摘要 目的 近年来多项研究提示瘦素可能在帕金森病（PD）患者神经元细胞中发挥保护作用，但相关结果尚不一致，因此本研究采用Meta分析方法系统评估瘦素在PD患者中的作用。方法 在PubMed、Embase、ISI Web of Science和中国国家知识基础设施（CNKI）数据库中系统性检索2020年3月底前的文献研究。为了评估总体效果，采用固定效应模型计算合并效应量、标准化均差（SMD）和95%CI。随后进行了亚组分析、敏感性分析和发表偏倚分析，以揭示纳入研究的稳定性和可信度。结果 本研究纳入了7项研究，包括167例帕金森病患者和141名健康对照者。本研究发现，帕金森病患者的血清瘦素水平显著低于健康对照者（SMD=-0.328，95%CI -0.560~-0.096，P=0.006）。亚组分析显示，白种人PD患者的血清瘦素水平较低（SMD=-0.301，95%CI -0.566~-0.036，P=0.026），而亚洲患者的血清瘦素水平差异无统计学意义（SMD=-0.414，95%CI -0.891~0.063，P=0.089）。敏感性分析显示总体效应量的稳定性。通过观察漏斗图，未发现明显的不对称，Begg检验也未发现显著的发表偏倚。结论 本Meta分析结果表明PD患者血清瘦素水平较健康人群降低，提示血清瘦素可能参与PD的病理过程，其具体机制尚待进一步研究阐明。 Abstract Objective Many studies in recent years have shown that leptin may exert a protective effect on neurons in patients with Parkinson disease（PD），but related research findings remain inconsistent. Therefore， this article systematically reviews the role of leptin in PD patients through a meta-analysis. Methods PubMed，Embase，ISI Web of Science， and CNKI were searched for related articles published up to March 2020. In order to assess the overall effect， the fixed effects model was used to calculate pooled effect size， standardized mean difference （SMD）， and 95% confidence interval（CI）. Subgroup analysis， sensitivity analysis， and publication bias analysis were performed to assess the stability and reliability of the studies included in the meta-analysis. Results A total of 7 studies were included in the meta-analysis according to strict inclusion criteria， involving 167 PD patients and 141 healthy controls. The results showed that the PD patients had a significantly lower serum level of leptin than the healthy controls （SMD=-0.328，95%CI -0.560 to -0.096， P=0.006）. The subgroup analysis showed that Caucasian PD patients had a relatively low serum level of leptin （SMD=-0.301， 95%CI -0.566 to -0.036，P=0.026）， while there was no significant difference in the serum level of leptin among Asian patients （SMD=-0.414， 95%CI -0.891 to 0.063， P=0.089）.The sensitivity analysis showed the stability of overall effect size. The funnel plots showed no significant asymmetry， and no obvious publication bias was observed by the Begg test. Conclusion This meta-analysis shows that PD patients have a lower serum level of leptin than the healthy population， suggesting that serum leptin might be involved in the pathological process of PD， and further studies are needed to clarify the specific mechanism.
Leptin ; Adipokines

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

OBJECTIVE To investigate the effect of neferine(NEF)on mitophagy in Parkinson's disease(PD)cells by regulating the adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/UNC-51-like kinase 1(ULK1)signaling pathway,and explore the mechanism of this drug to improve PD.METHODS SH-SY5Y cells were treated with 100 μmol/L 1-methyl-4-phenylpyridinium ion(MPP+)for 24 h to construct a PD cell model.PD model cells were divided into model group(PD group),NEF low-,medium-and high-concentration groups(NEF-L,NEF-M,NEF-H group,2.5,5.0,10.0 μmol/L),and high concentration of NEF+AMPK inhibitor group(NEF-H+Compound C group,10.0 μmol/L NEF+50μmol/L Compound C).The cells treated without MPP+and NEF were used as the control group.The ultrastructure of the cells in each group was observed;the amount of autophagosomes,survival rate,apoptosis rate,mitochondrial membrane potential,and the protein expressions of Caspase-3,microtubule-associated protein 1 light chain 3(LC3)and Beclin-1,as well as the phosphorylation levels of mTOR,AMPK and ULK1 were detected.RESULTS Compared with PD group,the amount of autophagosomes in NEF-L,NEF-M and NEF-H groups was increased,and membrane potential was increased;survival rate,LC3-Ⅱ/LC3-Ⅰ,protein expression of Beclin-1,and protein phosphorylation levels of AMPK and ULK1 were significantly increased or up-regulated;the apoptotic rate,protein expressions of Caspase-3 and p62,and protein phosphorylation level of mTOR were significantly decreased or down-regulated,and the above improvements were in a dose-dependent manner(P＜0.05).Compound C could significantly reverse the above improvement effect of high concentration of NEF(P＜0.05).CONCLUSIONS NEF can promote mitophagy and inhibit apoptosis of PD model cells by up-regulating protein phosphorylation levels of AMPK and ULK1,and down-regulating protein phosphorylation level of mTOR,thus playing a protective role in nerve cells.

