Regulation of gluconeogenesis in liver, kidney and intestine by glucagon / 中国药理学通报

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

The gene knockout of ATlaR improves insulin resistance induced by high-fat diet in rats / 中国药理学通报

Aim To explore the role of angiotensin U type 1 a reeeptor ( AT 1 aR ) , an important component of HAS, in obesity-induced insulin resistance.Methods Wild type ( WT) and ATlaR gene knockout (ATlaR ) SD rats were fed with normal diet and 60% high-fat diet for 12 weeks, respectively.After 12 weeks, blood was collected from the abdominal aorta of rats to obtain serum, and the serum insulin level was measured by ELISA.The epididvmal adipose tissue was obtained, and gene expressions of peroxisome pro- liferator-activated receptor -y ( PPAR7) and sterol reg¬ulator}' element binding protein lc (SREBP-lc) in ad¬ipose tissue were detected by RT-PCR method.The protein expressions of insulin signaling pathway and protein kinase C (PKC) in adipose tissue were detec¬ted by Western blot.Results ATI aR knockout signif¬icantly reduced HOMA-IR and improved insulin resist¬ance induced by high-fat diet.In ATlaR rats fed with high-fat, the protein expressions of insulin signa¬ling pathway were much higher than those of WT rats, indicating that ATlaR gene knockout improved the in¬sulin signaling pathway in high-fat diet.In addition, the PKCa, PKCe and PKCr| expressions of ATlaR rats were significantly lower than those of WT rats.And the gene expressions of PPAR-y and SREBP-lc, which promoted adipogenic differentiation, significantly increased in ATlaR rats fed with a high-fat diet, demonstrating that ATlaR knockout promoted adipo¬genic differentiation.Conclusions ATlaR knockout significantly improves high-fat diet induced 1R by en¬hancing protein expressions of insulin signaling path¬way, inhibiting PKC expression and promoting adipo¬genic differentiation.

Effect of panlong needling at Jiaji (EX-B 2) on motor dysfunction in patients with Parkinson's disease of liver and kidney deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the curative effect of panlong needling at Jiaji (EX-B 2) combined with western medication and western medication alone on motor dysfunction in patients with Parkinson's disease (PD) of liver and kidney deficiency.@*METHODS@#A total of 98 patients with PD were randomly divided into an acupuncture and medication group (49 cases, 1 case dropped off) and a western medication group (49 cases,1 case was removed). The patients in the western medication group were given oral of levodopa and benserazide hydrochloride tablets, 125 mg each time, three times a day in the 1st week, and the dose was increased according to the needs of the patients' condition from the 2nd week until 250 mg each time, three times a day, for 16 consecutive weeks. On the basis of the same western medication treatment as the western medication group, panlong needling was applied at Jiaji (EX-B 2) from C2 to L5 in the acupuncture and medication group, once a day, 20 times as a course of treatment, for 4 consecutive courses. The scores of unified Parkinson's disease rating scale (UPDRS-Ⅲ, UPDRS-Ⅳ), TCM symptoms score, and 39-item Parkinson's disease questionnaire (PDQ-39) score were evaluated before treatment, after treatment and during follow-up of 1 month after treatment, respectively. The safety of the two groups was compared.@*RESULTS@#After treatment and during follow-up, except the PDQ-39 score of the western medication group, the scores of UPDRS-Ⅲ, UPDRS-Ⅳ, TCM syndrome and PDQ-39 were lower than those before treatment in the two groups (P<0.05), and the scores of above indexes in the acupuncture and medication group were lower than those of the western medication group (P<0.05). The total incidence of adverse reactions in the acupuncture and medication group was 10.4% (5/48), which was lower than 29.2% (14/48) in the western medication group (P<0.05).@*CONCLUSION@#Panlong needling at Jiaji (EX-B 2) combined with western medication could significantly improve the motor dysfunction and clinical symptoms, improve the quality of life and has high safety, and the efficacy is superior to western medication alone.

