Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway in vivo and in vitro / 医学前沿

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

Population-based active screening strategy contributes to the prevention and control of tuberculosis / 浙江大学学报·医学版

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from "active discovery by X-ray examination" to "passive discovery by self-referral due to symptoms", and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

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.

BRICS report of 2018-2019: the distribution and antimicrobial resistance profile of clinical isolates from blood culture in China / 中华临床感染病杂志

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Progress on development of vaccines against 2019-nCoV / 中华临床感染病杂志

Since the outbreak of COVID-19 caused by the 2019-nCoV (SARS-CoV-2), with its high pathogenicity and contagiousness, it has posed a serious threat to global public health security. Up to now, the pathogenesis of 2019-nCoV is unclear, and there is no effective treatment. Vaccine as one of the most effective strategies to prevent virus infection has become a hot area. Based on the current understanding of 2019-nCoV, the development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, etc. In this review, we focus on the candidate targets of the novel coronavirus, and the types, development status and progress of 2019-nCoV vaccines in order to provide information for further research and prevention.

Hot and difficult issues related to prevention and control strategies of COVID-19 / 中华临床感染病杂志

The epidemic of COVID-19 has lasted for nearly a year, the number of confirmed cases worldwide is still rising, and the trend of the epidemic is unclear. How will be the further development of COVID-19 epidemic? What is the current status of research on new drugs for coronary virus disease? Will the vaccine currently used change the epidemic pattern? In the context of the normalization of the epidemic, whether the epidemiology of other respiratory viruses will change? This article will discuss and analyze these hot and difficult issues.

Gut bacteria and colorectal cancer: from pathogens to therapeutics / 中华临床感染病杂志

Colorectal cancer is a kind of cancer with high incidence in the world, and its etiology has not been completely understood yet. Gut bacteria take part in the occurrence and the progression of colorectal cancer in a number of ways, and thereinto, the enrichment of specific bacteria have been proved to be closely correlated with colorectal cancer. This article summarizes the changes of intestinal flora in patients with colorectal cancer and the bacteria related to colorectal cancer; and also discusses the strategies in treatment and prevention of colorectal cancer through regulating the intestinal flora.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Management of corona virus disease-19 (COVID-19): the Zhejiang experience / 浙江大学学报·医学版

The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Management of COVID-19: the Zhejiang experience / 浙江大学学报·医学版

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

New focus on microecology: intestinal fungi / 中华临床感染病杂志

It has been discovered that intestinal fungi play important roles in microecological systems of human body, which affect the human health by influencing gut microbiota directly or indirectly. This article reviews the research progress about the fungi-bacteria interaction, and effects of intestinal fungi and their products on host’s health. The article also discusses the correlation of intestinal fungi with inflammatory bowel disease, colorectal cancer, HBV-related liver diseases, metabolism-associated fatty liver disease and alcoholic liver disease, indicating that intestinal fungi are widely involved in the development of human diseases.

Risk factors for fatal outcome in patients with severe COVID-19: an analysis of 107 cases in Wuhan / 中华临床感染病杂志

Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.

Experiences in construction of infection disease outpatient service / 中华临床感染病杂志

The infectious disease outpatient service as a frontier is an important fulcrum of public health service. Its standardized construction is an important support for ensuring medical safety, reducing nosocomial infections, and controlling the epidemic of infectious diseases. The sub-specialty outpatient service of infection diseases includes fever outpatient service, intestinal outpatient service, tuberculosis outpatient service, AIDS outpatient service, liver disease outpatient service, etc. According to the characteristics of each subspecialty outpatient service and combining with clinical practice, we elaborated the setting norms of subspecialty outpatient service for common infectious diseases from the perspective of planning and design, building layout, equipment and facilities configuration, staffing, daily management and demonstration.

Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon α-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study / 中华临床感染病杂志

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

BRICS report of 2016-2017: the distribution and antimicrobial resistance profile of clinical isolates from blood culture in China / 中华临床感染病杂志

