Background::Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods::In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1·h -1, which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1·h -1, whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1·h -1, which could be adjusted to 0.30-4.00 mg·kg -1·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. Results::Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. Conclusions::ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration::ClinicalTrials.gov, NCT04147416.

BACKGROUND: Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. METHODS: CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. RESULTS: Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. CONCLUSION Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Objective: To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. Methods: HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). Results: Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×10⁶ RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). Conclusions There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.

The 2019 Academic Annual Meeting of the Chinese Burn Association, sponsored by the Chinese Medical Association and the Chinese Burn Association, was successfully held in Zhuhai, Guangdong province, from November 6th to 9th, 2019. The theme of this conference was " One China, One Standard--Data Standardization and Construction of National Burn Data Platform" . A total of 2 305 submissions and 1 749 e-posters were received, and 1 097 registered representatives, nearly 2 000 representatives from 9 countries and regions attended the meeting. Focusing on the theme of this conference, a variety of novel forms were adopted such as teaching contest of young surgeons, multi-disciplinary discussion, workshop, and surgery live broadcast on hot issues in key areas of burns. Besides, with the focus on humanistic care and innovation, a multi-disciplinary discussion was warmly conducted. The 2020 academic annual conference is scheduled to be held in Nanchang, China.

OBJECTIVE: To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. METHODS: HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). RESULTS: Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×10⁶ RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). CONCLUSIONS There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.
Apoptosis ; Humans ; Kidney ; Lipopolysaccharides ; Mitochondrial Dynamics/drug effects* ; Protective Agents/pharmacology* ; Pyruvates/pharmacology*

Background:PM(aerodynamic diameter ≤ 2.5 μm) is a dominant and ubiquitous air pollutant that has become a global concern as PMexposure has been linked to many adverse health effects including cardiovascular and pulmonary diseases. Emerging evidence supports a correlation between increased air PMlevels and skin disorders although reports on the underlying pathophysiological mechanisms are limited. Oxidative stress is the most common mechanism of PM-induced adverse health effects. This study aimed to investigate PM-induced oxidative damage and apoptosis in immortalized human keratinocyte (HaCaT) cells.

Methods:HaCaT cells were exposed to 0, 25, 50, 100, or 200 μg/ml PMfor 24 h. Reactive oxygen species (ROS) generation, lipid peroxidation products, antioxidant activity, DNA damage, apoptotic protein expression, and cell apoptosis were measured.

Results:PMexposure (0-200 μg/ml) for 24 h resulted in increased ROS levels (arbitrary unit: 201.00 ± 19.28, 264.50 ± 17.91, 305.05 ± 19.57, 427.95 ± 18.32, and 436.70 ± 17.77) and malondialdehyde production (0.54 ± 0.05 nmol/mg prot, 0.61 ± 0.06 nmol/mg prot, 0.68 ± 0.05 nmol/mg prot, 0.70 ± 0.05 nmol/mg prot, and 0.76 ± 0.05 nmol/mg prot), diminished superoxide dismutase activity (6.47 ± 0.28 NU/mg prot, 5.97 ± 0.30 NU/mg prot, 5.15 ± 0.42 NU/mg prot, 4.08 ± 0.20 NU/mg prot, and 3.76 ± 0.37 NU/mg prot), and increased DNA damage and apoptosis in a dose-dependent manner in HaCaT cells. Moreover, cytochrome-c, caspase-3, and caspase-9 expression also increased proportionately with PMdosing.

Conclusion:PMmight elicit oxidative stress and mitochondria-dependent apoptosis that likely manifests as skin irritation and damage.

OBJECTIVETo investigate the features of intelligence development, facial expression recognition ability, and the association between them in children with autism spectrum disorder (ASD).

METHODSA total of 27 ASD children aged 6-16 years (ASD group, full intelligence quotient >70) and age- and gender-matched normally developed children (control group) were enrolled. Wechsler Intelligence Scale for Children Fourth Edition and Chinese Static Facial Expression Photos were used for intelligence evaluation and facial expression recognition test.

