Considering the end of global emergency status of Coronavirus-19 (COVID-19) and the persistent risk of reinfection for healthcare workers (HCWs), it is important to evaluate the attitude of the HCWs toward reinfecting with COVID-19. To gather information about participants' concerns regarding reinfection with COVID-19, a comprehensive online questionnaire was administered to all individuals involved in the study. DASS-21 was used to assess their mental health. Logistic regression was used to evaluate the factors associated with fear of reinfection. A total of 982 questionnaires were collected for this study, with only 503 questionnaires included in the final analysis. Of the 503 respondents, 201 (39.96%) feared reinfection with COVID-19. Three factors emerged as significantly associated with the fear of reinfection: (a) having been infected with COVID-19 before, (b) feeling that COVID-19 had a lasting effect on one's life, and (c) experiencing anxiety. The most common factors reported by those who feared reinfection were: concern about the negative effects of reinfection on their physical health, worry about the possible long-term complications of reinfection, and belief that reinfection would not have a big impact. And the mental state of HCWs has improved and become more optimistic. Although the morale of HCWs has improved, it remains evident that a significant portion of them still have concerns about reinfection and continue to experience anxiety. Moving forward, it is crucial to provide timely psychological care and support to HCWs, alongside reinforcing efforts in epidemic management.

Objective To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS). Methods Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model. Results XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model. Conclusion The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.

The pyruvate kinase M2 (PKM2) can significantly affect the differentiation of Th17 and Treg cells; thus, it is considered a promising target for UC therapy. Herein, five series of costunolide (Cos) derivatives are designed, synthesized, and biologically evaluated. Among them, D5 exhibits excellent immunomodulatory activity against T-cell proliferation and potent PKM2 activating activity. Meanwhile, it has been confirmed that D5 can also covalently interact with Cys424 of PKM2. The molecular docking and molecular dynamic (MD) studies indicate that difluorocyclopropyl derivative of D5 improves the protein-ligand interaction by interacting with Arg399 electrostatically. Furthermore, D5 significantly dampens the differentiation of Th17 but not Treg cells to recover the Th17/Treg balance, which is attributed to the suppression of PKM2-mediated glycolysis. Oral administration of D5 ameliorates the symptoms of dextran sulfate sodium (DSS)- and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced colitis in mouse model. Collectively, D5 has the potential to be developed as a novel anti-UC candidate.

BackgroundThe coronavirus disease 2019 (COVID-19) has affected approximately 2 million individuals worldwide; however, data regarding fatal cases have been limited.ObjectiveTo report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30, 2019 and March 12, 2020.MethodsThe demographic data, signs and symptoms, clinical course, comorbidities, laboratory findings, computed tomographic (CT) scans, treatments, and complications of the patients with fatal cases were retrieved from electronic medical records.ResultsThe median patient age was 69.5 (interquartile range: 63.0-77.25) years, and 80% of the patients were over 61 years. A total of 112 (69.1%) patients were men. Hypertension (45.1%) was the most common comorbidity, while 59 (36.4%) patients had no comorbidity. At admission, 131 (81.9%) patients had severe or critical COVID-19, whereas 39 (18.1%) patients with hypertension or chronic lung disease had moderate COVID-19. In total, 126 (77.8%) patients received antiviral treatment, while 132(81.5%) patients received glucocorticoid treatment. A total of 116 (71.6%) patients were admitted to the intensive care unit (ICU), and 137 (85.1%) patients received mechanical ventilation. Most patients received mechanical ventilation before ICU admission. Approximately 93.2% of the patients developed respiratory failure or acute respiratory distress syndrome. There were no significant differences in the inhospital survival time among the hospitals (P=0.14).ConclusionYoung patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes. The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.

Coronavirus disease 2019（COVID-19） has inarguably caused the most challenging pandemic. In less than 2 years, greater than 200 million cases of COVID-19 and 4.5 million deaths have been reported worldwide [1] . The treatment strategy of an emerging infectious disease is a huge challenge for clinical practitioners because of missing key knowledge about the disease.

