SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective: To investigate the early diagnosis and treatment for burn complicated with severe paroxysmal sympathetic hyperactivity (PSH). Methods: Medical records of patients with burn complicated with severe PSH, admitted to our department from April 2016 to March 2019 and meeting the inclusion criteria were analyzed retrospectively. There were 4 males and 1 female, aged 17 months to 39 years, with an average of (21±16) years. During occurrence of PSH, the vital signs of patients were routinely monitored and oxygen were given. Other treatment included central venous catheterization and infusion of electrolyte solution, infusion of plasma according to patients′ condition, use of opioid analgesics and benzodiazepine sedatives, physical cooling and drug cooling, and establishment or maintenance of artificial airway and use of ventilator. Heart rate was controlled below 120 beats per minute in adults and 140 beats per minute in children with comprehensive treatment dominated by analgesia and sedation. Besides, single or multiple vasoactive agents, even in large doses were used to maintain normal blood pressure of patients. The occurrence characteristics, time, and treatment outcome of PSH were analyzed. Results: PSH happened rapidly, with a sharp increase in several minutes to dozens of minutes. Five patients were with symptoms such as high body temperature, shortness of breath, very fast heart rate, normal or elevated systolic blood pressure, hyperhidrosis, and dystonia at the onset. The symptoms occurred simultaneously or successively. According to the Clinical Feature Scale, the above-mentioned 6 indexes achieved the highest score of 3 points except of systolic blood pressure. Four patients showed dilated pupils and impaired consciousness. Among the patients, PSH occurred in the acute exudation stage in 3 patients, in the fluid reabsorption stage in 1 patient, and in the late repair stage in 1 patient. PSH of patients lasted for 3 hours to 12 days. The symptoms of 4 patients were effectively controlled, and 1 patient died of deterioration. No PSH occurred in the cured patients during follow-up of 3 to 14 months. Conclusions Burn complicated with PSH can occur at any time before wound repair and in patients with different injury conditions. The causes of PSH include sudden burn, persistent pain, fright and fear, strange environment, low blood volume, and other adverse stimuli, and PSH is more likely to occur in children with underdeveloped brain function. Intravenous infusion of analgesics sedatives, physical therapy and medication to lower body temperature, stabilizing blood pressure and respiration are effective measures to treat PSH. PSH should be distinguished from the common complications of burns, such as sepsis, cerebral edema, hyperpyretic convulsion, transfusion response, stress disorder, etc.

Objective To investigate the association between Gal-3 and the effect of perindopril on ventricular remodeling in ischemic heart failure rabbit.Methods A rabbit model of ischemic heart failure was made by ligationof the anterior descending branch of the coronary artery.Thirty rabbits were divided into sham operation group,heart failure group and perindopril group.Determination of cardiac function by echocardiography after 4 weeks of treatment respectively;mRNA expression and protein content of Gal-3 were detected by Real-time PCR or Western-blob.Serum Gal-3 level was determinated by ELISA.Results Compared with sham operation group,mRNA expression and protein content of Gal-3,type Ⅰ collagen and type Ⅲ collagen increased and the serum level of Gal-3 increased in heart failure group(P＜0.05);compared with heart failure group,mRNA expression and protein content of Gal-3,type Ⅰ collagen and type Ⅲ collagen decreased and the serum level of Gal-3 was reduced in perindopril group(P＜ 0.05).Gal-3 was negativelycorrelated with heart function(r=-0.925,P＜0.05).Conclusion Effect of perindopril inhibiting myocardial fibrosis,slowing the ventricular remodeling and improving heart function associated with level of Gal-3.

Objective To investigate the association between interleukin-17 A (IL-17 A) gene promoter polymorphism and blood lipid and inflammatory factors in coronary heart disease.Methods A total of 241 patients with coronary heart disease who were admitted to hospital from April 2010 to December 2016 were enrolled in this study.68 cases of healthy subjects were collected.IL-17 gene promoter rs8193036 genotype,blood lipid and inflammatory factors were detected and compared.Results Compared with the control group,the genotype CC,CT and TT of the rs8193036 genotype in the coronary heart disease group were significantly different (P＜0.05),and the frequency of C allele in the coronary heart disease group was significantly higher than that in the control group (P＜0.05).The levels of triglyceride,low-density lipoproteinCholesterol,high density lipoprotein cholesterol,interleukin-17a,interleukin-6,interleukin-8 and tumor necrosis factor alpha in CC genotype of tumor necrosis factor alpha group were significantly higher than those in tumor necrosis factor alpha group (P＜0.05),high density lipoprotein cholesterol decreased significantly (P＜0.05).Total cholesterol and low-density lipoprotein cholesterol had no significant differences (P ＞ 0.05).Conclusion The rs8193036 polymorphism of IL-17A gene promoter is associated with the pathogenesis of coronary heart disease.The C allele is an important genetic marker of coronary heart disease.The polymorphism of IL-17A promoter rs8193036 might affect coronary heart disease by increasing blood lipids and inflammation factors.

Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G₂/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm^3, (216.80±57.18)mm^3, (246.10±21.90)mm^3, (327.50±44.24)mm^3, (213.30±32.31)mm³ and (495.80±75.87)mm³ in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05). Conclusion Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.

One severely burned patient, caused by heat lead slag and combined with shock, was hospitalized in our burn unit on 2nd June, 2016. The patient received treatments including anti-shock, intensive care, anti-infection, and organ protection. On post injury day 16, the patient suffered outbreak of acute hemorrhagic necrotizing enteritis after eating dumplings. Plasma and albumin were given, octreotide was intravenously infused to inhibit the secretion of intestinal fluid, the broad-spectrum antibiotics were used for anti-infection, abdominal puncture and drainage were performed, sodium tanshinone ⅡA sulfonate was applied to improve the intestinal microcirculation, ulinastatin was applied to alleviate inflammatory reaction, somatostatin was given to reduce intestinal bleeding, and voriconazole was given for antifungal treatment. The patient gradually recovered and was finally cured and discharged. Among critically ill patients, gastrointestinal tract is not only the initiating organ of sepsis, but also one of the target organs which can be easily damaged during sepsis. This case reminds us the importance of gastrointestinal management in severely burned patients.

Purpose To assess right ventricular function and synchronous acute response in patients with chronic cardiac failure after cardiac resynchronization therapy (CRT) using equilibrium radionuclide angiography (ERNA).Materials and Methods Twenty-four chronic cardiac failure patients who accepted CRT were included (CRT group) and twenty healthy participants were also selected as the control group.ERNA was performed before and within 48 h after pacemaker implantation to calculate both right ventricular ejection fraction (RVEF) and RV dyssynchrony.RV dyssynchrony was defined as the standard right ventricular phase shift and right ventricular phase standard deviation (RVPS and RVPSD).Results The postoperative RVEF,RVPS and RVPSD in CRT group were significantly improved (P＜0.05).Fifteen patients (62.5％) were classified as acute responders,based on a reduction of at least 15％ in LV end-systolic volume immediately after CRT.The baseline RVEF in responders was higher than that in nonresponders (P＜0.05),while the RVPS and RVPSD were lower (P＜0.05).The postoperative RVPS and RVPSD decreased (P＜0.05),and the RVEF increased (P＜0.05) in both responders and nonresponders after pacemaker implantation,indicating that the right ventricular function and dyssynchrony in CRT group were both improved.Conclusion This study showed a significant improvement in RV ventricular systolic function and synchrony immediately after CRT.ERNA allows assessment of changes in RVEF and RV dyssynchrony before and after CRT implantation.

Objective To observe the expression pattern of galectin-3 in heart failure rabbits after myocardial infarction and to explore the effect of galectin-3 on myocardial fibrosis and ventricular remodeling.Methods The left anterior descending coronary arterys of the rabbits were ligatured for model preparation.Twenty male rabbits were randomly divided into control group and experimental group.The control group was treated by thoracotomy.Cardiac function were detected by cardiac uhrasonography before and after 2,4,6 weeks.Serum samples were collected and galectin-3 level of the samples were further tested with ELISA before and after 2,4,6 weeks.The expression of myocardial fibrosis was detected by Masson staining in the experimental group and the control group at 6 weeks after operation.galectin-3 and collagen Ⅰ,collagen Ⅲ mRNA level of myocardial of the infracted zone were determinated via Real-Time PCR after 6 weeks operation.Calculate the ratio of collagen Ⅰ and collagenⅢ.Left ventricular mass were analysis and left ventricular hypertrophy index was calculated.Results Compared with the control group,the EF,EDD and LVPWD of the experimental group at 2,4 and 6 weeks after operation were significantly different(P ＜ 0.01).Serum galectin-3 level of the experimental group more than control group (P ＜0.05).correlation analysis showed that serum galectin-3 level was negatively correlated with EF (r =-0.84,P =0.009),and positively correlated with EDD(r =0.905,P =0.020).The mRNA expression of galectin-3,collagen Ⅰ and collagen Ⅲ were significantly increased in the experimental group(P ＜0.01).The mRNA expression of galectin-3,collagen Ⅰ and collagenⅢ were all higher in the experimental group than that in the non-infarcted area (P ＜ 0.01).The left ventricular mass and left ventricular hypertrophy index of the experimental group were significantly higher than control group (P ＜ 0.01).Under the optical microscope,the myocardial cells in the experimental group were disordered,necrosis,edema,hypertrophy and thickening of myocardial fibers.Microvascular wall thickening and visible around a large number of blue-green collagen fibers and surrounded by segmented myocardial cells,myocardial interstitial fibrosis,collagen deposition and accompanied by a large number of inflammatory cell infiltration.Conclusion Galectin-3 reflects the degree of myocardial fibrosis in heart failure,and is involved in the pathophysiology of ventricular remodeling,but the mechanism remains unclear.