Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

BACKGROUND:Studies have demonstrated that postmenopausal osteoporosis is related to female reproductive characteristics and exercise diets,but few studies have demonstrated whether female reproductive characteristics and exercise diets have an effect on vitamin D in postmenopausal women. OBJECTIVE:To investigate the relationship of vitamin D levels with female reproductive characteristics and exercise diets and their influencing factors in postmenopausal women in Beijing. METHODS:Totally 727 postmenopausal women with an age range of 46-75 years old who received on-site questionnaires in 17 communities of Beijing from September 2017 to May 2018 were selected as the study subjects,and the questionnaires included the subjects'basic information and history of menstruation,menopause,pregnancy,and exercise diet.An electrochemiluminescence immunoassay analyzer and its auxiliary reagents were used to determine 25-(OH)D levels.Bone mineral density and T values of the lumbar spine(L1-L4,whole)and both hips(femoral neck,whole)were determined using a dual-energy X-ray bone mineral density detector.The correlation of vitamin D with reproductive characteristics and exercise diet was observed,as well as the influencing factors of vitamin D were analyzed. RESULTS AND CONCLUSION:There were 136 cases(18.7%)in the vitamin D normal group,389 cases(53.5%)in the vitamin D insufficient group,and 202 cases(27.8%)in the vitamin D deficient group.The mean vitamin D level was(15.60±5.85)ng/mL.With the increase of vitamin D level,the bone mineral density value and T value of different parts of the body also increased.Vitamin D level was positively correlated with age at menarche,days of menstrual duration,stage of menopause,activity,diet type,and dietary preference(P<0.05);was negatively correlated with menstrual cycle,age at menopause,and number of childbearing(P<0.05);and had no correlation with age at first conception and number of pregnancies(P>0.05).The results of multifactorial ordered Logistic regression analyses showed that there was a positive correlation between the frequency of drinking dairy products and vitamin D level(P<0.05),and dairy products were a protective factor for vitamin D level.To conclude,vitamin D levels are generally insufficient and bone mineral density values are generally low in postmenopausal women in Beijing.Vitamin D levels are correlated with some reproductive characteristics and exercise diets,and drinking dairy products is a protective factor.Therefore,it is possible to intervene in the dietary situation of postmenopausal women by means of health education about osteoporosis and by increasing vitamin D levels in order to increase bone density values and reduce the prevalence of osteoporosis in the postmenopausal period.

OBJECTIVE: To compare the clinical efficacy and complication rates of staged open reduction internal fixation (ORIF) and external fixation combined with limited internal fixation (EFLIF) in the treatment of high-energy Pilon fractures. METHODS: A retrospective selection was conducted on 78 patients diagnosed with high-energy tibial Pilon fractures who received treatment between January 2021 and October 2023. These patients were categorized into the staged ORIF group and the EFLIF group according to their respective treatment protocols. The staged ORIF group comprised 48 patients, including 29 males and 19 females, aged from 33 to 53 years old with a mean age of (43.25±4.67) years old. The time from injury to treatment averaged (6.54±2.21) hours. All patients received staged ORIF treatment. The EFLIF Group consisted of 30 patients, including 18 males and 12 females, aged from 36 to 54 years old with a mean age of (43.37±3.24) years old. The time from injury to treatment averaged (6.87±1.96) hours. All patients received EFLIF treatment. The recovery of ankle joint function, fracture reduction quality, fracture healing time, and surgical-related indicators between two groups were observed and compared six months after surgery. Additionally, the postoperative complications of the two groups were recorded. RESULTS: Both groups of patients were followed up and the duration ranged from 6 to 12 months, with an average of (8.97±1.26) months. At 6-month postoperative follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score in the ORIF group was (83.15±20.93), which did not show a statistically significant difference compared to the EFLIF group (81.88±20.67), P>0.05. The excellent and good rate of fracture reduction in the staged ORIF group was 33.33% (16/48), which did not show a statistically significant difference compared to the EFLIF group (30.00%, 9/30), P>0.05. The hospitalization duration and fracture healing time in the staged ORIF group were (16.57±1.25) days and (12.14±1.15) weeks, respectively. When compared to the EFLIF group, which demonstrated a hospitalization duration of (15.97±2.16 ) days and a fracture healing time of (12.36±1.17) weeks, no statistically significant differences were observed (P>0.05). The intraoperative blood loss in the staged ORIF group was (76.54±11.65) ml, which was significantly higher than that in the EFLIF group (70.15±10.29) ml, and the difference was statistically significant (P<0.05). The incidence of superficial tissue infection was 2.08%(1/48), which was significantly lower than that observed in the EFLIF group at 16.67% (5/30), and this difference was statistically significant (P<0.05). CONCLUSION Both staged ORIF and EFLIF were effective treatment options for high-energy closed Pilon fractures of the tibia. However, regarding the prevention of superficial tissue infection, staged ORIF demonstrates superior risk control compared to EFLIF.
Humans ; Male ; Female ; Middle Aged ; Adult ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; External Fixators ; Open Fracture Reduction/methods* ; Treatment Outcome

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.