Background Falls are an important cause of injury and death of older people. Hence, analyzing the multifactorial risk of falls from past cases to develop multifactorial intervention programs is clinically significant. However, due to the small sample size, there are few studies on fall risk analysis of clinical characteristics of fallers, especially among older hospitalized patients. Methods We collected data on 153 inpatients who fell (age ≥ 60 years) from the hospital nursing adverse event reporting system during hospitalization at Shandong Provincial Hospital Affiliated to Shandong First Medical University, China, from January 2018 to December 2020. Patient characteristics at the time of the fall, surrounding environment, primary nurse, and adverse fall events were assessed. The enumeration data were expressed as frequency and percentage, and the chi-squared was performed between recurrent fallers and single fallers, and non-injurious and injurious fall groups. Results Cross-sectional data showed 18.3% of the 153 participants experienced an injurious fall. Compared with single fallers, a large proportion of older recurrent fallers more often experienced preexisting conditions such as cerebrovascular disease or taking hypoglycemic drugs. They were exposed to higher risks and could experience at least 3 fall times in 3 months. Besides, the credentials of their responsible nurses were often higher. Factors that increased the risk of a fall-related injury were hypoglycemic drugs (OR 2.751; 95% CI 1.114–6.795), and nursing adverse events (OR 47.571; 95% CI 14.392–157.247). Older inpatients with bed rails (OR 0.437; 95% CI 0.190–1.005) or falling at the edge of the bed (OR 0.365; 95% CI 0.138–0.964) were less likely to be injured than those without bed rails or not falling at the edge of the bed. Fall risks were significantly correlated with more severe fall-related injuries. Older patients with moderate (OR 5.517; CI 0.687–44.306) or high risk (OR 2.196; CI 0.251–19.219) were more likely to experience fall-related injuries than those with low risk. Conclusions Older inpatient falls are an ongoing challenge in hospitals in China. Our study found that the incidence of fall-related injuries among inpatients aged ≥ 60 years remained at a minor level. However, complex patient characteristics and circumstances can contribute to fall-related injuries. This study provides new evidence on fall-related injuries of older inpatients in China. Based on the factors found in this study, regular fall-related injury epidemiological surveys that investigate the reasons associated with the injuries were crucial when considering intervention measures that could refine fall-related injuries. More prospective studies should be conducted with improved and updated multidisciplinary fall risk assessment and comprehensive geriatric assessment as part of a fall-related injury prevention protocol.

Background: Wu-Mei-Wan (WMW), a traditional Chinese medicine, has been applied in the treatment of gastro-intestinal diseases with long-term diarrhea and mucopurulent bloody stool as the main symptoms since ancient times. Studies have shown that WMW inhibits intestinal inflammation, repairs damaged intestinal mucosa, resists colon necrosis, and resists intestinal fibrosis. However, the specific mechanism of action is not yet clear. Objective: Ulcerative colitis (UC), an intestinal disease with intestinal inflammation and injury as the main pathological manifestations, is one of the high-risk factors for colon cancer. Inhibiting the inflammatory response and promoting colonic epithelial repair are critical to the treatment of UC. However, there is still a lack of remedies with satisfactory curative effects. In this study, the role of WMW in dextran sulfate sodium (DSS)-induced colitis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and tissue repair. Methods: DSS was used to induce colitis in mice and the therapeutic effect of WMW was analyzed by disease activity score, histopathological score, colon length measurement, serum cytokine detection, and flow cytometry. Macrophage activation and colonic stem cell proliferation were observed by immunohistochemistry. The expression of critical molecules in macrophage activation and colonic stem cell proliferation signaling pathways in colon tissue was detected with immunohistochemistry, immunofluorescence staining, RT-qPCR, and Western blot. Results: WMW could significantly alleviate DSS-induced colitis. We showed that WMW could reduce disease activity, reduce pathological scores, limit weight loss, inhibit colon shortening, inhibit inflammatory factor secretion, attenuate inflammatory response, and promote the repair of damaged colonic epithelium. WMW inhibited the activation of colonic macrophages, and its mechanism might be inhibiting the Notch/NF-kappa B/NLRP3 pathway; WMW promoted the proliferation of colonic stem cells, and its mechanism was associated with the regulation of the Hippo/YAP signaling pathway. Conclusion: The results of this study suggested that WMW could treat UC via a mechanism that inhibited the intestinal inflammatory response and repaired damaged intestinal mucosa.

