Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Imidazoles/administration & dosage* ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Metastasis ; Oximes/administration & dosage* ; Proto-Oncogene Mas ; Proto-Oncogene Proteins B-raf/genetics* ; Pyridones/administration & dosage* ; Pyrimidinones/administration & dosage*

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To investigate the prognostic value of echocardiography indicators combined with se-rum recombinant human arginase 1(ARG1)and glucose-6-phosphate dehydrogenase(G6PD)in children with sepsis.Methods A total of 116 children with sepsis admitted to the hospital from May 2022 to June 2023 were enrolled in the study as the sepsis group.According to the severity of sepsis,the children were further divided into general sepsis group(52 cases),severe sepsis group(38 cases)and septic shock group(26 cases).Ac-cording to the prognosis of the children,the children with sepsis were divided into good prognosis group(84 cases)and poor prognosis group(32 cases).A total of 116 healthy children who underwent physical examina-tion in the hospital during the same period were enrolled as the control group.The left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic volume(LV-EDV)and early diastolic mitral flow peak velocity(E)were detected by using color Doppler ultrasound.Ser-um ARG1 and G6PD levels were detected by using enzyme-linked immunosorbent assay(ELISA).The echo-cardiographic indexes and serum ARG1 and G6PD levels were compared between the sepsis group and the con-trol group,and among sepsis children with different disease severity and different prognosis.The receiver op-erating characteristic(ROC)curve was used to analyze the predictive value of echocardiographic indexes com-bined with serum ARG1 and G6PD for poor prognosis in children with sepsis.Results Compared with the control group,the sepsis group had significant reductions in LVEF,E,and G6PD(P＜0.05)and significant increases in LVEDD,LVEDV,and ARG1(P＜0.05).With the aggravation of sepsis,the levels of LVEF,E,and G6PD in children with sepsis gradually decreased(P＜0.05),while the levels of LVEDD,LVEDV,and ARG1 gradually increased(P＜0.05).Compared with the good prognosis group,the poor prognosis group had significantly lower levels of LVEF,E,and G6PD(P＜0.05)and significantly higher levels of LVEDD,LV-EDV,and ARG1(P＜0.05).ROC curve analysis showed that the AUC of echocardiographic indexes com-bined with serum ARG1 and G6PD in predicting poor prognosis of children with sepsis was 0.971,and the sensitivity and specificity were 84.4％and 83.2％,respectively.Conclusion The levels of LVEF,E,and G6PD in children with sepsis significantly decreases,and the levels of LVEDD,LVEDV,and ARG1 signifi-cantly increases.Echocardiographic parameters combined with serum ARG1 and G6PD have high predictive value for poor prognosis in children with sepsis.

Objective To explore the characteristics of apolipoprotein E(APOE)gene polymorphism in patients with Alzheimer's disease(AD)and mild cognitive impairment(MCI)due to AD,as well as its corre-lation with baseline levels of ketone bodies.Methods A total of 110 AD patients from the outpatient and neu-rology wards of the hospital from January 2020 to October 2023 were selected as the AD group,105 patients(none of whom had used anti dementia drugs)were selected as the MCI group,and 110 healthy elderly exami-nees in the physical examination center were selected as the control group.APOE gene polymorphism,and the levels of serum β-hydroxybutyrate(HB)and urine ketone bodies were measured.The distribution of APOE genotype among the three groups was analyzed,and the differences of the levels of serum HB and urine ketone bodies were compared among those carried APOE ε4 allele and those did not.Results Among the three groups,the statistical significance was found in the differences of APOE genotype and ε2,ε3,ε4 allele(P<0.05).The proportion of APOE ε4 allele carriers in the AD group and the MCI group was higher than that in the control group(P<0.05).The levels of serum βHB in the AD group and the MCI group were lower than that in the control group(P<0.05).The levels of serum βHB in those carried APOE ε4 in the AD group were significantly lower than that in the control individuals(P<0.05).There was no statistically significant differ-ence in serum βHB levels between individuals carried and not carried APOE ε4 in the three groups(P>0.05).There was no statistically significant difference in the levels of urinary ketones among the three groups(P>0.05).There was no statistically significant difference in urine ketone bodies levels between individuals carried and not carried APOE ε4 in the three groups(P>0.05).Conclusion The reduced baseline levels of serum βHB in AD patients are associated with APOE ε4 allele.

Objective To knock out cdc42 gene in zebrafish using CRISPR/Cas9 technology,and investigate the effect of cdc42 on early osteochondral development.Methods After the conservation of cdc42 gene sequence of different species was analyzed by multiple sequence alignment analysis,guide RNA of cdc42 gene was designed,and cdc42 knockout zebrafish was constructed by CRISPR/Cas9 technology.The expression pattern of cdc42 was detected by whole-mount in situ hybridization,and the chondrogenesis phenotype was observed by transgenic labeled fish line Tg(col2a1a:GFP),and vertebral mineralization was observed by alizarin red staining.Results Multiple sequence alignment analysis showed that cdc42 was highly conserved in human,mouse and zebrafish,and in situ hybridization results showed that cdc42 was expressed in a variety of tissues in the head and whole body,including mandibular cartilage.With the aid of guide RNA of cdc42,cdc42 knockout zebrafish was successfully constructed by CRISPR/Cas9 technology.The cdc42 mutants exhibited shortened body length(P＜0.01)and delayed cranial development at 3 d post fertilization,with small heads and eyes(P＜0.01),as well as delayed mandibular development.The Tg(col2a1a:GFP)zebrafish showed that the mutants presented abnormal morphology of Meckel's cartilage and ceratohyal cartilage cells,with disordered arrangement of chondrocytes and increased angle and decreased length in ceratohyal cartilage(P＜0.01).The homozygous mutants died at 10～13 d after fertilization.The results of alizarin red staining suggested delayed vertebral mineralization and reduced endochondral ossification of the mutants.Conclusion CRISPR/Cas9 technology successfully knocks out the cdc42 gene in zebrafish,resulting in delayed development of jaw cartilage,delayed mineralization of the vertebrae,and decreased endochondral ossification.