Correlation between the number of circulating tumor cells in peripheral blood and clinicopathological features of patients with breast cancer / 肿瘤研究与临床

Objective:To investigate the correlation between the number of circulating tumor cells (CTC) in peripheral blood and clinicopathological features of patients with breast cancer.Methods:The clinical data of 104 breast cancer patients at Guangzhou Panyu Central Hospital between January 2017 and May 2020 were retrospectively analyzed. The number of CTC in peripheral blood, the levels of serum tumor markers [alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA153] were detected. In blood samples, the number of CTC ≥ 2/ml was defined as CTC positive. Immunohistochemistry was used to analyze the protein expression of Ki-67 in tumor tissues. The association of CTC with clinicopathological features, serum tumor markers and Ki-67 protein expression was also analyzed.Results:The CTC positive rate was 80.77% (84/104). There were statistically significant differences in composition of whether there was vascular tumor thrombus (χ 2 = 0.860, P = 0.009), axillary lymph node metastasis (χ 2 = 12.382, P<0.01), N staging ( P = 0.002) and TNM staging (χ 2 = 7.698, P = 0.006) between patients with CTC positive and negative. However, there were no statistically significant differences in composition of age ( t = 0.634, P = 0.528), tumor quadrant (χ 2 = 6.523, P = 0.163), molecular subtyping (χ 2 = 4.164, P = 0.384), histological grade (χ 2 = 1.901, P = 0.387), T staging ( P = 0.099) and whether there was nerve invasion (χ 2 = 0.092, P = 0.761). The levels of serum CEA and CA125 in CTC positive patients were higher than those in CTC negative patients [median ( P25, P75): 2.50 ng/ml (2.21 ng/ml, 2.92 ng/ml) vs. 1.89 ng/ml (1.61 ng/ml, 2.35 ng/ml); 13.81 U/ml (11.79 U/ml, 16.28 U/ml) vs. 11.17 U/ml (8.91 U/ml, 12.80 U/ml); all P < 0.05], and CTC was positively correlated with serum CEA and CA153 levels ( r = 0.520, P<0.01; r = 0.497, P<0.01); CTC was not related to Ki-67 protein expression (χ 2 = 0.512, P = 0.474). Conclusion:The number of CTC in peripheral blood is closely related to clinical staging, lymph node or hematogenous metastasis, tumor markers CEA and CA153 levels of breast cancer. The increased number of CTC may cause tumor progression and metastasis.

Monitoring of birth defects in perinatal infants born during 2015-2019 in Huainan City, Anhui Province / 中国基层医药

Objective:To analyze birth defects in perinatal infants in Huainan city, Anhui province.Methods:The data of perinatal infants with birth defects born during 2015-2019 who were monitored in nine national and provincial birth defect monitoring hospitals in Huainan City were collected. The changes in birth defects, the incidence of birth defects in infants ≥ 28 weeks, urban and rural area distribution of birth defects, type of defects, and the related factors of birth defects during a 5-year study period were analyzed.Results:A total of 90 466 perinatal infants with the incidence of birth defects of 89.87/10 000 were monitored during 2015-2019. The incidence of birth defects in Anhui Province was 139.74/10 000. The proportion of preterm infants < 28 weeks with birth defects among full-term births with birth defects was 30.93% and the proportion increased year by year during 2015-2019, with the proportion of 14.84%, 31.69%, 34.83%, 32.84% and 34.02% respectively. The top five birth defects detected during 2015-2019 were multiple fingers (toes) ( n = 189, 20.89/10 000), cleft lip ( n = 96, 10.61/10 000), external ear deformity ( n = 79, 8.73/10 000), congenital heart disease ( n = 65, 7.19/10 000) and syndactyly ( n = 40, 4.42/10 000). The incidence of birth defects in males and females was 102.77/10 000 and 85.28/10 000, respectively. The incidence of birth defects in urban and rural areas were 107.38/10 000 and 79.60/10 000, respectively. Conclusion:The incidence of birth defects in preterm infants < 28 weeks in Huainan City was lower than that in the whole Anhui Province. The incidence of birth defects in Huainan City differed in different years. The incidence of birth defects in males was higher than that in females. From 2016, the incidence of birth defects in urban area was higher than that in rural area. Birth defects mainly consisted of multiple fingers (toes), external ear deformity, congenital heart disease, cleft lip and syndactyly. The detection rate of birth defects in preterm (< 28 weeks) patients was increased year by year. Early intervention effectively decreased the incidence of birth defects and improved the quality of the population in Huainan City.