目的 探讨脓毒症患者六经辨证分型与T淋巴细胞亚群及单核细胞免疫功能的关系.方法 将2019年1月至2022年2月北京中医药大学深圳医院(龙岗)重症监护病房(ICU)收治的102例脓毒症患者按六经辨证分为太阳病、阳明病、少阳病、太阴病、少阴病、厥阴病6个证型.入组24 h内检测不同证型患者人白细胞DR抗原(HLA-DR)、T淋巴细胞亚群〔CD4+T细胞(CD4+)、辅助性T细胞2(Th2)、调节性T细胞(Treg)〕、降钙素原(PCT)、中心静脉血氧饱度(ScvO2)水平;并观察各证型患者急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、ICU住院时间和28 d病死率的变化.结果 ① 从太阳病到少阴病,HLA-DR、CD4+逐渐降低,Th2、Treg逐渐增高,其中太阴病HLA-DR、CD4+明显低于太阳病(HLA-DR:0.36±0.04比0.41±0.06,CD4+:0.37±0.05比0.43±0.06,均P<0.05),Th2、Treg明显高于太阳病(Th2:0.0302±0.0062比0.0265±0.0042,Treg:0.119±0.024比0.095±0.020,均P<0.05);少阴病HLA-DR和CD4+水平均明显低于太阳病、阳明病、少阳病(HLA-DR:0.33±0.05比0.41±0.06、0.39±0.05、0.37±0.06,CD4+:0.36±0.05比0.43±0.06、0.40±0.06、0.40±0.05),Th2、Treg则明显高于太阳病、阳明病、少阳病(Th2:0.0342±0.0068比0.0265±0.0042、0.0278±0.0051、0.0293±0.0052,Treg:0.128±0.025比0.095±0.020、0.102±0.020、0.107±0.023,均P<0.05).② 从太阳病到少阴病,APACHEⅡ评分、PCT逐渐增高,ScvO2逐渐下降,其中太阴病APACHEⅡ评分和PCT水平明显高于太阳病、阳明病〔APACHEⅡ评分(分):22.37±6.36比15.24±5.51、17.85±5.34,PCT(μg/L):32.75±9.31比24.42±8.58、26.83±8.52,均P<0.05〕,ScvO2明显低于太阳病、阳明病(0.629±0.008比0.685±0.009、0.665±0.009,均P<0.05);少阴病APACHEⅡ评分和PCT水平明显高于太阳病、阳明病、少阳病〔APACHEⅡ评分(分):24.52±6.59比15.24±5.51、17.85±5.34、19.22±6.40,PCT(μg/L):35.42±9.48比24.42±8.58、26.83±8.52、28.39±7.39,均P<0.05〕,ScvO2明显低于太阳病、阳明病、少阳病(0.595±0.007比0.685±0.009、0.645±0.008,均P<0.05).③ 少阴病28 d病死率明显高于太阳病〔53.57％(15/28)比25.00％(5/20),P<0.05〕,年龄、ICU住院时间明显高于太阳病、阳明病、少阳病〔年龄(岁):75.28±9.46比66.51±7.55、68.24±7.71、70.44±6.47,ICU住院时间(d):14.57±5.48比9.31±3.22、9.96±3.28、11.30±3.50,均P<0.05〕.结论 脓毒症患者T淋巴细胞亚群、HLA-DR的表达与六经传变存在对应关系;六经辨证分型能评估脓毒症患者的免疫功能、病情严重程度及转归.

Background Understanding the influenza-like illness (ILI) incidence, circulation pattern of virus strains and spatiotemporal pattern of influenza transmission are important for designing control interventions. Based on the 10 years' surveillance data, we aimed to provide a baseline characterization and the epidemiology and dynamics of influenza virus in Shandong. Methods We extracted surveillance and laboratory testing data. We estimated the ILI incidence and analyzed the predominant virus. A wavelet power analysis was used to illustrate the periodicity. In addition, we applied a linear regression model to characterize the correlation of influenza seasonality with longitude. Results The average ILI incidence was estimated to be 3744.79 per 1 million (95% confidence interval [CI]: 2558.09-4931.45) during 2009-2018. Influenza A/H1N1 and A/H3N2 strains predominated in the most influenza seasons in Shandong. The annual amplitude of influenza epidemics decreased with longitude (P < 0.05). In contrast, the epidemic peak of influenza emerged earlier in the western region and increased with longitude in influenza A (P < 0.05). The annual peak of the influenza B epidemic lagged a median of 4.2 weeks compared with that of influenza A. Conclusions The development or modification of seasonal influenza vaccination strategies requires the recognition that the incidence is higher in preschool- and school-aged children. Although seasonal influenza circulates annually in Shandong, the predominant virus strain circulation pattern is extremely unpredictable and strengthening surveillance for the predominant virus strain is necessary. Lower longitude inland regions need to take nonpharmaceutical or pharmaceutical interventions in advance during influenza high-occurrence seasons.