Objective To investigate the correlation between muscle strength level and bone mineral density and bone metabolism indexes in postmenopausal women in Beijing.Methods Postmenopausal women who were investi-gated by on-site questionnaires and followed by bone mineral density examination in Beijing from September 2017 to May 2018 were recruited as study subjects.They were divided into early menopausal group,middle menopausal group,late menopausal group,and twilight menopausal group according to the years of menopause.Changes in grip strength,5 times sit-to-stand test(FTSST)with bone mineral density(BMD)and bone metabolism indexes were observed in the four groups and their correlations were analyzed.Results A total of 815 cases of postmenopausal women were included.At different menopausal stages,muscle strength was all found to decrease with the increase of menopausal years(P＜0.05),there was non-significance of different bone metabolism indexes among the four groups(P＞0.05);Femoral neck and lumbar spine BMD decreased with the increase of menopausal years(P＜0.05).Maximum grip strength was positively correlated with both femoral neck and lumbar spine BMD(R=0.158,P＜0.05;R=0.130,P＜0.05).There was no correlation between muscle strength and bone metabo-lism indexes(P＜0.05).Conclusions Different bone metabolism indexes are not associated with muscle strength in menopausal women.Maximum grip strength is positively correlated with bone mineral density,which can be used as an auxiliary screening tool for osteoporosis(OP)in women.The FTSST suggests that the lower limb muscle strength of menopausal women decreases with age,which can be used as one of the indicators for predicting the risk of falls in menopausal women.

Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.

Objective:To investigated the relationship between magnetic resonance imaging(MRI)parameters and the molecular pathology of primary central nervous system lymphoma(PCNSL).Methods:We retrospectively analyzed 26 patients from The First Affiliated Hospital of Harbin Medical University between January 2020 and June 2023 classified into germinal center B-cell like(GCB)and non-germinal center B-cell like(non-GCB)groups based on cell origin,into Ki-67≥75%and<75%groups based on the Ki-67 index,into BCL-2+and BCL-2-groups based on BCL-2 expression,and into responsive and non-responsive groups based on their response to MAP+Bruton's tyrosine kinase inhib-itor(BTKi)treatment.We extracted and compared first-order parameters between the groups,including mean value,standard deviation,variance,coefficient of variation,skewness,kurtosis,and entropy from baseline MRI images.Results:Four parameters(variance,kurtosis,skewness,and coefficient of variation)showed no significant differences between groups.However,three parameters(mean,standard devi-ation,and entropy)significantly differed between the groups based on Ki-67 and BCL-2 expression.For the Ki-67 index,the three parameters'areas under the curve(AUC)were 0.731,0.831,and 0.913,respectively.For BCL-2 expression,the mean and standard deviation AUCs were 0.889 and 0.938,respectively.In addition,the mean and entropy parameters significantly differed between the groups categorized by cell origin and treatment responsiveness(P<0.05).Multi-parameter joint analysis demonstrated greater identification accuracy compared to util-izing individual quantitative parameters from texture analysis.Conclusions:The mean,standard deviation,and entropy MRI parameters can help predict Ki-67 and BCL-2 expression in patients with PCNSL and have evaluative functions for treatment.They are beneficial for preoper-ative non-invasive assessment of tumor malignancy,providing vidence for prognosis and treatment planning.

Objective To investigate the effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.

AIM:In order to quantitatively exam-ine the improvement of insulin sensitivity(IS)in pa-tients with type 2 diabetes mellitus(T2DM)when exendin-4-lgG4-Fc(E4F4)was given for 12 weeks,the present study was conducted to establish E4F4 population oral glucose minimal models based on the meal tolerance test(MTT)data of E4F4 pre-and post-dosing,and to analyze whether low-dose(2.7 mg)administration for 12 weeks significantly improved insulin sensitivity in patients with T2DM.METHODS:Blood glucose and insulin concentra-tions were collected among 16 subjects in the study who completed MTT before or after dosing.Nonlinear mixed-effects model construction for the population oral glucose minimal models was per-formed using NONMEN 7.2 software using pre-and post-dosing data,respectively.The insulin sensitivi-ty parameters obtained from the models before and after the administration of the drug were sta-tistically analyzed using GraphPad Prism 8.0.RE-SULTS:Nonparametric test of IS before and after dosing showed statistical difference(P=0.02),and insulin sensitivity after dosing was significantly higher than the baseline value before dosing.CON-CLUSION:12 weeks of low-dose E4F4 treatment in patients with type 2 diabetes mellitus resulted in an improvement in insulin sensitivity.This study provides a pharmacodynamic basis for the efficacy of this novel biologic.