Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

The update of multi-omics technology is a key means to promote the rapid development of accurate health model in the whole life cycle.It can formulate dynamic and accurate nursing measures and provide massive data information from the perspective of nursing biology of health and disease.At present,clinical nursing research faces many challenges such as insufficient application and transformation ability of multi-omics technology.This paper introduces the multi-omics technology,reviews the application status of multi-omics technology in cancer nursing,maternal and child nursing,chronic metabolic disease nursing and symptom management,and puts forward the cross integration and prospect of multi-omics technology and nursing research,so as to strengthen the information mining ability of nurses at different levels of health and disease,and provide an important basis for accelerating the clinical transformation of precision nursing.

Objective:To investigate the differences in programmed death-ligand 1 (PD-L1) expression and immune cell infiltration characteristics in different molecular subtypes of endometrial cancer.Methods:A retrospective case series study was conducted. Ninety primary treated EC patients who underwent surgery without preoperative neoadjuvant therapy at the Second Hospital of Tianjin Medical University from November 2016 to May 2022 were collected. The surgical paraffin-embedded tissues were selected, and the molecular subtypes of endometrial cancer were classified according to 2020 World Health Organization (WHO) molecular subtypes using POLE gene Sanger sequencing and immunohistochemical staining. The expression of PD-L1, CD3, CD4, CD8, CD68, and CD20 proteins were detected by immunohistochemistry. Stained slides were digitally scanned for quantitative analysis of PD-L1 and immune cell infiltration density. The PD-L1-related scores were evaluated, including tumor cell score (TCS, the percentage of PD-L1 positive tumor cells among total tumor cells ≥1% was TCS positive, <1% was TCS negative), immune cell score (ICS, the percentage of PD-L1 positive tumor-associated lymphocytes and macrophages among total tumor-associated lymphocytes and macrophages ≥1% was ICS positive, <1% was ICS negative) and combined positive score [CPS, PD-L1 positive stained cells (including tumor cells, lymphocytes and macrophages)/total number of viable tumor cells ×100 ≥ 1 was CPS positive, < 1 was CPS negative]. Clinicopathological characteristics, PD-L1 scores and immune cell infiltration densities among different molecular subtypes were analyzed. Kaplan-Meier method was used to plot disease-free survival (DFS) curves for molecular subtypes, PD-L1 scores and immune cell infiltration densities, with subgroup comparisons using log-rank test. Cox proportional hazards models were used for univariate and multivariate analyses of poor DFS in endometrial cancer patients.Results:The median age of 90 patients was 58 years old (range: 33-72 years old); endometrioid carcinoma was present in 78 cases (86.7%), and non-endometrioid carcinoma was present in 12 cases (13.3%). Molecular subtyping identified POLE-mutated subtype in 6 cases (6.7%), mismatch repair deficient (MMRd) subtype in 23 cases (25.6%), p53 abnormal subtype in 14 cases (15.6%), and non-specific molecular profile (NSMP) subtype in 47 cases (52.2%). Significant differences were observed among the 4 molecular subtypes in International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, morphological subtype, tertiary lymphoid structures, estrogen receptor expression, and progesterone receptor expression (all P < 0.05). Among the 90 cases, 18 cases (20.0%) were positive for TCS, 31 cases (34.4%) were positive for ICS, and 39 cases (43.3%) were positive for CPS. Significant differences were found among the 4 molecular subtypes in PD-L1 + cell density, distribution of patients with ICS positivity, and distribution of patients with CPS positivity (all P < 0.01), but not in distribution of patients with TCS positivity ( P = 0.090); compared to NSMP subtype, the proportions of ICS-positive patients in POLE-mutated and MMRd subtypes were higher, the proportion of CPS-positive patients and PD-L1 + cell density in MMRd and p53 abnormal subtypes were higher, and the differences were statistically significant (all P < 0.05). Significant differences in immune cell densities were observed among the 4 molecular subtypes (all P < 0.01); compared to NSMP subtype, POLE-mutated, MMRd and p53 abnormal subtypes had higher densities of CD3 + and CD8 + cells, MMRd subtype had higher CD4 + cell density, and POLE-mutated and MMRd subtypes had higher CD68 + and CD20 + cell densities (all P < 0.05). The median follow-up was 43 months (range: 7-75 months). Among the molecular subtypes, p53 abnormal patients had the worst DFS, and POLE-mutated patients had the best DFS, and the difference in DFS among the 4 subtypes was statistically significant ( P = 0.046). Grouping according to the median density of immune cells in the entire group, patients with high CD8 + cell density (45 cases) had better DFS than those with low density (45 cases) ( P = 0.010), PD-L1 ICS-positive patients had worse DFS than negative patients ( P = 0.019), and NSMP subtype patients with high CD4 + cell density (24 cases) had better DFS than those with low density (23 cases) ( P < 0.001). There was no statistically significant difference in DFS among patients grouping with other PD-L1 scoring modes and other immune cell infiltration density (all P > 0.05). Cox regression analysis indicated that high CD8 + cell density ( HR = 0.335, 95% CI: 0.113-0.990, P = 0.048) was an independent protective factor for poor DFS in endometrial cancer patients, and high CD4 + cell density was an independent protective factor for poor DFS in NSMP subtype patients ( HR = 0.035, 95% CI: 0.003-0.345, P = 0.004). Conclusions:There are significant differences in PD-L1 expression and immune cell infiltration density among the different molecular subtypes of endometrial cancer, which are correlated with the prognosis of patients, and may provide reference for the selection of immunotherapy strategies and prognosis judgment.