Network pharmacology study of Yinqiao Jiedu Soft Capsules in treatment of COVID-19 / 中草药

Objective: To explore the mechanism of Yinqiao Jiedu Soft Capsules in the treatment of coronavirus disease 2019 (COVID-19). Methods: The interactions between 1 418 compounds of Yinqiao Jiedu Soft Capsules and 48 inflammatory target proteins related to COVID-19 were analyzed by molecule docking. The drug-target network was established to clarify the active compounds and potential targets. Results: The network analysis suggested 50 active compounds of Yinqiao Jiedu Soft Capsules, which were mainly flavonoids and triterpenoids, and 37 potential targets, mainly including MTOR, JAK3, ACE, ACE2, PIK3CA, TNF, AKT2, and MAP2K1. The results of molecular docking exhibited that forsythiaside and vitexin 2″-O-rhamnoside had good affinity with SARS-CoV-2 3CL hydrolase, and glycyrrhizic acid had good affinity with ACE2. Conclusion: The molecular mechanism of Yinqiao Jiedu Soft Capsules for COVID-19 may be involved in interfering SARS-CoV-2 replication and regulating the expression of inflammatory signaling pathway and the secretion of inflammatory cytokines.

Effects of salinomycin on proliferation and apoptosis of oral squamous cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of salinomycin on the proliferation and apoptosis of oral squamous carcinoma cells and to further understand the mechanisms of these effects.@*METHODS@#The human oral squamous carcinoma cell line CAL-27 was cultured in different concentrations of salinomycin and cisplatin. After co-culture with 0, 1, 2, 4, 8, 16 and 32 μmol/L salinomycin or 0, 1.25, 2.5, 5, 10, 20, 40 and 80 μmol/L cisplatin for 24 hours and 48 hours, the proliferation of oral squamous carcinoma cells were detected by cell counting kit-8(CCK-8) assay. After being exposed to 0, 2, 4, 8 μmol/L salinomycin and 0, 5, 10, 20 μmol/L cisplatin for 48 hours, the cell cycle of oral squamous carcinoma cells was detected by flow cytometry assay, and Western blot analysis was performed to analyze the expressions of cysteine-containing aspartate-specific proteases-3(Caspase-3), cysteine-containing aspartate-specific proteases-9(Caspase-9), poly ADP-ribose polymerase (PARP), protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt) protein in oral squamous carcinoma cells.@*RESULTS@#Both salinomycin and cisplatin significantly inhibited the proliferation of oral squamous cell carcinoma CAL-27 cells in a time- and dose-dependent manner. However, compared with the first-line chemotherapeutic drug cisplatin, salinomycin showed stronger anti-proliferation activity in oral squamous carcinoma cells than cisp-latin (P < 0.001). After being exposed to 8 μmol/L salinomycin, CAL-27 cells exhibited markedly higher proportion in quiescent/ first gap phases (40.40%±1.99% vs. 64.46%±0.90%, P < 0.05), and had a significantly lower proportion in synthesis phases and second gap / mitosis phases (24.32%±2.30% vs. 18.73%±0.61%, P < 0.05; 35.01%±1.24% vs. 16.54%±1.31%, P < 0.05) compared with the dimethyl sulfoxide control group; moreover cisplatin didn't show cell-cycle specific effect on CAL-27. Western blot proved that salinomycin could up-regulate the expressions of Caspase-3 and Caspase-9 protein in oral squamous cell carcinoma CAL-27 cells (P < 0.05). At the same time, the levels of PARP, Akt and p-Akt protein were down-regulated (P < 0.05).@*CONCLUSION@#Compared with cisplatin, salinomycin has a better inhibitory effect on the proliferation of oral squamous carcinoma cells and blocks the cell cycle process at the quiescent / first gap phase. At the same time, salinomycin could trigger apoptosis of oral squamous carcinoma cells and the mechanism is associated with the Akt/p-Akt signaling pathway.

