Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Fetal monitoring is an essential component of the prenatal examination. With electronic fetal heart monitoring, clinicians can effectively monitor the intrauterine situation of the fetus, promptly detect fetal distress, and intervene early to reduce the occurrence of adverse outcomes in newborns. In recent years, the leaps in internet technology have enabled the widespread utilization of remote electronic fetal heart monitoring based on ultrasound technology. This paper reviews the application, effectiveness, and safety of remote fetal heart monitoring, and the satisfaction level of healthcare professionals with this technology in recent years and compares it with traditional fetal heart monitoring, aiming to provide reference and insights for clinical applications of remote fetal heart monitoring.

Fetal monitoring is an essential component of the prenatal examination. With electronic fetal heart monitoring, clinicians can effectively monitor the intrauterine situation of the fetus, promptly detect fetal distress, and intervene early to reduce the occurrence of adverse outcomes in newborns. In recent years, the leaps in internet technology have enabled the widespread utilization of remote electronic fetal heart monitoring based on ultrasound technology. This paper reviews the application, effectiveness, and safety of remote fetal heart monitoring, and the satisfaction level of healthcare professionals with this technology in recent years and compares it with traditional fetal heart monitoring, aiming to provide reference and insights for clinical applications of remote fetal heart monitoring.

ObjectiveTo compare the incidence of respiratory and allergic diseases in children in Xuhui District， Shanghai in 2013 and 2020， and to determine the influencing factors. MethodsAnnual average levels of air pollutants including PM_2.5， PM₁₀， O₃， SO₂， and NO₂ were collected and described in Shanghai from 2013 to 2020. A cross-sectional survey was conducted by using a questionnaire among grade 3 to 5 students in a school in Xuhui District， Shanghai， in September 2013 and 2020， respectively. The questionnaire collected variables including living environment， daily habits， family history of respiratory and allergic diseases， and incidence of these diseases in children. Chi-square test was used to determine the difference across respiratory and allergic diseases. Logistic regression was conducted to determine the influencing factors. ResultsA total of 1 398 valid questionnaires were collected （705 in 2013 and 693 in 2020）. Compared with 2013， annual average concentrations of PM_2.5， PM₁₀， O₃， SO₂， and NO₂ in 2020 significantly decreased. The prevalence of bronchial asthma， bronchitis， persistent cough and persistent expectoration in 2013 were significantly higher than those in 2020 （P<0.05） in Xuhui District. Multivariate analysis showed that severe air pollution， boys， parents with asthma or allergy， parents with higher educational levels， and more allergens in household were the risk factors associated with the incidence of bronchial asthma， bronchitis， allergic rhinitis and atopic eczema （P<0.05）. Parents with allergy history， high smoking frequency of family member， and more allergens in household were the risk factors associated with the incidence of persistent cough and persistent expectoration （P<0.05）. ConclusionTo 2013，2020 air pollution in Shanghai has been mitigated and prevalence of bronchial asthma and bronchitis of children has decreased. Childhood respiratory and allergic diseases are associated with indoor and outdoor environment， family medical history， and family daily habits.

Pathological insulin resistance (IR) is closely related to gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in women with GDM. Increasing studies have investigated the efficacy of IR indices, such as quantitative insulin sensitivity index, homeostasis model assessment of insulin resistance, triglyceride-glucose index and sex hormone-binding globulin, in predicting GDM and related complications in recent years. This article reviews the research progress in the above topics.

Sterols, a class of cyclopentane poly-hydrophenanthrene derivatives, are the predominant membrane constituent of eukaryotes. These substances have a variety of biological activities and have been widely used in food and pharmaceutical industries. The presence of endogenous ergosterol biosynthetic pathway in Saccharomyces cerevisiae cells make it an ideal chassis for the de novo synthesis of sterol and its derivatives. Most recently, the rational modification of organelles provides a novel strategy for the directed transportation and storage of target products and the ultimate enhanced product synthesis. This review summarizes the phenotypic responses of S. cerevisiae cells upon different physiological stimulations and the underlying molecular mechanisms. Reinforcement of sterol production through directed storage, transportation, and excretion of sterols offers a novel strategy for breaking the limitation of de novo biosynthesis of sterols in yeast.
Ergosterol ; Phytosterols ; Saccharomyces cerevisiae ; Sterols

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.

Anaphylaxis is increasingly in children, which is currently undernotified, underdiagnosed, and undertreated in China.In order to further improved the understanding and management of anaphylaxis, this issue reviews the pathogenesis, triggers and risk factors, clinical diagnosis and management of anaphylaxis, thus offers the recommedations of anaphylaxis in Chinese children based on previous published evidence-based guidelines and practice parameters.Recommendation aims to develop guiding principles for the diagnosis and management of anaphylaxis in children, and provide a framework for the development of new guidelines.

Macrophages play an important role in material-related immune responses and bone formation, but the functionality of macrophage-derived extracellular vesicles (EVs) in material-mediated bone regeneration is still unclear. Here, we evaluated intracellular communication through small extracellular vesicles (sEVs) and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen (IMC). After implantation in the bone defect area, IMC generated more neobone and recruited more mesenchymal stem cells (MSCs) than did extrafibrillarly mineralized collagen (EMC). More CD63
Biomimetics ; Bone Regeneration ; Cell Differentiation ; Collagen ; Extracellular Vesicles ; Macrophages ; Osteogenesis

Objective To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018.All subjects were separated into three groups based on antibiotics regimens over 72 hours,including meropenem 2.0 g every 8 hours,tigecycline 200 mg as initial dose and 100 mg every 12 hours,and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline.Results A total of 86 patients were finally recruited,including 14,52 and 20 patients in groups of meropenem,tigecycline and polymyxin B salvage,respectively.All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially,while 2 of them became resistant to tigecycline during treatment.The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5％,32/52) and (12/20),respectively (P＜0.01),while as no significant difference was seen in the last two groups (x2=0.014,P＞0.05).The incidences of hepatic impairment [3.8％(2/52) vs.1/20] and renal dysfunction (0 vs.1/20) between tigecycline group and polymyxin B salvage group were both comparable (P＞0.05).Conclusion The meropenem-based therapy is not recommended for CRKP-related bloodstream infections.Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours.Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.