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2016 to December 2017. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI) 2019. WHONET 5.6 was used to analyze data.Results:During the study period, 8 154 bacterial strains were collected from 33 hospitals, of which 2 325 (28.5%) were Gram-positive bacteria and 5 829 (71.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (34.7%), Klebsiella pneumoniae (15.8%), Staphylococcus aureus (11.3%), coagulase-negative Staphylococci (7.4%), Acinetobacter baumannii (4.6%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.8%), Streptococci (2.9%), Enterobacter cloacae (2.7%) and Enterococcus faecalis (2.5%). Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) accounted for 34.2%(315/922) and 77.7%(470/605), respectively. No vancomycin-resistant Staphylococcus was detected. The resistance rate of Enterococcus faecium to vancomycin was 0.6%(2/312), and no vancomycin-resistant Enterococcus faecium was detected. The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus were 55.7%(1 576/2 831), 29.9%(386/1 289) and 38.5%(15/39), respectively. The incidences of carbapenem-resistance in Escherichia coli, Klebsiella pneumoniae were 1.2%(33/2 831), 17.5%(226/1 289), respectively. The resistance rates of Acinetobacter baumannii to polymyxin and tigecycline were 14.8%(55/372) and 5.9%(22/372) respectively, and those of Pseudomonas aeruginosa to polymyxin and carbapenem were 1.3%(4/315) and 18.7%(59/315), respectively. Conclusion:The surveillance results from 2016 to 2017 showed that the main pathogens of blood stream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen; the MRSA incidence was lower than other surveillance data in the same period in China; carbapenem-resistant Escherichia coli was at a low level during this surveillance, while carbapenem-resistant Klebsiella pneumoniae is on the rise.

Early antiviral therapy of abidor combined with lopinavir/ritonavir and re-combinant interferonα-2b in patients with novel coronavirus pneumonia in Zhejiang: A multicenter and prospective study / 中华临床感染病杂志

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.

Distribution and antimicrobial resistance profile of clinical bacterial isolates from blood culture in China, 2014-2015 / 中华临床感染病杂志

Objective To analyze the distribution and antimicrobial resistance profile of clinical bacterial strains isolated from blood culture in China.Methods Clinical bacterial strains isolated from blood culture from participating hospitals of Blood Bacterial Resistance Investigation Collaborative System (BRICS) during January 2014 to December 2015 were collected.Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods as recommended by US Clinical and Laboratory Standards Institute(CLSI)2018.The data were analyzed with Whonet 5.6 software.Results During the study period,4 801 clinical bacterial isolates were collected from 26 hospitals,of which 1 798 (37.5％) were Gram-positive bacteria and 3 003 (62.5％) were gram-negative bacteria.The top 10 isolates were Escherichia coli (33.8％),coagulase-negative Staphylococcus (19.0％),Klebsiella pneumoniae (11.9％),Staphylococcus aureus (10.1％),Acinetobacter baumannii (4.0％),Pseudomonas aeruginosa (3.8％),Streptococcus (3.0％),Enterobacter sulcus (2.9％),Enterococcus faecium (2.8％) and Enterococcus faecalis (1.8％).Methicillin-resistant Staphylococcus aureus (MRSA) and methicillinresistant coagulase-negative Staphylococcus (MRCNS) accounted for 33.9％ (165/487) and 56.9％ (520/913) of Staphylococcus aureus and coagulase-negative Staphylococcus respectively.No vancomycinresistant Staphylococcus was detected.The resistance rate of Enterococcus faecium to vancomycin was 0.7％ (1/135),and no vancomycin-resistant Enterococcus faecaliss was detected.The positive rates of extendedspectrum β-1actamases(ESBLs)-producing Escherichia coli,Klebsiella pneumoniae and Proteus were 56.9％ (923/1 621),30.1％ (172/572) and 29.2％ (7/24),respectively.The positive rates of carbapenemresistant Escherichia coli,Klebsiella pneumoniae,Enterobacter,Salmonella and Citrobacter were 1.2％ (20/1 621),7.2％ (41/572),4.3％ (6/141),1.5％ (1/67) and 2.9％ (1/34),respectively.The resistance rates of Acinetobacter baumannii to polymyxin and tegacycline were 2.6％ (5/190) and 8.9％ (17/190)respectively,and that of Pseudomonas aeruginosa to polymyxin and fosfomycin were 1.1％ (2/183)and 0.6％ (1/183),respectively.Conclusions The surveillance results from 2014 to 2015 show that the main pathogens of blood stream infection in China are Gram-negative bacteria,while Escherichia coli is the most common pathogen,the detection rate of MRSA is lower than other surveillance data in the same period in China;carbapenem-resistant Klebsiella pneumoniae and Escherichia coli are at a low level as shown in this surveillance.

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice / 医学前沿

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

New advances in drug therapy of chronic hepatitis B infection / 中华临床感染病杂志

Nucleos( t) ide analogs and interferon are currently the main drugs for the treatment of chronic hepatitis B; they can induce sustained virologic suppression of HBV DNA , but still can’t clear HBsAg effectively.With the further understanding of the biology and life cycle of HBV and the breakthrough of direct antiviral agent for HCV treatment , multiple new drugs aiming at ＂cure HBV＂and clear HBsAg are undergoing preclinical development and ／or clinical trials.This article reviews the latest advances in drug therapy of chronic hepatitis B infection.