well. Alcoholic cardiomyopathy refers to long-term high intake of ethanol, and has typical dilated cardiomyopathy characteristics, such as, hemodynamic changes, symptoms, signs, and morphological features. It is a kind of cardiomyopathy that excludes other causes of dilated cardiomyopathy. Due to the lack of specific pathological changes, the forensic pathological identification of alcoholic cardiomyopathy can only be based on the patient's medical history and by ruling out other causes of cardiomyopathy. This paper reviews the pathogenesis and forensic identification of alcoholic cardiomyopathy in order to provide reference for forensic pathologists and clinicians.

Anti-arrhythmic effects of taurine-magnesium coordination compound on torsades de pointes / 中国应用生理学杂志

OBJECTIVES@#To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.@*METHODS@#Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose.@*RESULTS@#Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group.@*CONCLUSIONS@#TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).

Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D).</p><p><b>METHOD</b>A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests.</p><p><b>RESULTS</b>A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant.</p><p><b>CONCLUSION</b>Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).</p>