Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

OBJECTIVE: To explore clinical efficacy of congenital brachymetatarsia with immediate metatarsal lengthening. METHODS: From March 2015 to December 2020, 7 patients with brachymetatarsia were treated, including 6 females and 1 male;aged range from 18 to 30 years old;there were 5 patients with metatarsal microsomia on one foot, 2 patients with metatarsal microsomia on the first and fourth right foot, and immediate extension of metatarsal microsomia on the first and fourth right foot;two patients were short metatarsal bones of both feet. The length of short metatarsal bone, length of normal metatarsal bone, distance of short metatarsal bone and healing of bone graft were observed before and 12 months after operation. American Orthopaedic Foot and Ankle Society (AOFAS) scores were used to evaluate clinical efficacy and observe complications. RESULTS: Seven patients were followed up for 12 to 24 months. All metatarsal bones were extended to satisfactory length and bone graft were healed completely. Metatarsal length and shortening distance were improved from 3.55 to 5.90 cm and 0.77 to 1.46 cm before operation to 4.31 to 6.87 cm and 0.04 to 0.57 cm at 12 months after operation. Postoperative X-ray of the affected foot at 12 months showed bone healing was achieved between metatarsal bone and bone graft in 7 patients, and the parabolic shape of the distal metatarsal bone recovered after operation. AOFAS scores improved from 40 to 70 before operation to 88 to 95 points at 12 months after operation, and 6 patients were excellent and 1 good. CONCLUSION Immediate extension of metatarsal bone for congenital brachymetatarsia, the transplanted bone grew well during the process of bone grafting healing, the occurrence of bone nonunion was reduced, the short metatarsal bone was restored to a satisfactory length, and the toe function restored well.
Humans ; Female ; Male ; Metatarsal Bones/abnormalities* ; Adult ; Adolescent ; Young Adult ; Bone Lengthening/methods* ; Foot Deformities, Congenital/surgery*

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Aim To investigate the role of FKBP38 in inhibiting apoptosis in a rotenone-induced Parkinson's disease(PD)cell model. Methods In vivo experiments:MPTP-induced PD in vivo models were constructed,and the expressions of α-synuclein,TH and FKBP38 in brains of PD mice were detected. In vitro experiments:Dopaminergic neuron MN9D cells were stimulated with rotenone to construct an in vitro model of PD; Western blot was used to detect the expression levels of α-synuclein,TH,Tom20 and FKBP38 in PD in vitro model; FKBP38 lentivirus was transferred into MN9D cells to construct stable overexpression and FKBP38 knockdown cell lines; CCK-8 assay was used to detect the cell viability of FKBP38 overexpression and knockdown cells stimulated by rotenone; Western blot was used to detect anti-apoptotic protein Bcl-2 and apoptosis protein in PD cell model expression levels of Bax. Results The expression level of FKBP38 was significantly down-regulated in both in vitro and in vivo models of PD(P<0.01). Knockdown of FKBP38 aggravated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05),while overexpression of FKBP38 significantly ameliorated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05). Western blot results showed that overexpression of FKBP38 could significantly up-regulate the expression level of anti-apoptotic protein Bcl-2 and increase the ratio of Bcl-2/Bax in PD dopaminergic neurons(P<0.05). Conclusion In the PD cell model regulation of FKBP38 can improve the apoptosis of dopaminergic neurons.

Depressive disorder is manifested as emotional and physical abnormality. Theoretically, the governor vessel is distributed along the spine, related to the brain and communicated with five zang and six fu organs. It is the key meridian for understanding the various symptoms of depressive disorder. Depressive disorder is caused by dysfunction, stagnation or emptiness of the governor vessel, resulting in malnutrition of the brain. In clinical diagnosis and treatment, based on the theory of the governor vessel, the etiology and pathogenesis are analyzed in the patients with depressive disorder. In order to achieve harmonizing mutually the mental and physical conditions, acupuncture is delivered to adjust the spirit and physical state, moving cupping is to regulate the governor vessel, tuina manipulation is to promote meridians and collaterals and physical exercise is to coordinate the body and the spirit.
Humans ; Acupuncture Therapy/methods* ; Meridians ; Acupuncture ; Brain ; Depressive Disorder ; Acupuncture Points

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.
Humans ; Wound Healing ; Health Facilities ; Delivery of Health Care ; China ; Wounds and Injuries/therapy*

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Apoptosis ; Benzothiazoles ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Paclitaxel/therapeutic use* ; Phenylurea Compounds ; RNA, Messenger ; STAT5 Transcription Factor/pharmacology* ; Signal Transduction ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To explore the clinical application of lockedge suspension combined with three steel wires vertical fixation in comminuted fracture of inferior pole of patella. METHODS: From August 2016 to May 2019, 23 patients with comminuted fracture of the lower pole of the patella, including 14 males and 9 females, were treated with lockedge suspension combined with three steel wires vertical fixation. The age ranged from 34 to 68 (55.0±1.2) years. One year after operation, the pain and function were evaluated by pain visual analogue scale(VAS) and knee flexion and extension range of motion, and the clinical efficacy was evaluated by Lysholm knee score standard. RESULTS: All 23 patients were followed up for 12 to 14, with a mean of(13.0±0.5) months. One patient had skin irritation by the tail of the steel wire, and the rest had no postoperative complications such as incision infection, internal fixation loosening and fracture displacement. The fractures of 23 patients were healed, and the healing time was 10 to 14 weeks with a mean of(12.0±1.1) weeks. The VAS score decreased from 7.96±0.93 before operation to 0.83±0.65 one year after operation. The range of knee flexion and extension activities increased from(20.30±8.69) ° before operation to 1 year after operation(127.39±6.55) °. Lysholm knee score increased from 18.48±4.00 before operation to 96.09±4.91 one year after operation(P<0.05). CONCLUSION The treatment of comminuted fracture of the lower pole of patella by lockedge suspension combined with three steel wires vertical fixation has reliable fixation and high fracture healing rate. It can meet the requirements of rapid rehabilitation and functional exercise, and the early clinical effect is satisfactory.
Adult ; Aged ; Bone Wires ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Fractures, Comminuted/surgery* ; Humans ; Male ; Middle Aged ; Patella/surgery* ; Steel ; Treatment Outcome