Objective To investigate the short-term therapeutic effect of liraglutide injection combined with insulin pump subcutaneous infusion of insulin in the treatment of early-onset obesity.Methods 100 patients with diabetes mellitus treated with endocrine specialist outpatients from May 2015 to August 2016 in our hospital were selected and randomly divided into three groups,insulin+liraglutide injection 1.2 mg/d group(treatment group 1),insulin+metformin 0.5 tid group(treatment group 2)and insulin intensive group(control group).The control group of 20 cases,the remaining 40 cases each group.Each patient was treated with their own treatment regimen.Target blood glucose: fasting blood glucose≤7.0mmol/L,2h postprandial blood glucose≤10mmol/L that is compliance,blood glucose≤4.4mmol/L that low,blood glucose≤3.9mmol/L that low blood sugar.Two groups of patients adhere to three months of treatment.At the time of admission,after 2 weeks of treatment and 6 months of treatment,venous blood was taken for biochemical examination.The corresponding biochemical indicators were compared and the therapeutic effects of the two regimens were compared.Results There were significant differences in the levels of fasting glucagon,fasting C-peptide and body mass index between the two groups after three weeks of treatment and three months after treatment(P<0.05).The total amount of insulin,the time of reaching the standard and the frequency of hypoglycemia of three groups were compared,the difference was statistically significant(P<0.05).Conclusion Using three kinds of treatment for the treatment of elderly obese diabetesmellitus have a significant effect.However,the treatment regimen of insulin+liraglutideinjection 1.2 mg/d is effective in the control of diabetes and the total insulin dosage,as well as the number of hypoglycemia occurred,are better than the other two groups of treatment.

Objective To study the influence of continuous blood purification(CBP)on the intra-abdomi-nal pressure (IAP ) and the gastrointestinal dysfunction of intra -abdominal hypertension (IAH ).Methods 80 patients with IAH were selected and divided into observation group and control group(n=40)according to random number table method.The observation group was given 3d CBP therapy.The control group was given conventional treatment.The mean arterial pressure (MAP ),IAP and abdominal perfusion pressure (APP ) were detected.The number of gastrointestinal symptoms was observed,sequential organ failure score(SOFA score)was used to assess the organ function of the two groups before and after treatment.Results The MAP,IAP,APP,SOFA score of the two groups before treatment had no statistically significant differences(P>0.05).The MAP of the two groups after treat-ment[(88.46 ±8.93)mmHg vs.(87.76 ±8.04)mmHg]had no statistically significant difference(P>0.05).The IAP[(9.02 ±1.06)mmHg]and SOFA score[(1.32 ±0.45)]of the observation group after treatment were signifi-cantly lower,the APP [(85.34 ±7.59)mmHg]was obviously higher than before treatment and the control group [(19.54 ±4.23)mmHg,(5.24 ±2.05)points,(70.76 ±6.43)mmHg],the differences were statistically significant (t=3.575,2.855,3.274,3.563,3.114,3.782,all P<0.05).Before treatment,the number of the gastrointestinal symptoms of the two groups[(44.56 ±8.53)times vs.(45.32 ±8.21)times]had no statistically significant difference (P>0.05).The number of gastrointestinal symptoms of the observation group after treatment [(6.54 ±2.24)times] was obviously lower than before treatment and the control group [(15.45 ±4.43)times],the difference was statisti-cally significant(t =3.022,P<0.05 ).The 30 d and 60 d survival rates of the observation group were 87.5%(35/40)and 65%(26/40),which of the control group were 80.0%(32/40)and 55%(22/40),although which of the observation group were higher than the control group,but there were no statistically significant differences(P>0.05 ).Conclusion CBP could significantly reduce the IPA of the patients with IAH,raise the APP,improve gastro-intestinal perfusion,reduce gastrointestinal symptoms,has positive significance to improve the gastrointestinal dysfunction.