Rules of Meridians and Acupoints Selection in Treatment of Parkinson's Disease Based on Data Mining Techniques / 中国结合医学杂志

OBJECTIVE@#To help selecting appropriate meridians and acupoints in clinical practice and experimental study for Parkinson's disease (PD), the rules of meridians and acupoints selection of acupuncture and moxibustion were analyzed in domestic and foreign clinical treatment for PD based on data mining techniques.@*METHODS@#Literature about PD treated by acupuncture and moxibustion in China and abroad was searched and selected from China National Knowledge Infrastructure and MEDLINE. Then the data from all eligible articles were extracted to establish the database of acupuncture-moxibustion for PD. The association rules of data mining techniques were used to analyze the rules of meridians and acupoints selection.@*RESULTS@#Totally, 168 eligible articles were included and 184 acupoints were applied. The total frequency of acupoints application was 1,090 times. Those acupoints were mainly distributed in head and neck and extremities. Among all, Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor Controlled Zone were the top five acupoints that had been used. Superior-inferior acupoints matching was utilized the most. As to involved meridians, Du Meridian, Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver) Meridian were the most popular meridians.@*CONCLUSIONS@#The application of meridians and acupoints for PD treatment lay emphasis on the acupoints on the head, attach importance to extinguishing Gan wind, tonifying qi and blood, and nourishing sinews, and make good use of superior-inferior acupoints matching.

Molecular Mechanism of Sanjie Zhentong Capsule in Treatment of Endometriosis, Adenomyosis, Secondary Dysmenorrhea / 中国实验方剂学杂志

Objective: To analyze the pharmacological basis and molecular mechanism of Sanjie Zhentong capsule in the treatment of endometriosis, adenomyosis, secondary dysmenorrhea. Method: The 6 compounds of Sanjie Zhentong capsule showed stronger interactions with 87 proteins relating to endometriosis, adenomyosis, and secondary dysmenorrhea in molecular docking. Then the drug-target network was selected, and the network features were analyzed. Result: The molecular docking and network characteristics revealed 5 main active molecules and 23 potential targets of Sanjie Zhentong capsule. Conclusion: The main active ingredients of Sanjie Zhentong capsule have a trong inhibition effect on endometrial angiogenesis and blood circulation, uterine smooth muscle contraction, immune inflammatory reaction and estrogen secretion by acting on the targets of inflammation, cell invasion, metastasis, coagulation system, smooth muscle contraction and neurohormone regulation, so as to treat endometriosis, adenomyosis and secondary dysmenorrhea.

Effects and mechanism of injection of glutamate into hypothalamic paraventricular nucleus on visceral pain in chronic visceral hypersensitivity rats / 中华行为医学与脑科学杂志

Objective@#To investigate the effects of glutamate (Glu) injected into hypothalamic paraventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possible mechanism.@*Methods@#Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th, 10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group), CVH + injection of saline into PVN group (NS group), CVH+ injection of Glu into PVN (3, 6, and 12 μg Glu, namely G3, G6, and G12, respectively), 6 rats in each group, and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold, abdominal withdrawal reflex (AWR) score, and abdominal external oblique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL.@*Results@#Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups increased, and the AWR scores and EMG amplitudes decreased. The differences were statistically significant(Pain threshold: t=7.65, 16.31, 24.78, both P<0.05; AWR scores: t=-2.98, -4.77, -7.29, both P<0.05; EMG amplitudes: t=-3.06, -5.75, -8.92, both P<0.05). Compared with the Sham group, the expression of AVP in PVN of the CVH group and NS group decreased ((42.63±5.20) %, (18.67±2.94) %, (17.53±2.47) %; t=6.95, t=7.56, both P<0.05). The expression of AVP was increased after different doses of Glu into PVN, and the AVP level in G12 group ((18.15±6.49)%) was higher than that of NS group, the difference was statistically significant (t=-4.21, P<0.05). Compared with the Sham group, the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65.48±1.68) %, (18.39±1.67) %, (17.69±1.68) %; t=34.35, t=34.80, both P<0.05). The expression of PCNA was increased after different doses of Glu injected into PVN, and the PCNA level in G12 group ((59.91±5.63)%) was higher than that of NS group, the difference was statistically significant (t=-12.44, P<0.05). Compared with the Sham group, the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23.38±11.40)%, (83.79±3.57)%, (80.91±2.47)%; t=-8.77, t=-8.54, both P<0.05). The expression of apoptotic cells was decreased after different doses of Glu into PVN, and the G12 group was ((18.15±6.49) %). Compared with NS group, the difference was statistically significant (t=15.65, P<0.05).@*Conclusion@#Injection of Glu into hypothalamic PVN can alleviate the visceral pain behaviors in CVH rats, and its mechanism may be related to arginine vasopressin.

