Risk of skin cancer in kidney, liver and heart recipients: A nationwide population-based study in Taiwan

Background: Previous population-based studies in western countries had revealed increased skin cancer risk among transplant recipients compared to the general population. However, population-based studies in Asia on skin cancer among recipients of different transplanted organs were lacking in the literature. Aims: This study aims to estimate skin cancer risk among recipients in Taiwan, examine the association between each specific type of skin cancer and each type of transplanted organ, and compare skin cancer risk between different immunosuppressive regimens. Methods: This population-based retrospective cohort study identified 7550 patients with heart, lung, kidney or liver transplantation and 30,200 controls matched for gender, age and comorbidity index from the National Health Insurance Research Database in Taiwan between 2000 and 2015. Using multivariable Cox proportional hazard models, we estimated the hazard ratios and 95% confidence intervals for the correlation of skin cancer with organ transplantation as well as immunosuppressive regimen. Results: Organ transplant recipients in Taiwan had an increased risk of skin cancer with adjusted hazard ratios of 4.327 (95% confidence intervals 2.740–6.837, P < 0.001), with the greatest risk, observed among heart recipients (adjusted hazard ratios 6.348, 95% confidence intervals 3.080–13.088, P < 0.001). The risk of non-melanoma skin cancer and melanoma was 4.473 (95% confidence intervals 2.568–7.783, P < 0.001) and 3.324 (95% confidence intervals 1.300–8.172, P < 0.001), respectively. When comparing immunosuppressants, those with calcineurin inhibitors carried the highest risk of skin cancer (adjusted hazard ratios 4.789, 95% confidence intervals 3.033–7.569, P < 0.001), followed by those with antimetabolites (adjusted hazard ratios 4.771, 95% confidence intervals 3.025–7.541, P < 0.001). Limitations: We could not evaluate confounding behavioural risk factors of skin cancers that were not documented in the database, nor could we recognize patients’ compliance with immunosuppressants. Conclusion: Organ recipients have a greater risk of skin cancer. Clinicians should inform recipients of the importance of photoprotection and regular dermatologic follow-up

Effect of serine protease inhibitor Kazal-type 1 on the proliferation of hepatocellular carcinoma cell and its mechanism / 解剖学报

[Abstract] Objective To explore the effect of serine protease inhibitor Kazal-type 1(SPINK1) on the proliferation of hepatocellular carcinoma cells RH-35 and its underling molecular mechanism. Methods Spink1 gene expression in liver cancer and rat liver cancer models were analyzed by Gene Expression Omnibus (GEO) data, RH-35 cells were treated with rrSPINK1 protein, the effect of rrSPINK1 on the proliferation and apoptosis of RH-35 cells was explored by MTT, 2’-deoxy-5-ethynyluridine(EdU) and flow cytometry, the molecular mechanism of SPINK1 regulating liver cancer were detected by Real-time PCR and Western blotting. Results The results showed that Spink1 gene was over-expressed significantly in liver cancer and rat liver cancer models, rrSPINK1-treated RH-35 cells showed increased viability, EdUpositive cell rate, and the proportion of cells in S phase and G

Metabolomics study of corn silk on renal tissue and urine of diabetic nephropathy rats / 中国药理学通报

Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy (DN) rats using metabolomics technology. Methods DN rat model was established by feeding with high-sugar and high-fat diet, combined with intraperitoneal injection of low dose streptozotocin. Renal organ index, fasting blood glucose, albumin creatinine ratio, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol indexes were measured, and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats. Further, UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine, combined with principal component analysis (PC A) and orthogonal partial least squares discriminant analysis (OPLS-DA). After identification by HM-DB and KEGG database, the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis. Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk, indicating that corn silk had a good intervention effect on DN. Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk, and it involved 18 metabolic pathways mainly including phenylalanine, tyrosine and tryptophan biosynthesis, riboflavin metabolism, arachidonic acid metabolism, and tyrosine metabolism. Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism, riboflavin metabolism, and arachidonic acid metabolism.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Mapping out the surgical anatomy of the lingual nerve:a systematic review and meta-analysis