Objective To observe the therapeutic effects of the drugs alternation multiple stages and long term therapy in elderly patients with recurrent urinary tract infection.Methods The patients were divided into elderly group (age≥65 years,n=30) and non-elderly group (n=48).The multiple effective antibiotics were selected for alternate use.The treatment included four periods as follows:(1)Treatment period:the regular dose of antibiotic was maintained until the urine routine test result became normal;(2)Consolidation period:the dosage of antibiotic was reduced;(3)Maintenance period:the dosage of antibiotic was reduced to once every night and the treatment should be kept for three months;(4)Observation period:the patients were observed for six months after withdrawal of antibiotics.During the treatment,if the urine routine test became abnormal repeatedly,the patient should return to the previous treatment period.During the treatment and consolidation period,each medication should be applied for one week alternatively.Results Among 78 patients,69 cases (88.5%) were cured,7 cases (8.9%) were effective,and two cases (2.56%) were invalid.There were 28 cured cases,1 effective case and 1 invalid case in elderly group.The corresponding data were 41,6 and 1 in non-elderly group,respectively.There was no difference in cure rate between the two groups (F= 0.469).Compared with non-elderly group,the overall treatment time [(54.8± 16.2)weeks vs.(44.5± 13.7) weeks,t= 2.8467,P＜0.01],treatment period [( 34.3± 15.2) weeks vs.(26.2±14.8) weeks,t=2.2081,P＜0.05] and consolidation period [(5.7±2.6) weeks vs.(4.1±0.2) weeks,t=3.9369,P＜0.01] were all prolonged in elderly group.But there was no difference in maintenance period [(14.8±4.6) weeks vs.(14.2±3.1) weeks,t=0.6480,P＞0.05].There were no markedly changes in blood routine,liver and kidney function during the course of treatment.Conclusions For the elderly patients with recurrent urinary tract infection,the drugs alternation,multiple stages and long-term treatment has a high cure rate and no adverse effect on blood routine,liver and renal function.

With the development of modern technology and clinical practice,the classic randomized controlled trial nowadays cannot meet the researchers' needs for evidence with more reliable external validity,especially in the field of TCM.Meanwhile,real-world study (RWS) has been attracting more attention and at the forefront of clinical research all over the world for providing evidence in conformity with the real world condition.In this paper,we firstly described the basic concept of RWS,and then found that it was characterized by large representative samples,loose inclusion or exclusion criteria,allocation of interventions according to patients conditions and willingness,long-term follow-up,and clinically relevant endpoints.By analyzing the existing examples of RWS,we noted and discussed the promising future of RWS in TCM clinical research.Finally,we hope this paper will provide some inspiration for TCM researchers.

OBJECTIVETo study the role of integrin-linked kinase (ILK) on the proliferation and differentiation of human fibroblast in hypertrophic scar and its effect on the scar formation.

METHODSThe human scar fibroblasts were isolated and cultured in vitro. The cells were divided into 4 groups. (1) control group: only contains DMEM; (2) jetPRIME group: DMEM with 200 microl jetPRIME buffer and 4 microl jetPRIME; (3) ILK siRNA group: DMEM and ILK siRNA; (4) ILK cDNA group: DMEM and ILK cDNA. The cell proliferation was detected by XTT assay and the mRNA and protein expressions of ILK and alpha-SMA were detected by Real-time qPCR and Western blot.

RESULTS(1) XTT results showed that the cellular proliferation level after 48 h in four groups were 0.820 +/- 0.065, 0.873 +/- 0.041, 0.554 +/- 0.013 and 1.296 +/- 0.094, respectively. The cellular proliferation curve showed that the cellular proliferation level was very flat in ILK siRNA group while the cellular proliferation level gradually increased from 12 h. 48 h after transfection, the cellular proliferation level in ILK siRNA group was significant lower than those in other groups (P value were 0.021, 0.034, 0), while the cellular proliferation level in ILK cDNA group was the highest among all 4 groups (P value were 0.017, 0.009, 0). (2) The Real-time qPCR showed that the expressions of ILK mRNA and alpha-SMA mRNA were 0.693 +/- 0.412 and 0.422 +/- 0.037 in control group, were 0.621 +/- 0.183 and 0.388 +/- 0.005 in jetPRIME group, were 0.052 +/- 0.019 and 0.073 +/- 0.023 in ILK siRNA group, were 240.193 +/- 35.170 and 138.056 +/- 24.060 in ILK cDNA group. The expressions of ILK mRNA and alpha-SMA mRNA in ILK siRNA group were significantly lower than those in other three groups (P < 0.05). And the expressions of ILK mRNA and alpha-SMA mRNA in ILK cDNA group were significantly higher than those in other three groups (P < 0.05). (3) The Western blot also showed that the expression of ILK and alpha-SMA proteins were decreased in ILK siRNA group and increased in ILK cDNA group.