本文通过观察深圳地区感染新型冠状病毒患者临床症状,从《伤寒论》角度探讨新型冠状病毒感染患者肺炎形成机制,从临床症状结合理论分析,大多数肺部感染患者多涉及太阳经、阳明经、少阳经和太阴经,并提出宣肺解表、和解少阳、辛散水湿和清热润燥的治法和代表方药进行治疗,防止病情加重而出现喘脱.

目的 观察破格救心汤治疗脓毒性休克的临床疗效.方法 脓毒性休克患者92例随机分为对照组与观察组各46例.两组均给予常规治疗,观察组加用破格救心汤治疗.分析两组中医证候疗效,检测两组患者治疗前后的急性生理和慢性健康状况评分(APACHEⅡ)、全身感染相关器官功能衰竭评分(SOFA)、平均动脉压(MAP)、中心静脉血氧饱和度(SCvO2)、血乳酸(Lac)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、降钙素原(PCT),并计算乳酸清除率,记录机械通气时间、血管活性药物使用时间、28 d病死率.结果 观察组的中医疗效总有效率为84.78％,高于对照组的71.74％ (P＜ 0.05).与治疗前比较,两组APACHEⅡ、SOFA评分及血清TNF-α、IL-6、hs-CRP、PCT均明显降低,且观察组降低更明显(P＜0.05);与治疗前比较,两组MAP、ScvO2均明显升高,且观察组升高更明显(P＜0.05);观察组12、24、48 h血Lac浓度及乳酸清除率均显著低于对照组(P＜0.05);两组机械通气时间、血管活性药物使用时间、28 d病死率差异无统计学意义(P＞0.05).结论 破格救心汤可以提高脓毒性休克患者的中医证候疗效,改善病情,显著减轻炎症反应.

目的 观察大黄附子汤治疗脓毒症肺损伤患者的临床疗效.方法 选择2018年6月至2020年6月北京中医药大学深圳医院(龙岗)重症监护病房(ICU)收治的60例脓毒症肺损伤患者,采用随机数字表法分为对照组和治疗组,每组30例.所有患者均给予常规治疗.对照组在常规治疗基础上加用枸橼酸莫沙必利片和双歧杆菌三联活性胶囊治疗;治疗组在常规治疗基础上加用大黄附子汤(组成:大黄12?g,制附子15?g,细辛6?g)治疗,每剂煎煮成200?mL,每日1剂,分3次服用;两组疗程均为8?d.观察两组患者治疗前后序贯器官衰竭评分(SOFA)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、胃肠功能障碍评分、肺部超声B线评分、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、氧合指数(PaO2/FiO2)变化;记录两组患者28?d病死率、机械通气时间、ICU住院时间和总住院时间.结果 两组患者治疗3?d肺部超声B线评分较治疗前略降低,治疗5?d和8?d肺部超声B线评分均较治疗前明显降低,以治疗组降低更明显(分:治疗5?d为12.78±2.13比14.32±2.40,治疗8?d为8.59±1.16比9.43±1.35,均P<0.05).随治疗时间延长,治疗组患者治疗3、5、8?d?APACHEⅡ评分、SOFA评分、胃肠功能障碍评分均呈明显降低趋势,PaO2、PaO2/FiO2均呈明显升高趋势,且上述指标与对照组同时间点比较差异均有统计学意义,以治疗8?d变化最明显〔APACHEⅡ评分(分):15.74±3.62比18.21±3.82,SOFA评分(分):3.43±1.22比4.32±1.43,胃肠功能障碍评分(分):6.44±1.49比7.37±1.51,PaO2(mmHg,1?mmHg≈0.133?kPa):86.81±9.87比81.76±9.45,PaO2/FiO2(mmHg):295.88±57.47比265.89±51.64,均P<0.05〕.治疗组患者机械通气时间、ICU住院时间和总住院时间均较对照组明显缩短〔机械通气时间(d):7.35±2.52比9.32±3.31,ICU住院时间(d):9.46±4.23比12.24±5.18,总住院时间(d):14.39±6.72比18.46±7.22,均P<0.05〕;两组患者28?d病死率比较差异无统计学意义〔20.00％(6/30)比33.33％(10/30),P>0.05〕.结论 大黄附子汤能促进脓毒症肺损伤患者胃肠功能恢复,减轻肺水肿,改善呼吸功能,缩短住院时间,缓解病情.

目的:探讨茯苓四逆汤调节TLR-4/NF-κB通道对脓毒症大鼠心肌抑制的保护作用机制.方法:SPF级SD雄性大鼠120只,随机分成6组:正常组、假手术组、模型组,中药低、中、高剂量组.通过盲肠结扎穿孔法(CLP法)制作脓毒症模型.造模后6h开始给药,持续给药3d.正常组、假手术组、模型组予等量生理盐水,中药各剂量组予相应剂量茯苓四逆汤,均为灌胃给药.观察大鼠生存状态,于术前和术后24h、48h、72h各选5只大鼠处死,采用Western blotting法及QPCR检测心肌组织NF-κB、H-FABP的蛋白和TLR-4的基因表达,同时以ELISA法检测心肌细胞TNF-α、IL-6含量.结果:与正常组比较,模型组及中药各剂量组TNF-α、IL-6水平及NF-κB、H-FABP蛋白表达明显升高,TLR-4基因表达亦增高;与模型组同时间点比较,中药各剂量组TNF-α、IL-6水平明显下降,NF-κB和H-FABP蛋白水平比较也有统计学差异;中药各剂量组同时间比较发现,剂量越高,其TNF-α、IL-6水平下降越明显,下调NF-κB和H-FABP蛋白表达水平越明显,TLR-4 mRNA转录水平降低的越明显,差异均有统计学意义.结论:茯苓四逆汤能减轻脓毒症大鼠心肌抑制,通过抑制炎症反应,负反馈调节TL R-4/NF-κ B信号通路,从而缓解心肌抑制.

Overcoming the FLT3-ITD mutant has been a promising drug design strategy for treating acute myeloid leukemia (AML). Herein, we discovered a novel FLT3 inhibitor 17, which displayed potent inhibitory activity against the FLT3-ITD mutant (IC50 = 0.8 nM) and achieved good selectivity over c-KIT kinase (over 500-fold). Compound 17 selectively inhibited the proliferation of FLT3-ITD-positive AML cell lines MV4-11 (IC50 = 23.5 nM) and MOLM-13 (IC50 = 35.5 nM) and exhibited potent inhibitory effects against associated acquired resistance mutations. In cellular mechanism studies, compound 17 strongly inhibited FLT3-mediated signaling pathways and induced apoptosis by arresting the cell cycle in the sub-G1 phase. In in vivo studies, compound 17 demonstrated a good bioavailability (73.6%) and significantly suppressed tumor growth in MV4-11 (10 mg/kg, TGI 93.4%) and MOLM-13 (20 mg/kg, TGI 98.0%) xenograft models without exhibiting obvious toxicity. These results suggested that compound 17 may be a promising drug candidate for treating FLT3-ITD-positive AML.

Background Since the outbreak of COVID-19, the application of appropriate treatment strategy for COVID-19 patients, notably for the severe patients, was a huge challenge in case management. Therefore, we aimed to evaluate the effectiveness of antiviral treatment in severe COVID-19 patients.Methods A retrospective cohort study was conducted from January 8, 2020 to March 9, 2020 in four designated hospitals of COVID-19 in Wuhan, China. 138 severe COVID-19patients with above 18 years were included in this study. 109 patients receiving the antiviral treatment were selected in antiviral group. The remaining 29 patients were in control group. The primary outcome of the study was in-hospital death and length of hospitalization. Secondary outcomes included ICU admission, length of stays in ICU, use of mechanical ventilation, length of mechanical ventilation, and the development of complications. Univariate analysis and Kaplan-Meier curves were used to examined the association between antiviral treatment and the clinical outcomes of the COVID-19 patients.Results 48 (44.0%) and 15 (51.7%) deaths were occurred in antiviral and control groups, respectively. Antiviral treatment was not associated with the rate of fatal outcome in COVID-19 patients (P > 0.05). Among the survival patients, the median length of hospitalization was 11.0 days (IQR: 6.5–18.0) and 16.0 days (IQR: 8.5–26.0) in antiviral and control groups, respectively. No significant association was identified between the antiviral treatment and the length of hospitalization in survival patients (P > 0.05). Moreover, the antiviral treatment was not statistically associated with ICU admission, mechanical ventilation and length of mechanical ventilation (P > 0.05, respectively). However, the length of ICU stays in deaths was different both groups (P < 0.05). The median length of ICU stays in deaths was 7.0 days (IQR: 3.0-14.3) and 15.5 days (IQR: 8.3–21.8) in antiviral and control groups, respectively. The occurrence of majority of complications were similar both groups. Sepsis was the single complication in which the occurrence rates were statistical different between the antiviral group and control group (40.4% vs 13.8%, P < 0.01).Conclusion No benefit of antiviral treatment in severe COVID-19 patients was observed in our study. Clinical physicians should cautiously prescribe the antiviral drugs in severe COVID-19 patients.

Understanding the epidemiological and clinical characteristics of fatal cases infected with SARS-CoV-2 is import to develop appropriate preventable intervention programs in hospitals. Demographic data, clinical symptoms, clinical course, co-morbidities, laboratory findings, CT scans, treatments and complications of 162 fatal cases were retrieved from electric medical records in 5 hospitals of Wuhan, China. The median age was 69.5 years old (IQR: 63.0-77.25; range: 29-96). 112 (69.1%) cases were men. Hypertension (45.1%) was the most common co-morbidity, but 59 (36.4%) cases had no co-morbidity. At admission, 131 (81.9%) cases were assessed as severe or critical. However, 39 (18.1%) were assessed as moderate. Moderate cases had a higher prevalence of hypertension and chronic lung disease comparing with severe or critical cases (P<0.05, respectively). 126 (77.8%) and 132 (81.5%) cases received antiviral treatment and glucocorticoids, respectively. 116 (71.6%) cases were admitted to ICU and 137 (85.1%) cases received mechanical ventilation. Respiratory failure or acute respiratory distress syndrome (93.2%) was the most common complication. The young cases of COVID-19, without co-morbidity and in a moderate condition at admission could develop fatal outcome. We need to be more cautious in case management of COVID-19 for preventing the fatal outcomes.

ETHNOPHARMACOLOGICAL RELEVANCE:Xuebijing (XBJ) injection is a Chinese medicine containing extracts from Carthamus tinctorius L. (Carthami Flos, hong hua, Asteraceae), Paeonia lactiflora Pall. (Paeoniae radix rubra, chi shao, Ranunculaceae), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong, Umbelliferae), Salvia miltiorrhiza Bge. (Salviae miltiorrhizae Radix Et Rhizoma, dan shen, Labiatae) and Angelica sinensis (Oliv.) Diels (Angelicae sinensis Radix, dang gui, Umbelliferae). It has been approved for the treatment of sepsis in China since 2004 and has been widely used as an add-on treatment for sepsis or septic shock with few side effects.AIM OF THE STUDY:The aim of the present review was to analyse up-to-date information related to the treatment of sepsis with XBJ, including the bioactive constituents, clinical studies and potential mechanisms, and to discuss possible scientific gaps, to provide a reliable reference for future studies.MATERIALS AND METHODS:Scientific resources concentrating on treating sepsis with XBJ were searched through PubMed, the Chinese National Knowledge Infrastructure (CNKI) and WanFang databases from inception to November 2018. Dissertations were also searched, and eligible dissertations were selected. Studies related to the identification of constituents, bioactive components and their targets of action or pathways, clinical trials, and animal or cellular experiments that explored pharmacological mechanisms were manually selected. The quality of reporting and methodology of the included pharmacological experiments were assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool.RESULTS:A total of 108 relative studies were eventually included, containing 12 bioactivity research studies, 10 systematic reviews on clinical trials and 86 animal or cellular experiments. We noted that as identification methods progressed, further constituents could be detected in XBJ. XBJ was also found to have "multi-ingredient, multi-target and multi-pathway" effects. The systematic review revealed that XBJ could improve the 28-day mortality and other indexes, such as the APACHE II score, body temperature, and white blood cell (WBC) count, to some extent. A major organ protection effect was demonstrated in septic rats. Pharmacological investigations suggested that XBJ acts in both the early and late stages of sepsis by anti-inflammatory, anti-coagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms. However, most of the included studies were poorly reported, and the risk of bias was unclear.CONCLUSIONS:With respect to the multiple therapeutic mechanisms contributing to both the early and late stages of sepsis, the multiple effective constituents detected and randomized controlled trials (RCTs) performed to prove its efficacy, XBJ is a promising therapy for the treatment of sepsis. However, although XBJ has shown some efficacy for the treatment of sepsis, there are currently some scientific gaps. More studies concerning the pharmacokinetics, interactions with antibiotics, real-world efficacy and safety, pharmacological mechanisms of the bioactive components and large-scale clinical trials should be conducted in the future.

Based on fragment-based virtual screening and bioisoterism strategies, novel indazole and pyrazolo[3,4-b] pyridine derivatives as HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDACs, especially compounds 15k and 15m were identified as potent inhibitors of HDAC1 (IC50 = 2.7 nM and IC50 = 3.1 nM), HDAC2 (IC50 = 4.2 nM and IC50 = 3.6 nM) and HDAC8 (IC50 = 3.6 nM and IC50 = 3.3 nM). Further anti-proliferation assays revealed that compounds 15k and 15m showed better anti-proliferative activities against HCT-116 and HeLa cells than positive control SAHA. The western blot analysis results indicated that compounds 15k and 15m noticeably up-regulated the level of acetylated α-tubulin and histone H3. In addition, the two compounds 15k and 15m could arrest cell cycle in G2/M phase and promote cell apoptosis, which was similar as the reference compound SAHA. Through the molecular docking and dynamic studies, the potent HDAC inhibitory activities mainly caused by van der Waals and electrostatic interactions with the HDACs.

BACKGROUND:H-type hypertension is a kind of cardiovascular disease that threatens human life and health seriously. Banxia Baizhu Tianma Tang (BBTT) has been used widely for H-type hypertension while its effective evidence is not clear. Hence, we provide a systematic review protocol to evaluate the efficacy and safety of BBTT in the treatment of H-type hypertension. METHODS:Nine databases including Cochrane Library, PubMed, EMBASE, WOS, Medline, CNKI, WangFang, CBM, and VIP will be searched from their inception to October 2019. All randomized controlled trials (RCTs) of BBTT for H-type hypertension will be included. The language is limited to Chinese and English. The primary outcome measure will be the major adverse cardiac and cerebral events (MACCE). The entire process will include study selection, data extraction, assessment of bias risk, data synthesis. Data analysis will be performed using RevMan V.5.3.5 (The Cochrane Collaboration, Oxford, UK). RESULTS:This study will evaluate the efficacy and safety of BBTT in the treatment of H-type hypertension from several aspects, including MACCE, blood pressure (BP), blood lipids, inflammation indicators and homocysteine (Hcy). CONCLUSION:This systematic review will provide evidence for determining whether or not BBTT is an effective and safe intervention for H-type hypertension. PROSPERO REGISTRATION NUMBER:PROSPERO CRD 42019131491.

Background: Primary osteoporosis (POP) is one kind of global disease, as a serious threat to human health. Liuwei Dihuang Decoction (LWDHD) has been recommended to treat osteoporosis alone or combined with medicine in China; however, its efficacy is unclear. The object of this systematic review and meta-analysis is to evaluate the efficacy and safety of LWDHD in the management of POP. Methods: We will search The Cochrane Library, Medline, PubMed, Elsevier, Springer, Web of Science, Ovid, WHO ICTRP, CNKI, CBM, VIP, and WanFang Database from their inception to February 2019. All randomized controlled trials (RCTs) of LWDHD for the treatment of POP will be included. The language is limited to Chinese and English. The fracture incidence will be accepted as the primary outcomes. Data synthesis, subgroup analysis, sensitivity analysis will be performed by using RevMan V.5.3.5 software. Results: A high-quality synthesis of current evidence for the treatment of POP with LWDHD will be provided from efficacy and safety. Conclusion: This systematic review will generate evidence for judging whether LWDHD is an effective and safe intervention for POP or not. PROSPERO registration number: PROSPERO CRD 4201926066.