Aim To investigate the central mechanism by which dexmedetomidine(DEX)alleviated pain sensitization and anxiety-like behaviors in mice caused by nicotine withdrawal stress.Methods A mouse model of nicotine withdrawal was established,and DEX was administered to detect its effects on the behaviors of nicotine-withdrawn mice.The von Frey mechanical pain test was used to measure the pain threshold of mice,and the open-field test was used to detect the anxiety-like behaviors of mice.Immunofluorescence staining was performed to detect the changes in neurons in the anterior cingulate cortex(ACC)and locus coer-uleus(LC)brain regions of nicotine-withdrawn mice.Anterograde and retrograde tracing viruses were used to detect the projection connection between LC and ACC.Chemogenetic methods were used to regulate the activi-ty of LC neurons.Fiber photometry was used to detect the release of norepinephrine and the activity of neu-rons in the ACC.Results Nicotine-withdrawn mice exhibited pain sensitization and anxiety-like behaviors.The activities of neurons in the LC and ACC of nico-tine-withdrawn mice increased.A functional projection connection was found in the LC-ACC neural circuit.Activating the LC-ACC neural circuit induced pain hy-persensitivity and anxiety-like behaviors in mice.DEX alleviated the pain hypersensitivity and anxiety-like be-haviors caused by nicotine withdrawal through the LC-ACC neural circuit.Conclusion DEX acts on the LC-ACC neural circuit,inhibits the release of norepi-nephrine and the activity of neurons in the ACC,and alleviates the pain sensitization and anxiety-like behav-iors induced by nicotine withdrawal.

Aim To investigate the central mechanism by which dexmedetomidine(DEX)alleviated pain sensitization and anxiety-like behaviors in mice caused by nicotine withdrawal stress.Methods A mouse model of nicotine withdrawal was established,and DEX was administered to detect its effects on the behaviors of nicotine-withdrawn mice.The von Frey mechanical pain test was used to measure the pain threshold of mice,and the open-field test was used to detect the anxiety-like behaviors of mice.Immunofluorescence staining was performed to detect the changes in neurons in the anterior cingulate cortex(ACC)and locus coer-uleus(LC)brain regions of nicotine-withdrawn mice.Anterograde and retrograde tracing viruses were used to detect the projection connection between LC and ACC.Chemogenetic methods were used to regulate the activi-ty of LC neurons.Fiber photometry was used to detect the release of norepinephrine and the activity of neu-rons in the ACC.Results Nicotine-withdrawn mice exhibited pain sensitization and anxiety-like behaviors.The activities of neurons in the LC and ACC of nico-tine-withdrawn mice increased.A functional projection connection was found in the LC-ACC neural circuit.Activating the LC-ACC neural circuit induced pain hy-persensitivity and anxiety-like behaviors in mice.DEX alleviated the pain hypersensitivity and anxiety-like be-haviors caused by nicotine withdrawal through the LC-ACC neural circuit.Conclusion DEX acts on the LC-ACC neural circuit,inhibits the release of norepi-nephrine and the activity of neurons in the ACC,and alleviates the pain sensitization and anxiety-like behav-iors induced by nicotine withdrawal.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To explore the influencing factors of microcirculation dysfunction in patients with anterior wall acute myocardial infarction(AMI)and to establish a relevant prediction model.Methods A total of 130 patients with anterior wall AMI,whose microcirculation function was assessed by caIMR after receiving percutaneous coronary intervention(PCI)at Shanghai Sixth People's Hospital of China from January 2017 to September 2020,were enrolled in this study.The patients were divided into abnormal microcirculation resistance group(n=52)and normal microcirculation resistance group(n=78).The clinical data were compared between the two groups.The regression analysis was used to analyze the influencing factors of microcirculation dysfunction.Results In the abnormal microcirculation resistance group the contrast agent consumption,the onset-to-operation time,the Gensini total score and the LAD Gensini score were(121.92±31.37)mL,(10.51±5.12)min,(97.91±31.77)points and(69.36±13.15)points respectively,which were significantly higher than(109.03±28.2)mL,(4.94±2.94)min,(81.05±35.22)points and(54.45±23.48)points respectively in the normal microcirculation resistance group,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).A prediction model covering interventional strategies was established,and its accuracy was higher than that of a conventional model,its AUC compared with the conventional model was 0.91 to 0.87,indicating that this model could well predict the risk of microcirculation dysfunction in patients with AMI after receiving PCI.Conclusion This prediction model can promptly identify high-risk microcirculation dysfunction patients with anterior wall AMI after receiving PCI.