Objectives@#Understanding the lingual nerve’s precise location is crucial to prevent iatrogenic injury. This systematic review seeks to determine the lingual nerve’s most probable topographical location in the posterior mandible. @*Materials and Methods@#Two electronic databases were searched, identifying studies reporting the lingual nerve’s position in the posterior mandible.Anatomical data in the vertical and horizontal dimensions at the retromolar and molar regions were collected for meta-analyses. @*Results@#Of the 2,700 unique records identified, 18 studies were included in this review. In the vertical plane, 8.8% (95% confidence interval [CI], 1.0%-21.7%) and 6.3% (95% CI, 1.9%-12.5%) of the lingual nerves coursed above the alveolar crest at the retromolar and third molar regions. The mean vertical distance between the nerve and the alveolar crest ranged from 12.10 to 4.32 mm at the first to third molar regions. In the horizontal plane, 19.9% (95% CI, 0.0%-62.7%) and 35.2% (95% CI, 13.0%-61.1%) of the lingual nerves were in contact with the lingual plate at the retromolar and third molar regions. @*Conclusion@#This systematic review mapped out the anatomical location of the lingual nerve in the posterior mandible, highlighting regions that warrant additional caution during surgeries to avoid iatrogenic lingual nerve injuries.

Curative effect of capreomycin in adjuvant treatment of multidrug-resistant pulmonary tuberculosis and its effect on quality of life and immune function / 中国热带医学

@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

Pregnancy-Associated Spontaneous Coronary Artery Dissection: A Case Report and the Lessons from Practice

@#Pregnancy-associated spontaneous coronary artery dissection (P-SCAD) is one of the fatal conditions that most commonly causes pregnancy-associated myocardial infarction. We herein report a case of P-SCAD in a 26-year-old multigravida woman, who complained of angina postpartum with raised cardiac biomarkers and transient ST-segment elevation on electrocardiograms. We emphasize the importance of a high degree of suspicion in the diagnosis of P-SCAD, together with the common presentation, the management approach, and its psychological impacts on the patients.

An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix / 中国中药杂志

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 μL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

Advances in peptidomimetic inhibitors of coronavirus main protease / 药学学报

Coronavirus (CoVs) is a widespread pathogen that can infect humans and animals to cause serious acute and chronic respiratory diseases. Among them, SARS-CoV broke out in 2003, MERS-CoV was discovered and spread widely in 2012, and SARS-CoV-2 emerged at the end of 2019. They all belong to β-coronavirus. Peptidomimetic inhibitors targeting coronavirus main proteases (Mpro, 3CLpro) have attracted much attention because of their broad spectrum and strong antiviral efficacy. In this review, peptidomimetic inhibitors of coronavirus main protease were classified and summarized according to the different "warheads" in design strategy. And also, the molecular structures, biological activity and design ideas of the inhibitors were analyzed and discussed, which is aimed to provide useful reference for further design and development of coronavirus inhibitors.

Preparation of purified proteins from fresh Pheretima and their inhibitory effect against pulmonary fibrosis in mice / 南方医科大学学报

OBJECTIVE@#To develop a convenient method for rapid purification of fresh Pheretima proteins and assess the inhibitory effect of these proteins against pulmonary fibrosis.@*METHODS@#The crude extract of fresh Pheretima was obtained by freeze-drying method and then purified by size exclusion chromatography. The composition of the purified proteins was analyzed by mass spectrometry. MRC-5 cells were treated with 5 ng/mL TGF-β1 alone (model group) or in combination with SB431542 (2 μmol/L) or the purified proteins (13.125 μg/mL), and the cytotoxicity of purified proteins and their inhibitory effects on cell proliferation were detected with CCK8 assay. Flow cytometry was used to detect the changes in cell apoptosis, and the cellular expressions of α-SMA, Vimentin, E-cadherin, collagen I, Smad2/3 and P-Smad2/3 were detected using RT-PCR and Western blotting. In the animal experiment, adult male C57BL/6 mice were subjected to intratracheal instillation of bleomycin followed by treatment with the purified proteins (5 mg/mL) for 21 days, after which HE and Masson staining was used to observe the pathological changes in the lung tissue of the mice.@*RESULTS@#We successfully obtained purified proteins from fresh Pheretima protein by size exclusion chromatography. Treatment with the purified proteins significantly inhibited TGF-β1-induced proliferation of MRC-5 cells (P < 0.01), reduced the cellular expressions of α-SMA, Vimentin and collagen I (P < 0.001 or P < 0.01), increased the expression of E-cadherin (P < 0.01), and inhibited the expressions of Smad2/3 and P-Smad2/3 (P < 0.001 or P < 0.01). In male C57BL/6 mice models of bleomycin-induced pulmonary fibrosis, treatment with the purified proteins obviously reduced the number of inflammatory cells and fibrotic area in the lungs.@*CONCLUSION@#The purified proteins from fresh Pheretima obtained by size exclusion chromatography can inhibit pulmonary fibrosis in mice by regulating the TGF-β/ Smad pathway.

Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy / 中华胃肠外科杂志

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

Research Advances in the Role of Keratins in Gastrointestinal Cancer / 中国医学科学杂志(英文版)

The incidence and mortality rates of gastrointestinal (GI) cancer remain high. Despite constant improvements in diagnostic and therapeutic techniques, the early diagnosis, mid- and late-stage treatment, drug tolerance, and cancer recurrence and metastasis in GI cancer remain challenging. In this review article we summarize the recent research advance in the roles of keratins in GI cancer, with the hope that they will become efficient biomarkers for the prediction, diagnosis, or treatment of these malignancies.

Pre- and apnoeic high-flow oxygenation for rapid sequence intubation in the emergency department (the Pre-AeRATE trial): A multicentre randomised controlled trial

INTRODUCTION@#Evidence regarding the efficacy of high-flow nasal cannula (HFNC) oxygenation for preoxygenation and apnoeic oxygenation is conflicting. Our objective is to evaluate whether HFNC oxygenation for preoxygenation and apnoeic oxygenation maintains higher oxygen saturation (SpO2) during rapid sequence intubation (RSI) in ED patients compared to usual care.@*METHODS@#This was a multicentre, open-label, randomised controlled trial in adult ED patients requiring RSI. Patients were randomly assigned 1:1 to either intervention (HFNC oxygenation at 60L/min) group or control (non-rebreather mask for preoxygenation and nasal prongs of at least 15L/min oxygen flow for apnoeic oxygenation) group. Primary outcome was lowest SpO2 during the first intubation attempt. Secondary outcomes included incidence of SpO2 falling below 90% and safe apnoea time.@*RESULTS@#One hundred and ninety patients were included, with 97 in the intervention and 93 in the control group. Median lowest SpO2 during the first intubation attempt was 100% in both groups. Incidence of SpO2 falling below 90% was lower in the intervention group (15.5%) compared to the control group (22.6%) (adjusted relative risk=0.68, 95% confidence interval [CI] 0.37-1.25). Post hoc quantile regression analysis showed that the first quartile of lowest SpO2 during the first intubation attempt was greater by 5.46% (95% CI 1.48-9.45%, P=0.007) in the intervention group.@*CONCLUSION@#Use of HFNC for preoxygenation and apnoeic oxygenation, when compared to usual care, did not improve lowest SpO2 during the first intubation attempt but may prolong safe apnoea time.

Time to initial diagnosis of imported malaria and its influencing factors in Jiangsu Province / 中国血吸虫病防治杂志

Objective To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. Methods The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. Results A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. Conclusions Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.

Fermented Cordyceps Powder Combined with ACEI/ARB in Treatment of Diabetic Kidney Disease： A Systematic Review / 中国实验方剂学杂志