Background Agitated behaviour in male patients with schizophrenia can lead to serious consequences for the individual and the society.Non-invasive drug delivery may help to rapidly control agitation and improve the overall patient satisfaction,but there are limited studies on the efficacy of olanzapine oral soluble film for the treatment of agitated behaviour in patients with schizophrenia.Objective To compare the efficacy and safety profile of olanzapine oral soluble film versus intramuscular haloperidol against agitated behaviour in male patients with schizophrenia,so as to provide a reference for the treatment of agitated behaviour.Methods From May 2022 to July 2023,a consecutive sample of schizophrenic patients(n=44)with agitated behaviour who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)were recruited in the male psychiatric closed ward of the Third People's Hospital of Fuyang.Patients were assigned into two groups using the random number table method,each with 22 cases.Study group was treated with olanzapine oral soluble film 10 mg/d,while control group was given intramuscular haloperidol 8 mg/d.The severity of agitated behaviour was determined using Positive and Negative Syndrome Scale-Excited Component(PANSS-EC)and Agitation Calmness Evaluation Scale(ACES)at the baseline and after 6 h of drug administration.The treatment response rate was calculated based on the reduction of PANSS-EC score,and the drug side effects were assessed using Rating Scale for Extrapyramidal Side Effects(RSESE)and Barnes Akathisia Rating Scale(BARS)after 6 h of drug administration.Results After 6 h of drug administration,no statistical difference was reported in PANSS-EC score and ACES score between two groups(F=0.039,0.082,P>0.05),and the treatment response rate yielded no statistical difference between two groups(χ2=0.419,P=0.517),while study group reported a lower incidence rate of adverse reactions compared with control group,with statistically significant difference(P=0.031).BARS scores noted no statistical significant difference between two groups(t=0.587,P=0.561),whereas study group scored lower on RSES compared to control group,with a statistical difference(t=-7.367,P<0.01).Conclusion In the treatment of agitation in male patients with schizophrenia,the efficacy of olanzapine oral soluble film is comparable to that of intramuscular haloperidol,while the safety profile of the former is superior to that of the latter.

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

OBJECTIVES: Rhinoplasty is one of the most common cosmetic surgeries in China. Septal extension grafts (SEG) have been widely used in rhinoplasty, but there are few reports on SEG derived from ear cartilage. This study aims to explore the effectiveness and stability of auricular cartilage nasal SEG transplantation in Chinese rhinoplasty. METHODS: A retrospective analysis of 35 rhinoplasty patients admitted from September 2019 to March 2022 has been conducted. Among them, 29 patients underwent rhinoplasty for the first time and 6 patients underwent rhinoplasty with the age of 18-32 (average 22.4) years old. The postoperative follow-up was 3-28 (average 18.5) months. The improvement of the nose shape was observed. The changes of the nose tip angle, nasolabial angle, and nasofrontal angle were compared between before and after the operation, and the complications were recorded. RESULTS: All patients who underwent rhinoplasty with a septal extension grafts constructed from the concha cavity and concha cartilage showed significant improvement in nasal contour. The preoperative nasal tip angle, nasolabial angle, and nasofrontal angle were significantly improved compared with 3 months after operation (all P<0.001), and there was no significant difference between 3 months and 14 months after operation (all P>0.05). The appearance of nasal cavity was satisfactory in 32 patients after operation. Columella deviation occurred in 2 patients and 1 patient complained of downward rotation of the nasal tip, which was satisfied after readjustment of the graft. CONCLUSIONS The simplified SEG derived from auricular cartilage can provide stable support for the nasal tip, the nasal shape is natural after operation, and minimal trauma of unilateral auricle cartilage transplantation remains.
Humans ; Young Adult ; Adult ; Rhinoplasty ; Ear Cartilage/transplantation* ; Retrospective Studies ; Nasal Septum/transplantation* ; Plastic Surgery Procedures

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated. Here, using conditional-knockout mice, we found that astrocytic HMGB1 depletion decreased morbidity, delayed the onset time, and reduced the disease score and demyelination of EAE. Meanwhile, there were fewer immune cells, especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice, accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo. In vitro, HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells (BMECs) through TLR4 or RAGE. Taken together, our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; HMGB1 Protein/metabolism* ; Endothelial Cells/metabolism* ; Mice, Inbred C57BL ; Mice, Knockout ; Blood-Brain Barrier/metabolism*

Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.

This study was aimed to explore the effect of Periplaneta Americana against alcohol-induced liver injury in mice, in order to provide a theoretical basis for the industrial production of P. Americana. Kunming mice were randomly divided into six groups, which were the normal group, model group, positive group, high-, middle-, low-dose of P. Americana groups. Intragastric administration of Tiopronin Enteric-coated Tablets 100 mg·kg-1 was given to the positive group. Intragastric administrations of whole powder of medicine were given to the high-, middle-, low-dose groups with the dosage of 6.667, 3.333, 1.667 g·kg-1, respectively. The drugs were given daily for 10 con-secutive days. After 3h of the 10th day drug administration, intragastric administration of distilled water was given to the normal group, while 14mL·kg-1 of 56℃ Red Star Liquor was given to other groups. No food was given but water for 12h. Blood was collected from the orbit. The ALT, AST and GGT in blood serum of mice were measured. The liver was dissected and liver coefficient was calculated. Histopathological examination was given on liver tissues. The results showed that compared with the normal group, the level of ALT, AST in blood serum of the model group had obvious enhanced (P< 0.01), the level of GGT had obvious enhanced (P< 0.05). Compared with the model group, the level of GGT, AST of the high-, middle-dose group had obvious enhanced (P< 0.05), the level of ALT activity had obvious enhanced (P< 0.01). There were severe liver histopathological damages in mice of the high-, middle-, low-dose group. It was concluded that P. Americana had some side effects in the treatment of alcohol-induced liver injury.