Superoxide dismutase (SOD) is a key enzyme that scavenge superoxide anion free radical (O₂^·-) in vivo, and plays an important role in plant growth and development and stress. In this study, according to the genome and transcriptome data of Salvia miltiorrhizae, 9 SOD genes were identified and the expression patterns of SOD family genes were further analyzed, including 5 Cu/Zn-SOD, 2 Fe-SOD and 2 Mn-SOD. On the basis of proteomic analysis, combined with transcriptome data, one full-length cDNA of Mn-SOD gene, namely SmMSD2 was cloned from Salvia miltiorrhizae. The results of amino acid sequence alignment and phylogenetic analysis showed that SmMSD2 protein belongs to the manganese superoxide dismutase (Mn-SOD) subfamily, and SmMSD2 protein shares high sequence identity with the Mn-SOD proteins of various plants that all contain a C-terminal conserved metal-binding domain "DVWEHAYY". The prokaryotic expression vector pMAL-c2X-SmMSD2 was constructed and transformed into E. coli BL21 expressing strain, and the target recombinant protein was successfully induced and its enzymatic properties were analyzed. Spatiotemporal expression analysis showed that SmMSD2 gene was expressed in all tissues, indicating that SmMSD2 gene was constitutively expressed at a stable level. Real-time quantitative PCR indicated that drought (15% PEG6000), abscisic acid (ABA) and indole-3-acetic acid (IAA) could induce the expression of SmMSD2 gene, suggesting that SmMSD2 may be involved in the response of Salvia miltiorrhizae to abiotic stress such as drought, as well as the signaling pathways of phytohormone ABA and IAA. These results lay the foundation for further elucidating the involvement of superoxide dismutase in the stress response and accumulation of active components of Salvia miltiorrhiza.

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective:To investigate the alteration of right ventricular function after catheter ablation in patients with persistent atrial fibrillation(PAF) and concomitant heart failure with preserved ejection fraction (HFpEF).Methods:The prospective observational study was performed in patients with HFpEF-PAF and undergoing first-time radiofrequency ablation procedures in the First Affiliated Hospital of Nanjing University between May to December 2019. Right ventricular functional parameters were measured before and 5 days, 1, 3, 6 and 12 months after the ablation by transthoracic echocardiography, respectively, including the right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion(TAPSE), tricuspid annular diameter (TVAD), tricuspid annular peak systolic speed(TDI-S′) and longitudinal strain of right ventricular free wall (RVFLS). Meanwhile, routine ECG and Holter recordings were performed at each follow-up time point.Results:In this study, atrial fibrillation (AF) recurrence occurred in 4 patients at the 3rd month after ablation, and 7 patients failed to follow up due to the Covid-19. Finally, 19 patients were followed up for the evaluation of cardiac function after catheter ablation. Compared with pre-ablation, right ventricular structural and functional paramters(RVFAC, TAPSE, TVAD, TDI-S′, RVFLS) improved significantly at all stages of follow-up( all P<0.05). Patients with atrial fibrillation recurrence had lower RVFLS and TDI-S′ at the baseline( P=0.039, P=0.019). Conclusions:Right ventricular function could improve in HFpEF-PAF patients who maintain sinus rhythm after radiofrequency ablation.

Objective:To investigate the standardized construction of critical care departments in different cities and counties of Guizhou province to promote the homogenization development of critical care medicine in Guizhou Province.Methods:Using research methods such as field investigation and data collection, the public hospitals of 88 counties and urban areas in 9 prefectures and cities of Guizhou province were divided into five routes: southeast, northeast, northwest, southwest, and Guiyang. To design the survey form for the standardized construction of ICU, the e-form was sent to the director of ICU or his/her designated personnel by email or wechat 2-3 days in advance. Check the authenticity of data item by item on site, and leave the hospital after checking the receipt form.Results:From April to July 2021, the survey and research data collection was completed for 146 public hospitals (excluding provincial hospitals) with intensive care departments in 88 counties and cities of 9 dizhou cities in Guizhou Province, including 24 Grade-Ⅲ Level A hospitals. 122 Grade-Ⅱ and above hospitals (including 8 Grade-Ⅲ Level B hospitals, 11 Grade-Ⅲ comprehensive hospitals, 97 Level-Ⅱ A hospitals, 3 Level-Ⅱ B hospitals, and 3 Level-Ⅱ comprehensive hospitals). 146 public hospitals have a total of 80 983 beds and 104 017 open beds. The department of Critical Care has 2 035 beds. The ratio of actual beds in ICU to total beds in hospital was 2.51%. From 1999 to 2010, 18 (12.33%) established departments, and from 2011 to 2021, 128 (87.67%) established departments. The total area of the discipline is 113 355.48 m 2, with an average bed area of 55.70 m 2. There were 97 hospitals with 1.5-2.0 m bed spacing, accounting for 66.44%, and 49 hospitals with 2.1- > 2.5 m spacing, accounting for 33.56%. The number of negative pressure wards: 1 in each of 43 hospitals, accounting for 29.45%; 103 hospitals did not have, accounting for 70.55%. The number of single rooms: 288 in 140 hospitals, accounting for 95.89%; 6 hospitals did not have, accounting for 4.11%. Central oxygen supply: 138 hospitals have (94.52%); 8 hospitals did not have, accounting for 5.48%. Natural ventilation: in 129 hospitals with 88.36%; 17 hospitals did not have, accounting for 11.64%. Specialized ICU construction: 66 hospitals, accounting for 45.21%; none in 80 hospitals, accounting for 54.79%. There are 3 712 doctors and nurses in 146 public hospitals. The total number of doctors was 1 041, and the ratio of doctors to beds was 0.51∶1. The total number of nurses was 2 675, and the ratio of nurses to beds was 1.31∶1. Conclusions:All 88 counties and districts in 9 prefectures and cities of Guizhou province have established intensive care medicine departments. The standardization of the discipline construction has been significantly improved. Lack of talents is still an important factor restricting the rapid development of the discipline.

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin^®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin^®. BAT1706 and Avastin^® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin^® are highly similar in terms of in vitro functional activities.