RESULTSCompared with the control group, the ASD group had significantly lower scores of full intelligence quotient, verbal comprehension index, perceptual reasoning index (PRI), processing speed index（PSI), and working memory index (WMI) (P<0.05). The ASD group also had a significantly lower overall accuracy rate of facial expression recognition and significantly lower accuracy rates of the recognition of happy, angry, sad, and frightened expressions than the control group (P<0.05). In the ASD group, the overall accuracy rate of facial expression recognition and the accuracy rates of the recognition of happy and frightened expressions were positively correlated with PRI (r=0.415, 0.455, and 0.393 respectively; P<0.05). The accuracy rate of the recognition of angry expression was positively correlated with WMI (r=0.397; P<0.05).

CONCLUSIONSASD children have delayed intelligence development compared with normally developed children and impaired expression recognition ability. Perceptual reasoning and working memory abilities are positively correlated with expression recognition ability, which suggests that insufficient perceptual reasoning and working memory abilities may be important factors affecting facial expression recognition ability in ASD children.

Adolescent ; Autism Spectrum Disorder ; psychology ; Child ; Child Development ; Facial Expression ; Female ; Humans ; Intelligence ; Male

OBJECTIVETo introduce different surgical treatment for gyncomastia at different grades.

METHODS37 cases with gynecomastia were divided into three grades as: grade I with fat as main tissue, grade II with proliferated fibro-gland as main tissue, grade III with big and ptosis breasts and sagging skin. Different surgical methods were chosen according to the different grades of gyncomastia. These include liposuction, subareolar fibroglandular tissue removing, combined technique of the two methods, and breasts resection with free transplantation of nipple-areola complex.

RESULTSAll patients were satisfied for the appearance of post-operative flat male chest. Complications, such as scar, numbness of nipple and areola were acceptable for them.

CONCLUSIONSDifferent surgical methods should be chosen for the gynecomastia at different grades. It can improve both the physical and psychological problems for patients.

Adolescent ; Gynecomastia ; classification ; surgery ; Humans ; Lipectomy ; Male ; Mammaplasty ; methods ; Nipples ; transplantation ; Retrospective Studies

OBJECTIVETo investigate the value of Compound Xuanju Capsule in the treatment of type-III prostatitis-related sexual dysfunction.

METHODSWe randomly divided 90 type-III prostatitis patients with sexual dysfunction diagnosed by NIH clinical criteria into an experiment group and a control group to be treated with Compound Xuanju Capsule and antibiotics, respectively. We analyzed the therapeutic results based on the scores on chronic prostatitis symptom index (CPSI), prostatitis-related sexual function index (PSFI ) and self-rating anxiety scale (SAS), and compared them between the two groups and with the baseline data.

RESULTSThe degree of prostatitis-related sexual dysfunction was not correlated with that of prostatitis symptoms. Prostatitis symptoms and sexual function were significantly improved in the experiment group than in the control (P < 0.05), and the SAS score was markedly lower in the former than in the latter (P < 0.05).

CONCLUSIONCompound Xuanju Capsule can not only alleviate the symptoms of type-III prostatitis, but also improve its related sexual dysfunction and anxiety.

Adolescent ; Adult ; Capsules ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Prostatitis ; complications ; drug therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the prevalence of psychiatric disorders in a representative sample of primary and middle school students in Hunan Province.

METHODSA total of 9 495 children aged 5-17 years from Hunan urban and rural schools were enrolled by a cluster sampling and a two-phase design. The students' psychiatric status was assessed using the Investigation Screening Inventory for Child Mental Disorder and a semi-structured interview designed based on the DSM-IV criteria.

RESULTSThe overall prevalence of psychiatric disorders was 16.22%. Attention-deficit and disruptive behavior disorders were the commonest in the diagnostic categories of psychiatric disorders (10.69%). Regarding specific disorders, the most prevalent was attention-deficit/hyperactivity disorder (5.95%). Psychiatric disorders were more prevalent in boys than in girls (20.49% vs 11.16%; p<0.01). The prevalence of attention-deficit and disruptive behavior disorders in boys was higher than in girls (14.76% vs 5.87%; p<0.01). The prevalence of psychiatric disorders in middle school students (12-17 years) was significantly higher than in primary students (5-11 years) (18.38% vs 14.64%; p<0.01). There were no significant differences in the prevalence of psychiatric disorders between urban and rural students.

CONCLUSIONSPsychiatric disorders are common among primary and middle school students in Hunan Province. The prevalence of this disorder in boys is higher than in girls. The middle school students have higher prevalence than primary students.

Adolescent ; Age Factors ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Male ; Mental Disorders ; epidemiology ; Prevalence ; Sex Factors