Effects and mechanism of injection of glutamate into hypothalamic paraventricular nucleus on viscer-al pain in chronic visceral hypersensitivity rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of glutamate (Glu) injected into hypothalamic pa-raventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possi-ble mechanism. Methods Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th,10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group),CVH + injection of saline into PVN group (NS group),CVH+ injection of Glu into PVN (3,6,and 12 μg Glu,namely G3,G6,and G12,respectively),6 rats in each group,and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold,abdominal withdrawal reflex (AWR) score,and abdominal external ob-lique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL. Results Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups in-creased,and the AWR scores and EMG amplitudes decreased. The differences were statistically significant (Pain threshold:t=7. 65,16. 31,24. 78,both P<0. 05;AWR scores:t=-2. 98,-4. 77,-7. 29,both P<0. 05;EMG amplitudes:t=-3. 06,-5. 75,-8. 92,both P<0. 05). Compared with the Sham group,the expression of AVP in PVN of the CVH group and NS group decreased ((42. 63±5. 20) %,(18. 67±2. 94) %,(17. 53± 2. 47) %; t=6. 95,t=7. 56,both P<0. 05). The expression of AVP was increased after different doses of Glu into PVN,and the AVP level in G12 group ((18. 15±6. 49)%) was higher than that of NS group,the difference was statistically significant (t=-4. 21,P<0. 05). Compared with the Sham group,the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65. 48±1. 68) %,(18. 39± 1. 67) %,(17. 69±1. 68) %;t=34. 35,t=34. 80,both P<0. 05). The expression of PCNA was increased after different doses of Glu injected into PVN,and the PCNA level in G12 group ((59. 91±5. 63)%) was higher than that of NS group,the difference was statistically significant (t=-12. 44,P<0. 05). Compared with the Sham group,the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23. 38±11. 40)%,(83. 79± 3. 57)%,(80. 91± 2. 47)%;t=-8. 77,t=-8. 54,both P<0. 05). The expression of apoptotic cells was decreased after different doses of Glu into PVN,and the G12 group was ((18. 15±6. 49) %). Compared with NS group,the difference was statistically significant ( t=15. 65,P<0. 05). Conclusion Injection of Glu into hypothalamic PVN can alleviate the visceral pain be-haviors in CVH rats,and its mechanism may be related to arginine vasopressin.

Role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock waves therapy / 中华心血管病杂志

Objective@#To investigate the role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock therapy.@*Methods@#Adult male Sprague Dawley (SD) rats weighing 220-250 g were used to establish a heart failure model by ligation of the left anterior descending coronary artery. Rat models were defined by echocardiographic assessment at 4 weeks post operation and heart failure rats were randomly divided into 4 groups,namely heart failure group (HF group, 9 cases),heart failure+cardiac shock waves therapy group (HF+CSWT group, 9 cases),heart failure+inhibitor(HF+LY294002 group, 9 cases),heart failure+cardiac shock waves therapy group+inhibitor (HF+CSWT+LY294002 group, 9 cases),and another 9 sham-operated SD rats served as control group (sham group, 9 cases). At 8 weeks postoperation, echocardiography was used to evaluate cardiac function in each group,myocardial infarct size was measured by TTC staining,the apoptotic index of rats cardiomyocytes were detected by TUNEL method,the myocardial mRNA expression of apoptosis-related factor was detected by real-time quantitative PCR, the protein expression levels of PI3K/Akt signaling pathway and apoptosis-related pathways were detected by Western blot.@*Results@#(1) Eight weeks after operation, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly lower in HF+CSWT group than in HF group (all P<0.05), left ventricular ejection fraction (LVEF) and left ventricular shortening rate (LVFS) were significantly higher in HF+CSWT group than in HF group (all P<0.05),LVEF was significantly lower in the HF+ CSWT+ LY294002 group than in HF+ CSWT group (P<0.05). (2) Myocardial infarct size was significantly lower in the HF+ CSWT group than in HF group ((5.57 ± 0.51)% vs. (25.56 ± 0.56)%, P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in HF+CSWT group ((12.90±2.34)% vs. (5.57±0.51)%,P<0.05). (3) The cardiomyocyte apoptotic index was significantly lower in the HF+CSWT group than in the HF group ((30.25±6.12)% vs. (53.85±9.89)%,P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in the HF+CSWT group ((46.12±3.42)% vs.(30.25±6.12)%,P<0.05). (4) The myocardial mRNA expression of Bcl-2 was significantly higher, while myocardial mRNA Bax and Caspase-3 expression were significantly lower in HF+CSWT group than in HF group and HF+CSWT+LY294002 group (all P<0.05). (5) The expression levels of p-Akt, Bcl-2 and pro-Caspase-3 in myocardial tissue were significantly higher in the HF+CSWT group than in the HF group and HF+CSWT+LY294002 group (all P<0.05), which were significantly lower in the HF+LY294002 group than in the HF and HF+CSWT+LY294002 groups (all P<0.05). Myocardial Bax protein expression was significantly lower in the HF+CSWT group than in the HF group and the HF+CSWT+LY294002 group (all P<0.05), which was significantly higher in the HF+LY294002 group than in the HF group (P<0.05).@*Conclusion@#CSWT improves cardiac function and inhibits cardiomyocyte apoptosis through PI3K/Akt signaling pathways in this rat HF model.

