Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective:To investigate the clinical efficacy and safety of the triplet regimen of flumatinib, venetoclax (VEN) and azacitidine (AZA) for Philadelphia chromosome-positive (Ph +) mixed-phenotype acute leukemia (MPAL). Methods:The clinical data of 2 Ph + MPAL patients treated with triplet regimen of flumatinib, VEN and AZA who were admitted to the Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College in February and March 2023 were retrospectively analyzed, and the relevant literature was reviewed. Results:Patient 1 was a 56-year-old female, and patient 2 was a 59-year-old male. Both patients were diagnosed with Ph + B cell/myeloid (B/My) MPAL. After the first course of induction chemotherapy with the triplet regimen, patient 1 achieved hematological complete remission (HCR), complete cytogenetic remission (CCyR) and major molecular response (MMR), and patient 2 achieved HCR and CCyR. During the entire treatment process, the adverse reactions of two patients were mainly fever and ≥ grade 3 hematological adverse reactions, which were relieved after the use of antibiotics and intermittent infusion of blood products. When the patient achieved HCR and received consolidation treatment with the same regimen, the adverse reactions were mild. Conclusions:The triplet regimen of flumatinib, VEN and AZA is safe and effective for the treatment of Ph + MPAL, and is a new induction therapy option for such patients.

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*

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.

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 investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.

Objective:To investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.

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.