［Abstract］Objective:To evaluate the efficacy and safety of fermented cordyceps powder combined with angiotensin-converting enzyme inhibitors （ACEI）/angiotensin Ⅱ receptor blocker （ARB） in the treatment of diabetic kidney disease （DKD）. Method:The randomized controlled trials （RCTs） concerning the treatment of DKD with fermented cordyceps powder plus ACEI/ARB were retrieved from Pubmed， Embase， Cochrane library， China National Knowledge Infrastructure （CNKI）， Chinese BioMedical Literature Database on disc （CBMdisc）， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）. The quality of the included articles was evaluated by the Cochrane Collaboration's tool， followed by data analysis using RevMan 5.3. Result:A total of 48 RCTs were included， involving 4 562 cases. As revealed by Meta-analysis， the effective rate of fermented cordyceps powder combined with ACEI/ARB was higher than that of ACEI/ARB ［risk ratio （RR）=1.20， 95% confidence interval （CI） （1.15，1.24）， <italic>P</italic><0.000 01］. Moreover， such combination effectively reduced urinary albumin excretion rate ［standardized mean difference （SMD）=-2.61，95%CI （-3.17，-2.05），<italic>P</italic><0.000 01］，24-h proteinuria［SMD=-1.75，95%CI （-2.15，-1.35），<italic>P</italic><0.000 01］， serum creatinine（Scr）［mean difference （MD）=-14.57，95%CI （-17.94，-11.21），<italic>P</italic><0.000 01］， blood urea nitrogen（BUN）［MD=-1.05，95%CI （-1.29，-0.81），<italic>P</italic><0.000 01］， cystatin C （Cys-C） ［MD=-0.52，95%CI （-0.68，-0.36），<italic>P</italic><0.000 01］， fasting blood glucose（FBG）［MD=-0.59，95%CI （-0.93，-0.25），<italic>P</italic>=0.000 6］， hemoglobin A1c（HbA1c）［MD=-0.50，95%CI（-0.75，-0.24），<italic>P</italic>=0.000 1］， tumor necrosis factor-<italic>α</italic>（TNF）-<italic>α </italic>［SMD=-1.68，95%CI （-2.21，-1.15），<italic>P</italic><0.000 01］， C-reactive protein（CRP） ［SMD=-1.35，95%CI （-1.77，-0.93），<italic>P</italic><0.000 01］， and interleukin-6 （IL-6） ［SMD=-1.52，95%CI （-1.98，-1.07），<italic>P</italic><0.000 01］. There was no significant difference in the incidence of adverse events between the two groups ［RR=0.77，95%CI （0.49，1.21），<italic>P</italic>=0.25］. Conclusion:Fermented cordyceps powder combined with ACEI/ARB is more effective than ACEI/ARB in the treatment of DKD， which is worthy of clinical promotion and use. More multi-center RCTs with a large sample size are needed for verification.

Effect and Mechanism of Shaofu Zhuyutang on Endothelial Injury of Rats with Cold Coagulation and Blood Stasis Syndrome Based on Nrf2/ARE Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Shaofu Zhuyutang on nuclear factor erythroid-2-related factor 2 （Nrf2） /antioxidant response element （ARE） signaling pathway in blood vessels by establishing the model of rats with cold coagulation and blood stasis syndrome， and to explore the protective effect and mechanism of Shaofu Zhuyutang on vascular endothelial injury. Method:The 50 SPF rats were randomly divided into high dose group （4.8 g·kg-1）， middle dose group （2.4 g·kg-1）， low dose group （1.2 g·kg-1）， model group and normal group （ten of each group）. The rat model of cold coagulation and blood stasis syndrome was established by subcutaneous injection of epinephrine hydrochloride combined with ice bath. At the same time of modeling， the drug was administered by gavage. After 28 days of continuous administration， the hemorheology indexes were detected by automatic hemorheology instrument. Levels of nitric oxide （NO）， endothelin （ET）-1， superoxide dismutase （SOD）， glutathione （GSH-Px）， intercellular adhesion molecule-1（ICAM-1）， vascular cell adhesion molecule-1（VCAM-1）， von Willebrand factor （vWF） in serum were determined by ELISA. Hematoxylin and eosin （HE） staining was used to observe the endothelial injury of vascular tissue of thoracic aorta. The protein expression of Nrf2 and HO-1 in vascular tissue of thoracic aorta was detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）was used to observe the expression of Nrf2 and heme oxygenase-1 （HO-1） mRNA in vascular tissue of thoracic aorta. Result:Compared with the blank group， model group rats whole blood viscosity and plasma viscosity were significantly increased （P<0.05，P<0.01）， vWF， ICAM 1， VCAM 1 content increased significantly （P<0.01）， NO， SOD， gsh-px levels decreased significantly （P<0.01）， significantly increased the content of ET-1（P<0.01）， thoracic aorta vascular tissue Nrf2， HO-1 mRNA expression was significantly increased （P<0.01）， Nrf2 protein expression in the cell nucleus increased significantly （P<0.05）， The protein expression level of Nrf2 in cytoplasm was significantly decreased （P<0.05）， while the protein expression level of HO-1 was significantly increased （P<0.01）. Compared with model group， the whole blood viscosity （high and middle cut）， plasma viscosity， were significantly reduced in high and meduim-dose Shaofu Zhuyutang groups（P<0.05，P<0.01）. The levels of vWF， ICAM-1， VCAM-1 and ET-1 in serum were significantly reduced （P<0.05，P<0.01）， NO， SOD and GSH-Px increased significantly （P<0.05，P<0.01）. The pathological changes such as hyperplasia， swelling and shedding of endothelial cells of thoracic aorta， rupture of internal elastic membrane and disorder of smooth muscle arrangement were improved. The expression levels of Nrf2， HO-1 protein and gene were significantly increased in vascular tissue of thoracic aorta （P<0.01）. Conclusion:Shaofu Zhuyutang has a protective effect on vascular endothelial injury in rats with cold coagulation and blood stasis syndrome. The mechanism of action is related to the activation of Nrf2/ARE signaling pathway， which leading to the increased expression of antioxidant enzymes and decreased the expression of adhesion factors.