Clinical efficacy of nasal high-frequency ventilation in treatment of neonatal respiratory distress syndrome: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the clinical efficacy of nasal high-frequency ventilation (nHFV) in the treatment of neonatal respiratory distress syndrome (NRDS).@*METHODS@#A literature search was performed in PubMed, Cochrane Library, EMBase (Ovid), Chinese Biomedical Literature Database, Chinese Journal Full-text Database, Wanfang Data, and Weipu Data to collect the randomized controlled trials (RCTs) that compared the clinical efficacy of nHFV and nasal continuous positive airway pressure (nCPAP) in the treatment of NRDS. A Meta analysis was performed on the included RCTs using Rev Man 5.3 software after data extraction and quality evaluation by Cochrane 5.1.0.@*RESULTS@#A total of 4 RCTs involving 218 patients were included. The Meta analysis showed that compared with the nCPAP group, the nHFV group had a significantly better treatment outcome (RR=1.73, 95%CI: 1.39-2.15, P<0.00001). There were no significant differences in the incidence rates of intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis, pneumothorax and retinopathy of prematurity.@*CONCLUSIONS@#Compared with nCPAP, nHFV has better clinical efficacy in the treatment of NRDS, without increasing the risk of related complications.

Effect and Mechanism of Glutamic Acid Injection Into Cerebellar Fastigial Nucleus on Chronic Visceral Hypersensitivity in Rats / 胃肠病学

Background:Cerebellar fastigial nucleus (FN)is involved in regulation of visceral activities such as cardiovascular, ingestion,respiratory,and acute gastric mucosal injury,yet it is unclear whether it participates in the regulation of visceral hypersensitivity and what is the possible mechanism. Aims:To investigate the effect and possible mechanism of glutamic acid (Glu ) injection into cerebellar FN on chronic visceral hypersensitivity in rats. Methods: Chronic visceral hypersensitivity rat model was established by neonatal colorectal distension (CRD). After 8 weeks,the rats were divided into CRD group,solvent group (0. 2 μL 0. 9% NaCl solution injection into cerebellar FN),high-,medium-,low-dose Glu groups (12,6,3 μg Glu injection into cerebellar FN,respectively),3-MPA +Glu group (12 μg Glu injection after glutamate decarboxylase inhibitor 3-MPA injection into cerebellar FN),Bic + Glu group (12 μg Glu injection into cerebellar FN after GABAAreceptor blocker Bic injection into lateral hypothalamic area). Pain threshold,abdominal withdrawal reflex (AWR)score and abdominal external oblique muscle electromyography (EMG)were used to detect visceral sensitivity,and malondialdehyde (MDA)content and superoxide dismutase (SOD)activity were measured. Results:Chronic visceral hypersensitivity rat model was successfully established. Compared with CRD group,pain threshold was significantly increased (P＜0. 05),AWR score,EMG amplitude,MDA content were significantly decreased (P＜0. 05 ),and SOD activity was significantly increased in a dose-dependent manner in Glu group (P ＜0. 05 ). Compared with 12 μg Glu group,pain threshold was significantly decreased (P＜0. 05),AWR score,EMG amplitude, MDA content were significantly increased (P ＜0. 05),and SOD activity was significantly decreased in 3-MPA +Glu group,Bic+Glu group (P＜0. 05). Conclusions:Glu injection into cerebellar FN can significantly reduce the visceral sensitivity in rats. The mechanism may be that Glu in cerebellar FN produces GABA via glutamate decarboxylase,and then binding GABAAreceptor in lateral hypothalamic area,resulting in increased intestinal mucosal antioxidant capacity, thereby reducing visceral hypersensitivity.

