Objective:To evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice.Methods:SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups ( n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T 0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results:Compared with C group, the MWT was significantly decreased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups ( P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight ( P>0.05), the MWT was significantly increased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group ( P<0.05). Conclusions:Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective:To investigate the current status of scientific fitness literacy (SFL) and its influencing factors among Chinese adults aged 20-59 years.Methods:Totally 63 338 adults aged 20-59 years in the status of national fitness activities in 2020 from 1 January to 31 March 2020 were selected as the subjects, and they were divided into four age groups, namely, the 20-29 age group, the 30-39 age group, the 40-49 age group and the 50-59 age group. Data were analyzed by SPSS 29.0.Comparative analyses for age, gender, urban-rural difference were carried out by applying non-parametric tests, and multiple regression models were applied to find the influencing factors of SFL.Results:The SFL score of Chinese adults aged 20-59 years was 53.40 (41.67, 63.73), and the scores of cognition, attitude, ability and skills, behavior and habits sub-dimensions were 86.11 (72.22, 100.00), 62.96 (50.62, 75.31), 27.78 (11.11, 44.44) and 33.33 (11.11, 55.56), respectively. The SFL and the four sub-dimensions were demonstrated to have higher scores for males than females, and higher scores for adults in urban area than those in rural area(all P<0.01). The multiple regression results showed that regular exercise at a fitness facility (20-29 age group: β=0.321, t=5.940, P<0.01; 30-39 age group: β=0.187, t=2.937, P<0.01; 40-49 age group: β=0.230, t=3.988, P<0.01; 50-59 age group: β=0.415, t=5.671, P<0.01) was the Chinese adults' common influence factor on SFL.Motivation, evaluation by those around them, experience from exercising, and convenience and atmosphere of exercising were the main influence factors in the 20-29 and 30-39 age groups(all P<0.05).Comfort level of fitness venue, convenience, safety, and support of fitness place were the main influence factors in adults aged 40-59 years(all P<0.05). Conclusions:Chinese adults aged 20-59 years old have high SFL awareness scores, but low overall SFL scores. Surrounding people's evaluation, experience in exercise, comfort level of fitness place, convenience, safety and fitness policy support are the influential factors of scientific fitness literacy.

Objective:To evaluate the role of spinal cord neuron Src-associated-in-mitosis-68-kDa (SAM68)-transient receptor potential vanilloid-1 channel (TRPV1) signaling pathway in diabetic neuropathic pain (DNP) in mice.Methods:Forty SPF male C57BL/6 mice, aged 8 weeks, weighing 18-22 g, were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin 0.12 mg/g, and successful DNP model was defined as decrease in the mechanical paw withdrawal threshold (MWT) of the hind limb≥50% of the baseline value. Twenty-four mice with DNP at 4 weeks after developing the model were divided into 3 groups ( n=8 each) using a simple random sampling: DNP group, SAM68 knocked down group (KD group) and virus control group (VC group). Eight diabetic mice with decrease in MWT <50% were randomly selected as non-DNP group (ND group), and 8 normal mice were randomly selected as control group (NC group). At 4 weeks after developing the diabetes mellitus model, SAM68 gene silencing virus and empty virus were injected into the lumbar enlargement of the spinal cord in KD group and VC group, respectively. MWT was measured before developing the diabetes mellitus model and at 4 and 6 weeks after developing the diabetes mellitus model. The mice were sacrificed after the end of MWT measurement at week 6 after developing the model, spinal cord tissues were collected and the expression of SAM68 and TRPV1 was detected by Western blot, and their localization in the spinal cord was observed by immunofluorescence. Results:Compared with NC and ND groups, the MWT was significantly decreased at 4 and 6 weeks after developing the model, and the expression of SAM68 and TRPV1 in spinal cord tissues was up-regulated in DNP group ( P<0.05). Compared with DNP group, the MWT was significantly increased at 6 weeks after developing the model, the expression of SAM68 and TRPV1 in spinal cord tissues was down-regulated, and no significant change was found in the parameters mentioned above in VC group ( P>0.05). SAM68 and TRPV1 were expressed in neurons in the same region of the spinal cord. Conclusions:Activation of SAM68-TRPV1 signaling pathway in spinal cord neurons is involved in the pathophysiological mechanism of DNP in mice.

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.
Humans ; Female ; Cell Proliferation ; Breast Neoplasms/drug therapy* ; Tumor Suppressor Protein p53/genetics* ; Molecular Docking Simulation

China ; History of Medicine ; Medicine/standards*