Role of S-sulfhydration of RhoA kinase in neuroprotection of hydrogen sulfide against hypoxic injury / 中国药理学通报

Aim To investigate the role of S-sulfhydration of RhoA kinase 2 in the neuroprotection of hydrogen sulfide (H2S) against hypoxic injury. Methods Rat hippocampal neurons were primarily cultured and treated with exogenous H2S donor NaHS (50, 100, 200 (xmol • L"1 ) and S-sulfhydration inhibitor DTT (50 (xmol • L"1 during 4 hours of hypoxia and 12 hours of reoxygenation. Cell viability, the lactate dehydrogenase (LDH) activity and neuron-specific enolase (NSE) activity released from injured neuron to culture supernatant, and the proportion of apoptotic cells were measured to assess the neuroprotection of H2S, and the role of S-sulfhydration in the neuroprotection of H2S was preliminarily explored. In addition, the S-sulf- hydrated proteins in neurons were isolated and purified by modified biotin-switch assay. And then, the RhoA kinase 2 (ROCK2) expression and activity, and S-sul- fhydrated ROCK2 were detected to further confirm the role H2S on the S-sulfhydrated ROCK2 by Western blot and assay kits, respectively. Results The decrease of cell viability, and the increase of LDH and NSE released from injured neuron to culture supernatant and cell apoptosis after hypoxia/ reoxygenation ( H/R) were significantly inhibited by 100 and 200 |imol • L"1 NaHS. Compared with the effect of 200 jimol • L"1 NaHS, the neuroprotection of 200 (xmol • L"1 NaHS could be inhibited by co-application with DTT. Furthermore, 100 and 200 (junol • L"1 NaHS could reduce the expression of R0CK2 protein and restrain ROCK2 activity via promoting the S-sulfhydryl modification of ROCK2 protein in hippocampal neurons. Conclusions H2S exerts protective effect on H/R injury of rat hippocampal neurons via down-regulation of ROCK2 expression and inhibition of R0CK2 activity by S-sulfhydration modification.

A new cembranoid diterpene from Olibanum / 中国中药杂志

Five compounds were isolated from the alcohol extract of Olibanum by MCI, silica gel, ODS, and Sephadex LH-20 column chromatographies and preparative high-performance liquid chromatography(HPLC). On the basis of spectral data and literature data, the compounds were identified as:(1S,3R,4S,7R,11S,12R)-1:12,4:7-diepoxisonane-8(19)-ene-3,11-diol(1), boscartin A(2),(+)-resinolin(3),(+)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(4), and acerogenin A(5). Compound 1 is a new compound, and compounds 3-5 were isolated from Olibanum for the first time. The structure of compound 1 was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 were tested for PC12 neurotoxicity, and the results showed that they were both safe compounds.

Analysis of chemical constituents of Ginseng-Douchi compound fermentation products based on UPLC-Q-TOF-MS / 中国中药杂志

In this experiment, ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze and identify chemical constituents of Ginseng-Douchi(GD) compound fermentation, and explore the conversion rules of ginsenosides and soybean isoflavones after compound fermentation. Waters Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was adopted, with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase for gradient elution; electrospray ion source(ESI) was used to collect data in positive and negative ion modes; according to the exact mass number, the secondary spectrum comparison of the database and the existing literature reports, Peakview 2.0/masterview 1.0 software was used to determine the common ion structure formula. Finally, a total of 133 chemical constituents were analyzed and identified from the GD. Ginseng saponins and isoflavone glycosides were significantly converted after fermentation. Among them, peak areas of prototype ginsenosides Rk_3, Rh_1, Rh_2, Rh_3, daidzin, glycitin and genistin decreased significantly; whereas peak areas of se-condary ginsenoside Rb_1, Rb_2, Rk_1, glycitein, genistein and daidzein increased significantly. In this experiment, liquid-mass spectrometry technique was used to investigate the conversion of active ingredients of GD compound fermented products after co-fermentation, so as to provide a scientific basis for elucidating pharmacodynamics material basis and quality control.