Identification of a Novel Homozygous Splice-Site Mutation in that Causes Progressive Myoclonus Epilepsy with or without Renal Failure / 中华医学杂志(英文版)

<p><b>Background</b>Progressive myoclonus epilepsies (PMEs) comprise a group of rare genetic disorders characterized by action myoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome (EPM4) family and summarize the clinical and genetic characteristics of all reported EPM4 patients.</p><p><b>Methods</b>In the present study, targeted next-generation sequencing (NGS) was applied to screen causative genes in a Chinese PME family. The candidate variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband's muscle. Moreover, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed.</p><p><b>Results</b>The gene analysis revealed a novel homozygous splicing mutation (c.995-1G>A) of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4.</p><p><b>Conclusions</b>These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.</p>

In vivo study of 3D printed porous tantalum implant on osseointegration / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This work aims to investigate the effect of porous tantalum and porous titanium on osseointegration.</p><p><b>METHODS</b>Two kinds of porous materials with same microporous parameters, namely, porous tantalum and porous titanium, were fabricated by computer-aided design (CAD) modeling and 3D printing technology. A defect model was established in 24 New Zealand white rabbits in the bilateral femoral lateral malleolus at the left and right side of each animal. Then, animals were randomly divided into two groups, and bone defects were repaired by porous tantalum and porous titanium (experimental and control groups, respectively). Animals were sacrificed at two, four, and eight weeks after implantation. Gross observation and methylene blue-acid fuchsin staining were used to observe osseointegration of the implant and bone interface, and the osseointegration strength of implant bone interface was tested by push-out test.</p><p><b>RESULTS</b>At two, four, and eight weeks after operation, the new bone tissue in the two groups increased gradually, and new bone trabecula appeared and grew into the pores of the materials. No significant difference (P>0.05) in osteogenesis and the strength of implant bone tissue interface between the two groups was observed.</p><p><b>CONCLUSIONS</b>3D
printed porous tantalum implants, which exhibit comparable osseointegration capabilities to porous titanium implants, can form an early biological combination with bone tissue.</p>

A new aurone with anti-inflammatory activity from Cleistocalyx operculatus flower buds / 中国中药杂志

A new compound(Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone was isolated from Cleistocalyx operculatus flower buds. Its structure was identified by spectroscopic data including MS, ¹H-NMR, ¹³C-NMR HSQC and HMBC. A known compound, 2',4'-dihydroxy-6'-methoxy-3'5'-dimethylchalcone (DMC), was also isolated and identified,and used as material to synthesize (Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone.Anti-inflammatory activities of the two compounds were tested . The results showed that (Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone possesses much stronger PGE₂ inhibitory activity (IC₅₀ 6.12 nmol·L⁻¹) than the positive control ibuprofen （68.66 nmol·L⁻¹）.

Prognostic Value of a Change in Troponin-Ⅰ Levels in Patients with Sepsis-associated Myocardial Dysfunction / 中国医科大学学报

