Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances. Here, we will review and discuss the well-established and emerging astroglial biology and functions, with emphasis on their potential as therapeutic targets for CNS injury, including traumatic and ischemic injury. This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
Astrocytes/drug effects* ; Humans ; Animals ; Central Nervous System/pathology* ; Central Nervous System Diseases/physiopathology*

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.

Objective:To analyze the necessity of anastomosis of the cutaneous nerve by comparing anterolateral femoral flaps with versus without anastomosis of the anterolateral femoral cutaneous nerve in the repair of extremity soft tissue defects.Methods:A retrospective analysis was made of the clinical data of 30 patients with extremity soft tissue defects who had been admitted to Department of Orthopedics, The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University School of Medicine from September 2019 to March 2022. The patients were assigned into 2 groups according to whether the anterolateral femoral cutaneous nerve was anastomosed or not in the repair of extremity soft tissue defects using anterolateral femoral flaps. In the anastomosis groups of 14 cases, there were 7 males and 7 females, with an age of (46.4±15.2) years and a flap size of (22.4±7.3) cm×(8.5±1.3) cm. In the non-anastomosis group of 16 cases, there were 11 males and 5 females, with an age of (39.9±15.8) years and a flap size of (23.0±6.4) cm×(9.0±2.1) cm. The 2 groups were compared in terms of flap survival, Semmes-Weinstein recovery degree and area of monofilament tactile sensation, and time periods for temperature sensation and two-point discrimination.Results:There was no statistically significant difference between the 2 groups in the preoperative general data, showing they were comparable ( P>0.05). All the flaps survived completely without vascular crisis. In the anastomosis group, the time periods required for Semmes-Weinstein recovery of monofilament tactile sensation to the areas of 20.0%, 50.0%, and 80.0% [(2.5±0.7) months, (6.7±1.1) months, and (11.0±1.2) months] were significantly shorter than those in the non-anastomosis group [(3.6±1.3) months, (8.6±1.4) months, and (15.0±2.2) months], the recovery area at the last follow-up [100.0% (100.0%, 100.0%)] was significantly larger than that in the non-anastomosis group [84.6% (81.7%, 89.9%)], and the time period for recovery of temperature sensation [(3.9±0.7) months] significantly shorter than that in the non-anastomosis group [(6.1±1.1) months] (all P<0.05). The time for recovery of two-point discrimination in the 14 patients in the anastomosis group was (10.4±1.7) months while only 7 of the 16 patients in the non-anastomosis group recovered two-point discrimination after (14.7±1.4) months, showing a significant difference between the 2 groups ( P<0.05). Conclusion:In the repair of extremity soft tissue defects using anterolateral femoral flaps, compared with no anastomosis of the cutaneous nerve, anastomosis of the anterolateral femoral cutaneous nerve may ensure more or less the sensory recovery of the flaps.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Objective: This study aims to investigate the epidemiological distribution of HFMD and quantify the association of temperature with the incidence of children’s HFMD in Nanjing, China. Methods: Daily counts of HFMD in children under 5 years and daily meteorological variables during 2011-2016 were obtained. Descriptive statistics were used to describe the epidemiological characteristics and distributed lag non linear model (DLNM) was used to assess the associations of temperature on HFMD cases. Results: A total of 104 977 HFMD cases aged 0-5 years were reported in Nanjing during the study period and the male to female sex ratio was 1.49∶1. The average annual incidence was 213.5 per 100 000. A bimodal seasonal pattern was observed and the south and west were found to be the high incidence areas in the city. Of these laboratory confirmed enteroviruses positive cases, 32.5% cases were positive for EV-A71 infections, 29.1% cases were positive for CV-A16 infections and 38.4% cases were positive of other enteroviruses infections. The temperature HFMD relationships were non linear and showed obvious lag effects. The cumulative relative risk presented as an approximately inverted U shape over 14 days and peaked at 25.7 ℃ with value of 2.71(95%CI=1.93-3.81). Subgroup analyses revealed that males and children aged <1 year were more vulnerable to temperature variations. Conclusion Epidemiological characteristics of HFMD among children aged 0-5 years old in Nanjing presented temporal and regional distribution. The temperature has significant impact on children’s HFMD occurrence.

Objective: To understand the status quo and differences of the rights and interests of primary medical staff in a community, and to provide targeted suggestions for improving the rights of such staff. Methods: From October to November 2018, a questionnaire survey was conducted on all the medical staff of 8 community health service centers in a district of Shanghai, and 562 valid samples were obtained. Results: The primary medical staff had the highest demands for " pay rise" (4.783±0.598), " paid vacation" (4.569±0.873)and " additional reserve fund" (4.553±0.963); the lowest demands were placed on " education-based promotion" (3.797±1.382), " refresher training" (3.801±1.314), and " opinion feedback mechanism" (4.018±1.223). At the same time, the rights and interests of these staff in different occupational categories were significantly different(P<0.05)in " daily reimbursement" , " housing subsidy" , " refresher training" and " opinion feedback mechanism" . Conclusions The salary demands of the primary medical staff are the most obvious, and there are differences in the demands of medical staff in different occupational categories. It is suggested to establish a more reasonable salary system and pay attention to the differentiated appeals of different medical personnel.

Objective To evaluate the effects of different concentrations of desflurane on the electrophysiological stability of hearts in female patients.Methods Forty female patients,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 20-50 yr,weighing 45-77 kg,scheduled for elective surgery with general anesthesia,were divided into 2 groups (n =20 each) using a random number table method:0.6 MAC group (group D1) and 1.3 MAC group (group D2).The intravenous access was opened after admission to the operating room,midazolam 0.1 mg/kg,vecuronium 0.1 mg/kg,fentanyl 3 μg/kg and etomidate 0.3 mg/kg were injected intravenously,and mechanical ventilation was performed after tracheal intubation.The concentrations of desflurane reached 0.6 and 1.3 MAC in D1 and D2 groups,respectively.Twelve-lead electrocardiograms were collected before anesthesia induction (T1),at 5 min after intubation (T2) and at 20 min after reaching the set concentration of desflurane (T3).The QT interval and Tpe interval were measured,the QTc interval,Tp-e/QT ratio and index of cardiac electrophysiological balance were calculated,and the development of arrhythmia was also observed.Results The QT interval and QTc interval were significantly longer,and the Tp-e/QT ratio was lower at T3 than at T1,2 in two groups (P＜ 0.05).There was no significant difference in QT interval,Tp-e/QT ratio or index of cardiac electrophysiological balance at each time point between two groups (P＞0.05).No arrhythmia was found in neither group.Conclusion The clinical concentration of desflurane affects the electrophysiological stability of hearts to some extent in female patients without causing arrhythmia.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.