Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To explore the mechanism of methyltransferase METTL3 in premature ovarian failure(POF)using a POF mouse model,providing a theoretical basis for the pathological research and clinical treatment of POF.Methods C57BL/6 female mice aged 6 to 8 weeks were selected for the study.The experimental group consisted of mice with a premature ovarian failure(POF)model established using the D-galactose metabolic method,while the control group comprised normal mice subjected to the same intervention with an equal volume of physiological saline.The levels of sex hormones were measured using ELISA,and histopathological changes in ovarian tissue were observed through HE staining to verify the successful establishment of the POF mouse model and to explore the correlation between METTL3 and POF at the tissue level.Additionally,stable transgenic mouse granulosa cell lines with METTL3 overexpression and knockdown were constructed at the cellular level.Cell proliferation and apoptosis were assessed using CCK-8 and FITC/PI dual staining methods to clarify the regulatory role of METTL3 in granulosa cell apoptosis and its impact on the occurrence of POF.Results The POF mouse model was successfully established.TUNEL staining revealed a significant increase in apoptotic granulosa cells in the ovarian tissue of the POF group(P＜0.05),which also exhibited high expression of METTL3.In cellular experiments,stable transcriptional cell lines of mouse granulosa cells with METTL3 overexpression and knockdown were successfully constructed.Upregulation of METTL3 expression promoted granulosa cell apoptosis and inhibited their proliferation(P＜0.05).Conclusion METTL3 participates in the development of POF by promoting granulosa cell apoptosis.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To analyze the clinical characteristics and the antimicrobial resistance of respiratory tract infection in children in Baoshan City,guide clinicians to rationally apply antibiotics,and improve the success rate of treatment.Methods Retrospective analysis of the distribution characteristics and drug sensitivity results of 1039 strains of pathogens detected in pediatric inpatients of hospitals from 2019 to 2022 was conducted.Results The main pathogens causing the respiratory infections in children in Baoshan area were Streptococcus pneumoniae,Escherichia coli,Staphylococcus aureus,Haemophilus influenzae,Klebsiella pneumoniae and Pseudomonas aeruginosa.Analysis of the drug sensitivity results of pathogenic bacteria with a detected quantity greater than 80 revealed that Streptococcus pneumoniae had a high resistance rate to erythromycin,clindamycin,and compound sulfamethoxazole.The resistance rates of penicillin,ceftriaxone,cefotaxime,and meropenem were P<0.05,and the difference was statistically significan.Methicillin-resistant Staphylococcus aureus(MRSA)was11.1%;CTX/CRO-R-ECO,CTX/CRO-R-KPN,CR-ECO and CR-KPN were lower than the 2021 ISPED level;The P.aeruginosa drug resistance rate and H.influenzae's ampicillin and ampicillin/sulbactam were higher than the 2021 ISPED level.Conclusion The treatment of respiratory tract infections in pediatric patients faces great challenges.The non-standard use of empirical medication has led to the emergence of multidrug-resistant bacteria,and the selection of anti infection treatment drugs is limited.Therefore,it is imperative to grasp the epidemic characteristics and drug resistance of pathogenic bacteria in the local area.

Objective:To explore the clinical effect of free fibular great toe flap in reconstruction of digit-tip defect with only anastomosis of artery.Methods:From February 2022 to January 2023, a total of 8 patients with digit-tip defects received reconstruction surgery using free flap of fibular great toe with anastomosis of artery only in the Department of Hand Surgery, Shunde Heping Surgical Hospital. The patients were 5 males and 3 females, with an average age of 33 (14-55) years old. Two defected digit-tips were of thumbs, 3 of index fingers, 2 of middle fingers and 1 of little finger. The digit-tip defects were 1.5 cm×0.5 cm-2.0 cm×1.2 cm in size. During the surgery, a perforator flap of fibular great toe with fibular plantar digital artery and a branch of digital nerve was harvested. And the artery and nerve carried by the flap were anastomosed to the digital artery arch and nerve of the recipient site. No reflux vein was included in the free flap due to the small size of flap. The donor sites were directly closed. Postoperative anti-infection, anti-coagulation, and anti-vasospasm were offered. Scheduled postoperative follow-ups were conducted at outpatient clinics after surgery.Results:All flaps survived smoothly without any vascular compromise. All patients were included in the follow-up with an average of 7.1 (5-13) months. At the final follow-up, the appearances of the digit-tips were full and beautiful, with recovered finger print and good stability of flaps, as well as normal sweating. All flaps had good sensation recovery, with TPD at 6.0 mm to 7.5 mm and at 6.7 mm in average. There was no significant difference in skin temperature between the donor sites and the healthy sides. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 7 patients were rated as excellent and 1 as good.Conclusion:The clinical effect is excellent for the free flap of fibular great toe with anastomosis of artery only in the reconstruction of digit-tip defect. It not only has satisfactory reconstruction but also restores the appearance and function of the flap donor site. Worth promoting and applying in clinical practice.

N6-methyladenine(m6A)modification is involved in a variety of biological processes and dynamically regulates RNA stability.When m6A modification is changed,it affects the development of follicles,granulosa cell proliferation and oocyte development,and participates in the occurrence and development of benign ovaria-related diseases,such as polycystic ovary syndrome,premature ovarian dysfunction,and endometriosis,resulting in decreased female fertility.This article reviews the role and research progress of m6A modification in benign ovaria-related diseases,aiming to provide new diagnosis and treatment ideas for subsequent research on improving fertility.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.
Animals ; Mice ; Mycobacterium tuberculosis ; Antigens, Bacterial ; Immunization ; Nanoparticles ; Vaccines, Subunit ; Mice, Inbred BALB C

Objective:To evaluated the options in selection of surgical procedures for treatment of the patients suffering from diabetic feet with chronic refractory wounds.Methods:From January 2020 to June 2021, 23 patients with diabetic feet complicated with refractory wounds were treated in Department of Hand Surgery, Shunde Heping Surgical Hospital. The patients were 15 males and 8 females, aged 51-86 years old and with an average age of 65 years old. All the patients had Type-II diabetes for over 5 - 22 years. Average blood glucose of the patients was found at 15.6 mmol/L on admission. Free anterolateral thigh perforator flaps (ALTPF) were used for reconstruction of the wound of diabetic feet in 19 patients, 2 patients received vascular bypass surgery and 2 had amputations. Regular outpatient follow-up were conduct on all patients after surgery.Results:Follow-up time lasted for 8 to 30 months, 12 months in average. At the last follow-up, the donor and recipient sites healed well in the 19 patients who received flap reconstruction, without an infection, necrosis and wound recurrence. Pains were significantly relieved after the surgery in the 2 patients who received vascular bypass surgery, and wounds all healed well after symptomatic treatment and dressing change without recurrence of wounds at the last follow-up. Average Maryland score of foot function was 84 for the patients who had limb salvage, and 2 patients were in excellent and 19 in good at the last follow-up. The 2 patients who had amputation successfully survived through the perioperative period, and the wounds healed well at the last follow-up.Conclusion:The treatment is complicated in the patient suffering from diabetic foot with chronic refractory wounds due to factors such as advanced age, co-existing and complicated underlying diseases together with the complex wounds. Most patients can achieve good prognosis in wound treatment of free flap transfer or vascular bypass surgery. However, a limb salvage is recommended with caution for the patients who have severe infections and dry gangrene.