Objective To investigate the expression of cardiac troponin-Ⅰ (cTnⅠ) levels in patients diagnosed with sepsis-associated myocardial dysfunction and explore the relationship between cTn Ⅰ and cardiac systolic and diastolic function.Additionally,we evaluated the prognostic value of cTn Ⅰ as a valuable biomarker.Methods We admitted 65 patients with sepsis.Using echocardiography,the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e') and the left ventricular ejection fraction (LVEF) were measured as an evaluation index of left ventricular diastolic and systolic function,respectively.Patients were divided into a cardiac dysfunction and a normal cardiac function group.The cTn Ⅰ level was measured and compared between the two groups,and we determined the correlation between cTn Ⅰ levels and cardiac diastolic and systolic function.Based on assessment of 28-day mortality,cases were divided into a survivor and a death group.A receiver operating characteristic curve was constructed to predict the prognostic value of cTn Ⅰ.Results The cTn Ⅰ level in the cardiac dysfunction group was significantly higher than that observed in the normal cardiac function group (P ＜ 0.05) and showed a positive correlation with E/e'(r =0.421,P =0.008).However,there was no correlation noted between the cTn Ⅰ level and LVEF (P ＞ 0.05).Compared to the survivor group,the level of cTn]Ⅰ was significantly higher in the death group (P ＜ 0.05).The prognostic value of cTn Ⅰ area under the curve was 0.892,with a cut-off value of 0.82 ng/mL (sensitivity =88.0％ and specificity =82.5％).Conclusion The cTn Ⅰ level is noted to be significantly elevated in patients with sepsis-associated cardiac dysfunction and shows a positive correlation with left ventricular diastolic function.A cTn Ⅰ level ≥ 0.82 ng/mL can be used as a valuable predictor of mortality in patients with sepsis.

Genetic polymorphisms of 19 STR loci in han popu-lation from Hainan and its application in paternity testing / 中国法医学杂志

Objective To construct a database for the genetic polymorphism of 19 STR loci in Han population from Hainan province. To investigate the application of 19 STR loci in the paternity testing. Methods The genotypes of 462 unrelated individuals in Hainan were detected with GoldeneyeTM 20A PCR Amplification Kit. 19-STR database was acquired, analyzed and evaluated in 283 paternity testing cases. Results No deviations of allele frequency from Hardy-Weinberg equilibrium expectations were found for Chi-square test (P>0.05). Observed heterozygosity (Hobs) varied between 0.603 and 0.914, total discrimination power (TDP) of 19 STR loci was more than 0.999999999999999, cumulative probability of exclusion (CPE) for triplet cases was 0.999999994. In all 283 paternity testing cases, triplets and duos were 170 and 113 respectively; there were 36 (12.7%) excluded cases comparing to 247 confirmed cases (87.3%). 14 mutation events were observed, and all were one-step mutation. Conclusion 14 out of 19 loci showed highly polymorphic in Han population from Hainan, and 19 STR system has high cumulative probability of exclusion and can meet the needs of paternity test of the local region. But mutation should be paid special attention to.

Significance of Troponin-I in patients with septic shock and left ventricular diastolic dysfunction / 实用医学杂志

Objective To investigatethe clinical value of troponin-I(cTnI)in patientswith septic shocka-nd left ventricular diastolic dysfunction. Methods As a retrospective analysis ,38 patients with left ventricular di-astolic dysfunction and septic shock(Sa group),as well as 20 patients with normal cardiac function(Sn group) were enrolled in this study. Moreover ,20 patients with left ventricular diastolic dysfunction and without septic shock were used as control group(Ca group). The ratio of early diastolic mitral inflow velocity to early diastolic mi-tral annulus velocity(E/e′)was measured as the evaluation index of left ventricular diastolicfunction by echocar-diography within 72 hours after admission to ICU. Level of cTnI was detected in all cases and the relationship was evaluated by E/e′. Receiver operating characteristic curve(ROC)was constructed to indicate the predictable value of left ventricular diastolic dysfunction in patients with septic shock. Results The level of cTnI was significantly elevated in both Sa group and Sn group(P<0.05),while the level of cTnI and E/e′in Sa group were significantly higher than those in Sn group(P < 0.05). cTnI was positively correlated with E/e′(r = 0.367 ,P = 0.004). The area under the curve(AUC)of cTnI was 0.834,with the cut-off value of 0.49 ng/mL(sensibility=77.6,specificity=80.7). Conclusion The level of cTnI was significantly higher in patients with septic shock. cTnI was significantly correlated to left ventricular diastolic dysfunction in patients with septic shock. cTnI ≥ 0.49 ng/mL could be an available predictor for left ventricular diastolic dysfunction in patients with septic shock.