CONCLUSIONILK may promote the proliferation and differentiation of human scar fibroblast. It may play an important role in scar formation and contracture.

Actins ; metabolism ; Adolescent ; Adult ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Female ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Male ; Middle Aged ; Protein-Serine-Threonine Kinases ; pharmacology ; RNA, Messenger ; genetics ; Transfection ; Young Adult

Objective:To study the safety and feasibility of early enteral feeding during therapeutic hypothermia guided by intestinal ultrasound in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:From January 2019 to December 2021, neonates with HIE who received therapeutic hypothermia in the neonatology department of our hospital were retrospectively selected. They were assigned into the ultrasound-guided observation group (admitted from May 2020 to December 2021) and the control group (admitted from January 2019 to April 2020). In the ultrasound-guided observation group, intestinal ultrasound was performed during therapeutic hypothermia. Based on clinical manifestations and ultrasound results, a small amount of enteral feeding [20 ml/(kg·d)] was initiated and gradually increased to total enteral feeding after rewarming. In the control group, 5 ml (once every 3 h) of glucose and sodium chloride solution was given during 72 h of therapeutic hypothermia. After rewarming, enteral feeding was started and gradually increased to total enteral feeding without intestinal ultrasound. The time to start enteral feeding, the time to achieve total enteral feeding, the incidences of feeding intolerance, necrotizing enterocolitis (NEC) and late-onset sepsis were compared between the two groups.Results:A total of 17 cases were in the ultrasound-guided observation group and 18 cases in the control group. The median time to start enteral feeding and to achieve total enteral feeding in the ultrasound-guided observation group were earlier than the control group [36.0 (33.5, 39.0) h vs. 77.0 (74.0, 79.3) h, 6.0 (5.5, 6.5) d vs. 8.0 (7.0, 9.0) d, P<0.001]. No significant difference existed in the incidence of feeding intolerance between the two groups. Neither groups had NEC or late-onset sepsis. Conclusions:Early enteral feeding during therapeutic hypothermia in neonates with HIE is safe and feasible. Intestinal ultrasound helps implementing feeding plan and achieving early total enteral feeding.

Objective: To evaluate the effect of traditional Chinese medicine (TCM) on anthracycline-induced car-diotoxicity (AIC) in animal models. Methods: Separate systematic searches for preclinical studies were performed in the PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Chinese Sci-entific Journal Database, and Wanfang Data from inception to August 2019. The primary outcomes were echocardiography, serum assays for myocardial enzymograms, histological assessments, and electro-cardiograms. The secondary outcomes mainly included body weight and safety evaluations. The protocol is registered on PROSPERO (CRD42019145819). RevMan (V.5.3) was used for meta-analysis. Results: We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models. All the included studies reported that, compared with animal model without any intervention, TCM significantly improved ventricular function, cardiac biomarkers, electrocardio-graph results, and cardiac fibrosis. Improved survival rates and body mass indices were also observed with TCM. We further pooled the available data from four studies (63 animals) for the meta-analysis and the results showed that, compared with models without any intervention, TCM significantly increased the ejection fraction by 14.13％ (95％ CI, 9.96-18.29) and fraction shortening by 8.66％ (95％ CI, 6.05-11.26). Creatine kinase-MB (SMD = -2.49, 95％ CI: -3.12 to -1.85) and lactate dehydrogenase (SMD =-2.78, 95％ CI:-3.45 to-2.12) were also significantly decreased by TCM. Conclusions: TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice. Additionally, the systematic review and meta-analysis of an-imal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.

Filamentous fungi are important industrial microorganisms that play important roles in the production of bio-based products such as organic acids, proteins and secondary metabolites. The development of metabolic engineering and its enabling techniques have greatly promoted the design, construction and application of filamentous fungal cell factories. This article systematically reviews the development of filamentous fungal cell factories constructed through metabolic engineering, and discusses the challenges and future perspectives for systems metabolic engineering of filamentous fungi.
Fungi/genetics* ; Metabolic Engineering

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone