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Sepsis is a systemic inflammatory response initiated by an infection, which can lead to multi-organ dysfunction. The pathophysiology of sepsis is complex, and treatment options are limited. Traditional antibiotic therapies have shown limitations, such as promoting the emergence of antibiotic-resistant bacteria and disrupting the natural microbiota. Consequently, there is a pressing need to explore diverse therapeutic approaches for sepsis management. Extracellular vesicles, which play a crucial role in cell-to-cell communication, are released by various cell types throughout the body and possess a membrane structure composed of a lipid bilayer. MicroRNAs may be encapsulated within these structures and can be selectively delivered to target recipient cells through the activation of cell surface receptors or via endocytosis and fusion, thereby modulating the biological functions of target cells. The article examines the pathological alterations that happen as sepsis progresses and the biological control of extracellular vesicles and microRNAs in sepsis. This review focuses on the role of extracellular vesicles and their microRNAs on controlling the inflammatory response, macrophage polarization, programmed cell death, endothelial dysfunction, and microcirculatory changes in sepsis. Furthermore, the obstacles encountered by this novel therapy are also examined.

Intracerebral hemorrhage (ICH) is a severe condition that devastatingly harms human health and poses a financial burden on families and society. Bcl-2 Associated X-protein (Bax) and B-cell lymphoma 2 (Bcl-2) are two classic apoptotic markers post-ICH. Beclin 1 offers a competitive architecture with that of Bax, both playing a vital role in autophagy. However, the interaction between Beclin 1 and Bcl-2/Bax has not been conjunctively analyzed. This review aims to examine the crosstalk between autophagy and apoptosis in ICH by focusing on the interaction and balance of Beclin 1, Bax, and Bcl-2. We also explored the therapeutic potential of Western conventional medicine and traditional Chinese medicine (TCM) in ICH via controlling the crosstalk between autophagy and apoptosis.

BackgroundMetabolic syndrome (MetS), or syndrome X, is a collection of metabolic illnesses that affect the body’s health, particularly insulin resistance and obesity. The prevalence of MetS is on the rise, particularly among younger individuals. Quercetin, a natural flavonoid found in many traditional Chinese medicines, can impact various pathways to disrupt the pathological advancement of MetS with few negative effects. The American Heart Association recently introduced a cardiovascular health assessment termed Life’s Essential 8 (LE8), which might impact the treatment of MetS.MethodsQuercetin targets and their functions in MetS pathways were identified using a network pharmacology method and molecular docking techniques. The study examined quercetin’s direct and indirect interactions with proteins linked to the pathogenic processes of MetS. Data were collected regarding the American Heart Association’s LE8 cardiovascular health indicators, which include health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure). The study assessed the connection between LE8 and the occurrence of MetS, taking into account dietary quercetin consumption as a variable of interest.ResultsThe negative correlation between MetS and LE8 indicates that individuals with higher LE8 scores are less likely to develop MetS. Individuals in the fully adjusted highest group (LE8 ≥ 80) demonstrated a 79% lower likelihood of developing MetS than those in the lowest group (OR = 0.21; 95% CI, 0.17–0.26, p

Background: Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment of Alzheimer's disease (AD). But the clinical effect of treating AD is uncertain. Objective: To systematically review the impact of KD on cognitive function in AD. Methods: We conducted a search of three international databases—PubMed, Cochrane Library, and Embase—to retrieve RCTs on the KD intervention for AD from the inception of the databases through October 2023. Two reviewers searched and screened the literature, extracted and checked relevant data independently, and assessed the risk of bias of the included studies. The meta-analysis was carried out utilizing RevMan 5.3 software. Results: A total of 10 RCTS involving 691 patients with AD were included. There were 357 participants in the intervention group and 334 participants in the control group. The duration of the KD intervention ranged from a minimum of 3 months to a maximum of 15 months. Meta-analysis results showed that KD could effectively improve the mental state of the elderly (NM scale) [MD = 7.56, 95%CI (3.02, 12.10), P = 0.001], MMSE [MD = 1.25, 95%CI (0.46, 2.04), P = 0.002], and ADAS-Cog [MD = −3.43, 95%CI (−5.98, −0.88), P = 0.008]. The elevation of ketone body (β-hydroxybutyric) [MD = 118.84, 95%CI (15.20, 222.48), P = 0.02] may also lead to the elevation of triglyceride [MD = 0.19, 95%CI (0.03, 0.35), P = 0.02] and low density lipoprotein [MD = 0.31, 95%CI (0.04, 0.58), P = 0.02]. Conclusion: Research conducted has indicated that the KD can enhance the mental state and cognitive function of those with AD, albeit potentially leading to an elevation in blood lipid levels. In summary, the good intervention effect and safety of KD are worthy of promotion and application in clinical treatment of AD.

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

Importance: The global COVID-19 pandemic does not appear to end in the near future. Currently, limited data are available on the risk factors for delayed viral clearance in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Objective: This study aimed to investigate the association of clinical characteristics and vaccination with prolonged viral clearance. Methods: This retrospective cohort included 16,985 patients who had contracted the SARS-CoV-2 Omicron variant between April 5 and May 30, 2022, in Shanghai, China, and had mild or no symptoms. The patients were admitted to the quarantine venue at the Shanghai New International Expo Center. Results: Of the 16,985 participants, the occurrence of viral clearance was ≤8 and > 8 days in 11,009 (64.8 %) and 5976 (35.2 %) participants, respectively. Risk factors related to patients who remained persistently polymerase chain reaction (PCR)-positive were sex (Male, odds ratio [OR] 1.221, p 35, OR 0.079, p

The endovascular intervention technique has gained prominence in the treatment of intracranial aneurysms due to its minimal invasiveness and shorter recovery time. A critical step of the intervention is the shaping of the microcatheter, which ensures its accurate placement and stability within the aneurysm sac. This is vital for enhancing coil placement and minimizing the risk of catheter kickback during the coiling process. Currently, microcatheter shaping is primarily reliant on the operator's experience, who shapes them based on the curvature of the target vessel and aneurysm location, utilizing 3D rotational angiography or CT angiography. Some researchers have documented their experiences with conventional shaping methods. Additionally, some scholars have explored auxiliary techniques such as 3D printing and computer simulations to facilitate microcatheter shaping. However, the shaping of microcatheters can still pose challenges, especially in cases with complex anatomical structures or very small aneurysms, and even experienced operators may encounter difficulties, and there has been a lack of a holistic summary of microcatheter shaping techniques in the literature. In this article, we present a review of the literature from 1994 to 2023 on microcatheter shaping techniques in endovascular aneurysm embolization. Our review aims to present a thorough overview of the various experiences and techniques shared by researchers over the last 3 decades, provides an analysis of shaping methods, and serves as an invaluable resource for both novice and experienced practitioners, highlighting the significance of understanding and mastering this technique for successful endovascular intervention in intracranial aneurysms.

Background Influenza is an acute infectious respiratory disease caused by the influenza virus that seriously damages human health, and the essential way to prevent influenza is the influenza vaccine. Vaccines without adjuvants produce insufficient specific antibodies and therefore require adjuvants to boost antibody titers. Microbes and hosts are a community that needs to “promote bacteria,” which could provide new value for the immune effect. Methods (1) The H1N1 influenza vaccine, in combination with Ginsenoside Rb1, was co-injected into mice intraperitoneally (I.P.). Then, immunoglobulin G and antibody subtype levels were tested by enzyme-linked immunosorbent assay (ELISA). Moreover, mice were infected with a lethal dose of the H1N1 influenza virus (A/Michigan/45/2015), and survival status was recorded for 14 days. Lung tissues were stained by hematoxylin and eosin (H&E), and ELISA detected inflammatory factor expression levels. (2) Mice were immunized with Ginsenoside Rb1 combined with quadrivalent influenza inactivated vaccine(IIV4), and then IgG levels were measured by ELISA. (3) Fresh stool was collected for fecal 16S rDNA analysis. Results Ginsenoside Rb1 boosted IgG and antibody subtypes in the H1N1 influenza vaccine, improved survival of mice after virus challenge, attenuated lung histopathological damage, and reduced inflammatory cytokines expression in IL-6 and TNF-α. The results of 16S rDNA showed that Rb1 decreased species diversity but increased species richness compared to the PBS group and increased the abundance of Akkermansiaceae and Murbaculaceae at the Family and Genus levels compared with the HA+Alum group. Conclusion Ginsenoside Rb1 has a boosting effect on the immune efficacy of the H1N1 influenza vaccine and is promising as a novel adjuvant to regulate the microecological balance and achieve an anti-infective effect.

Objective: To evaluate the prognostic ability of systemic immune-inflammation index (SII) combine with quick Sequential Organ Failure Assessment (qSOFA) criteria in predicting the 28-day mortality of sepsis. Methods: A retrospective cohort study was conducted, with the population comprised in whom sepsis was confirmed. Clinical and laboratory data recorded were analyzed. The score of Sequential Organ Failure Assessment (SOFA), SII, qSOFA were calculated. Multivariable regression, receiver operating characteristic (ROC) analysis and Kaplan-Meier method were used to identify and compared the predictors of prognosis among SOFA, qSOFA, and the combination of SII with qSOFA. Results: A total of 349 patients admitted from December 2020 and December 2022 were included in the cohort. 95 (27.2%) of whom had died by day 28. The SII, SOFA, and qSOFA scores were significant higher in the non-survivors than that of survivors (P 1.7668) and qSOFA (>1) represented a high risk level in 28-day mortality of sepsis, were performed and identified in Kaplan-Meier survival curves (log-rank test, HR: 6.942, 95% CI: 3.976–12.121; P

Objective: Reyanning mixture has been demonstrated to be effective in treating infected patients during the outbreak pandemic of SARS-CoV-2 Omicron variant of Coronavirus disease 2019 (COVID-19) in Shanghai 2022. The aim of this study is to further investigate the role of Reyanning mixture specifically in the treatment of elderly patients.Methods: This study enrolled 1,102 elderly patients who were infected with SARS-CoV-2 Omicron variant. Of these, 291 patients received Reyanning mixture in conjunction with conventional Western medicine treatment were assigned to the treatment group, while 811 patients only received conventional Western medicine treatment were assigned to the control group. Clinical parameters including hospitalization duration, viral shedding time, and Cycle Threshold (Ct) values of novel coronavirus nucleic acid tests, as well as adverse events were recorded and analyzed in both groups.Results: There was no significant difference in baseline characteristics between two groups. In comparison to the control group, the treatment group demonstrated a substantial difference in hospitalization duration (median: 8 days vs. 10 days, HR: 0.638, 95% CI: 0.558–0.731, p < 0.001). The treatment group also showed a significantly shorter viral shedding time compared to the control group (median: 7 days vs. 8 days, HR: 0.754, 95% CI: 0.659–0.863, p < 0.001). Multivariate Cox proportional-hazards model analysis indicated that the use of Reyanning mixture was closely associated with a reduction in hospitalization duration (HR: 1.562, 95% CI: 1.364–1.789, p < 0.001) and viral shedding time (HR: 1.335, 95% CI: 1.166–1.528, p < 0.001). In addition, during the treatment process, no serious adverse event occurred in either group.Conclusion: The improvement of clinical parameters in the treatment group indicate a promising therapeutic benefit of Reyanning mixture for elderly patients infected with SARS-CoV-2 Omicron variant in the present study. Further investigations are required to validate this finding by examining the underlying mechanism and function of Reyanning mixture.

The ongoing Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a huge threat to public health across the world. While vaccinations are essential for reducing virus transmission and attenuating disease severity, the nature of high mutation rate of SARS-CoV-2 renders vaccines less effective, urging quick development of effective therapies for COVID-19 disease. However, developing novel drugs remains extremely challenging due to the lengthy process and high cost. Alternatively, repurposing of existing drugs on the market represents a rapid and safe strategy for combating COVID-19 pandemic. Bronchodilators are first line drugs for inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Compared to other anti-inflammatory drugs repurposed for COVID-19, bronchodilators are unique in that they have both anti-inflammatory and bronchodilating properties. Whether the dual properties of bronchodilators empower them greater potential to be repurposed for COVID-19 is worth exploring. In fact, clinical and preclinical studies have recently emerged to investigate the benefits of bronchodilators such assalbutamol, formoterol and theophylline in treating COVID-19, and many of them have shown encouraging efficacy on attenuating disease severity of pneumonia and other associated symptoms. To comprehensively understand the latest progress on COVID-19 intervention with bronchodilators, this review will summarize recent findings in this area and highlight the promising clinical benefits and possible adverse effects of bronchodilators as therapeutic options for COVID-19 with a focus on β2 receptor agonists, anticholinergic drugs and theophylline.

ObjectiveStent-assisted coiling has been increasingly used in the treatment of intracranial aneurysms. However, its application in ruptured bifurcation aneurysms remains controversial and challenging. This study aimed to present the safety and feasibility of low-profile visualized intraluminal support (LVIS™, LVIS, and LVIS Jr.) stent for acutely ruptured bifurcation aneurysms.MethodsA total of 41 patients with acutely ruptured intracranial aneurysms arising at the bifurcation were treated with LVIS™ stent-assisted coiling in our hospital between January 2017 and December 2021. The clinical data and angiographic results of the patients were analyzed.ResultsAmong these patients, all stents were successfully implanted. According to the immediate angiographic results, 29 aneurysms (70.7%) were completely occluded. Intraoperative thrombosis and hemorrhage occurred in two and one cases, respectively. No post-operative thrombosis or rebleeding events were observed. The clinical follow-up of all patients revealed that 38 (92.7%) cases had favorable outcomes (modified Rankin scale: 0–2). The angiographic results available for the 36 patients during the follow-up period revealed complete occlusion was achieved in 30 patients (83.3%) and residual neck in six patients.ConclusionThe LVIS™ stent-assistant coiling is a safe and feasible option for acutely ruptured bifurcation aneurysms. Further studies with a prospective design, a larger sample size, and long-term follow-up are needed to validate these findings.

ObjectiveTo evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection.Materials and methodsHospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, “early clearance” and ≥15 days, “late clearance”).Results4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance.ConclusionThe number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant.Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed.Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender; After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05); The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group; both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01); gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group.Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

Background and aim: Presently, over-the-counter drugs that can treat upper respiratory tract infections (URTI) are rarely effective and safe. Chaiqin Qingning Capsule (CQQNC), a Chinese patent medicine, which has been verified by long-term clinical practice is recommended by Chinese experts for the treatment of URTI with fever. This study conducted a prospective, double-blinded, randomized, multicenter controlled trial to evaluate the effectiveness and safety of CQQNC in the treatment of URTI. Methods: The study was conducted at 4 clinical centers in China. Eligible subjects were recruited and randomized 1:1 to the CQQNC group and Qingkailing Capsule (QKLC) group. Both groups were administered orally three times a day for three consecutive days. Primary outcomes were the antipyretic onset time and the temperature recovery time. Secondary outcomes included the symptom disappearance rate, symptom score, and drug safety assessment. Results: A total of 269 subjects were analyzed (134 subjects in the CQQNC group, 135 subjects in the QKLC group). The antipyretic onset time and the temperature recovery time were significantly shortened in the CQQNC group (median: 5 h vs. 10 h, p

Abstract Background Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19. Methods/design This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial. Discussion The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR2000029869 . Registered on 15 February 2020

Abstract Background Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19. Methods/design This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial. Discussion This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029777 . Registered on 13 February 2020.

Xiyanping injection, a traditional Chinese medicine injection made of andrographolide sulfonate, consisting of well-defined ingredients with antiviral, antibacterial, anti-inflammatory and antipyretic efficacy, has been widely used for treating infectious diseases of respiratory and digestive systems. However, its wide applications may easily lead to unreasonable clinical medication. In order to guide the precise clinical application and rational use of Xiyanping injection, experts in related fields conducted systematically literature review, evaluated and deliberated the application of Xiyanping injection in treating acute infectious diseases using evidence-based medicine method, and jointly drafted the consensus to summarize types of acute infectious diseases in children and adults that can be treated with Xiyanping injection, and recommend the intervention time, usage and dosage, course of treatment and combined medication of the injection. Besides, the consensus elucidates the safety, precautions and contraindications of the injection, so as to provide guidance for clinical use.

Abstract Background Drug resistance in China is becoming a more and more serious issue. Infection by drug-resistant bacteria has become a major disease that seriously threatens the health of Chinese people and affects national medical finance. Therefore, it is of great scientific and clinical significance to actively carry out research on the prevention and treatment of infections by multi-drug resistant organisms (MDRO). Previous studies by the authors suggested that patients with hospital-acquired pneumonia caused by MDRO mostly showed the pathological state of “insufficient healthy Qi and internal accumulation of pathogenic Qi” and “acute deficiency syndrome” mainly characterized by Qi deficiency. Buzhong Yiqi decoction is a famous classic prescription in traditional Chinese medicine (TCM) for treating internal damage fever. This study intends to provide an evidence-based rationale for Buzhong Yiqi decoction in treating MDRO hospital-acquired pneumonia by conducting a multi-center randomized controlled clinical study. Methods/design This study is designed to be a multi-center randomized controlled study in which patients are assigned randomly into control (standard therapy) and trial (standard therapy plus Buzhong Yiqi decoction) groups. The patients will be selected from the emergency department and the ICU inpatient department of five study sites and will all be diagnosed with MDRO hospital-acquired pneumonia and meet the inclusion criteria. Forty patients are to be enrolled in each study site, resulting in a total of 200 patients in the study. The treatment course is 28 days. Discussion In this study: (1) the theory of “acute Qi deficiency” in MDRO hospital-acquired pneumonia is put forward for the first time, and the basic theories of TCM are further improved; (2) a multi-center randomized controlled clinical study will be performed for the first time with Buzhong Yiqi decoction, the classic prescription for reinforcing healthy Qi and eliminating pathogenic Qi, providing a reliable evidence-based rationale for the treatment of MDRO pulmonary infection with TCM; (3) the clinical application and modern disease spectrum of Buzhong Yiqi decoction is expanded, and the scientific notion of “treating different diseases with the same method” is enriched further. Trial registration China Clinical Trial Registry, ChiCTR1900022429. Registered on April 11, 2019. http://www.chictr.org.cn/listbycreater.aspx.

Fuyuan Xingnao decoction (FYXN), a traditional Chinese formula comprised of seven herbs, has been utilized to treat diabetes mellitus complicated with cerebral infarction (DMCI) for years. Yet, its protective and regulatory mechanism is poorly understood. The aim of the study is to investigate the effects of FYXN on DMCI in vitro and in vivo, as well as its mechanism in angiogenesis. For in vivo experiments, FYXN was administered to DMCI rats with streptozotocin (STZ) injection-induced diabetes. Then middle cerebral artery occlusion (MCAO) was conducted and the cerebral cortex sections of the rats were obtained. The ultrastructure of cerebral microvessels and new vessel density of ischemic penumbra were evaluated by the transmission electron microscopy (TEM) assay and immunohistochemistry, respectively. Protein and mRNA expression levels of Rab1/AT1R in cortex were assayed by Western blotting and real-time fluorescence quantitative real-time polymerase chain reaction (RT-qPCR). In vitro, FYXN serum was produced in rats on the fourth day 2 h after the last FYXN administration. Green fluorescence was observed after transfection with lentivirus packaged Rab1-WT or siRNA for 24 h. The activity of brain microvascular endothelial cells (BMECs) treated with sera from these rats was tested by MTT assay and Transwell assays, respectively. The expression of AT1R on the cell membrane and endoplasmic reticulum of BMECs was evaluated by immunofluorescence staining. Protein expression levels of signaling molecules in the Rab1/AT1R pathways were also detected. Results showed that in vivo, FYXN treatment significantly intensified CD31 staining in the cortical areas and enhanced the mRNA and protein levels of AT1R, Ang II, Rab1a, Rab1b and VEGF expression in ischemic cerebral cortex tissues. In vitro, the expression levels of AT1R, Ang II, Rab1a, Rab1b and VEGF in the cerebral infarction model group were significantly higher than those in the control group, with further increases after administration of FYXN drug serum. FYXN promoted the proliferation and migration of BMECs by activating the Rab1/AT1R signaling pathway. In conclusion, FYXN exerts a protective effect against DMCI by promoting angiogenesis via the Rab1/AT1R pathway, which provides strong evidence for the therapeutic effect of FYXN on DMCI.

Abstract Background Neck circumference (NC), representing upper body subcutaneous adipose tissue, may be correlated with increased risk of overweight/obesity, obstructive sleep apnoea, and metabolic and cardiovascular disease. However, the relationship between NC and the incidence of congestive heart failure (CHF) or mortality due to coronary heart disease (CHD) in a community-based population with and without sleep-disordered breathing (SDB) has not yet been clarified. Methods We performed a prospective study using the Sleep Heart Health Study (SHHS) cohort. Cox proportional hazards regression models were used to estimate the association of different levels of NC with CHF incidence or CHD mortality in 2234 individuals with SDB and 2199 without SDB, respectively. Results After adjusting for age, sex, and body mass index (BMI), NC was significantly associated with CHF when comparing the highest NC quartile group with the lowest (hazard ratio, HR, 2.265, 95% confidence interval, CI, 1.074–4.777) in the non-SDB population. This association diminished after further adjustment for other risk factors, but remained statistically significant, with an adjusted HR of 1.082 (95% CI 1.003–1.166) per unit increase in NC. Additionally, after adjustment for age, sex, and BMI, NC was also shown to be remarkably associated with CHD mortality (HR 1.141, 95% CI 1.014–1.282) per unit increase in NC in the non-SDB population but not in the SDB population. After adjustment for all the covariates, there was a significant association between NC and CHD death in those without SDB, with an adjusted HR of 1.134 (95% CI 1.001–1.284) per unit increase in NC. Conclusions NC may correlate with CHF incidence and CHD mortality in population without SDB. NC measurement may help risk stratification for cardiovascular diseases. Trial registration NCT00005275, January 1994.

Background. Multidrug-resistant (MDR) bacteria are the main cause of lower respiratory tract infections (LRTIs) with high mortality. The purpose of this study is to identify the risk factors associated with MDR by performing a systematic review and meta-analysis. Methods. PubMed, EMBASE (via Ovid), and Cochrane Library were systematically searched for studies on the risk factors for MDR bacteria in LRTIs as of November 30, 2019. Literature screening, data abstraction, and quality assessment of the eligible studies were performed independently by two researchers. Results. A total of 3,607 articles were retrieved, of which 21 articles representing 20 cohort studies published in English were included after title/abstract and full-text screening. Among the 21 articles involving 7,650 patients and 1,360 MDR organisms, ten reported the risk factors for MDR Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), ten for MDR GNB, and one for MDR GPB. The meta-analysis results suggested that prior antibiotic treatment, inappropriate antibiotic therapy, chronic lung disease, chronic liver disease and cerebral disease, prior MDR and PA infection/colonization, recent hospitalization, longer hospitalization stay, endotracheal tracheostomy and mechanical ventilation, tube feeding, nursing home residence, and higher disease severity score were independent risk factors for MDR bacteria. Conclusions. This review identified fourteen clinical factors that might increase the risk of MDR bacteria in patients with LRTIs. Clinicians could take into account these factors when selecting antibiotics for patients and determine whether coverage for MDR bacteria is required. More well-designed studies are needed to confirm the various risk factors for MDR bacteria in the future.