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Female ; Humans ; Computational Biology ; East Asian People ; Genetic Counseling ; Genomics ; Mutation ; Obesity, Morbid/genetics* ; Child, Preschool ; Pediatric Obesity/genetics*

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

OBJECTIVE: To summarize the effectiveness of Kirschner wire buckling combined with bone fixation in the treatment of metacarpal avulsion fracture. METHODS: The clinical data of 35 patients of metacarpal avulsion fracture admitted between March 2017 and June 2022 were retrospectively analyzed. There were 22 males and 13 females; the age ranged from 20 to 55 years, with an average of 31.6 years. There were 17 cases of the second metacarpal avulsion fracture, 6 cases of the fourth metacarpal avulsion fracture, and 12 cases of the fifth metacarpal avulsion fracture. The causes of injury included 21 cases of strangulation, 8 cases of sprain, and 6 cases of sports injury. X-ray film examination showed that the size of the avulsion fracture of metacarpal bone ranged from 0.30 cm×0.20 cm to 0.55 cm×0.45 cm. The total active motion (TAM) of the injured finger before operation was (154.00±17.38)°. The time from injury to operation was 3-10 days, with an average of 5.8 days. Follow-up regularly after operation, X-ray film and CT examination were performed to evaluate fracture healing and TAM of injured finger was measured. The finger function was evaluated by the trial standard of upper limb function evaluation of Hand Surgery Society of Chinese Medical Association. RESULTS: All the incisions healed by first intention. All 35 patients were followed up 9-36 months, with an average of 28 months. All metacarpal avulsion fractures achieved bony healing, and the healing time was 4-6 weeks, with an average of 4.8 weeks. The metacarpophalangeal joint of the patient was stable, without stiffness, and the flexion and extension activities were good. At last follow-up, the TAM of the injured finger reached (261.88±6.23)°, which was significantly different from that before operation ( t=-35.351, P<0.001). The finger function was evaluated according to the trial standard of upper limb function evaluation of the Society of Hand Surgery of Chinese Medical Association, and 33 cases were excellent and 2 cases were good, with an excellent and good rate of 100%. CONCLUSION The treatment of metacarpal avulsion fracture with Kirschner wire buckling combined with bone fixation has the advantages of less trauma, firm fixation, and less interference to the soft tissue around metacarpophalangeal joints, which is a good alternative method for the metacarpal avulsion fracture.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Fractures, Avulsion/surgery* ; Fracture Fixation, Internal/methods* ; Metacarpal Bones/injuries* ; Bone Wires ; Retrospective Studies ; Treatment Outcome ; Fractures, Bone/surgery* ; Hand Injuries

Objective:To observe the surgical method and clinical efficacy of applying calf tissue flap combined with artificial bone of antibiotics loaded calcium sulphate in treatment of tibia osteomyelitis.Methods:From July 2018 to January 2021, calf tissue flaps combined with artificial bone of antibiotics loaded calcium sulphate (or mixed with iliac bone) were applied to treat 16 cases with tibia osteomyelitis in the Department of Hand and Microsurgery of Baoji Third Hospital. There were 10 males and 6 females, aged 15 to 64 years old, with a mean age of 41 years old. For the 5 cases with acute osteomyelitis caused by wound infection, local dressing changes and drainage or VSD wound management were applied after debridement, together with primary systemic anti-infection treatment. After the acute infection period had been under control and stabilised, the wounds were then thoroughly exposed and cavities were filled and covered with the surgical reconstruction procedure with antibiotics-loaded artificial bone of calcium sulphate in combination with calf tissue flaps. For the 11 cases with chronic and hypotoxicity osteomyelitis, calf tissue flaps combined with antibiotics-blended artificial bone of calcium sulphate were applied to fill the cavity and cover the wound in phase I surgical reconstruction after thorough debridement. For the 7 cases with large bone defects or larger cavities after debridement, a mixed bone grafts of antibiotics-loaded artificial bone of calcium sulphate and autologous iliac bone were employed, with muscle flaps or myocutaneous flaps for an embedding repair. Sizes of the tissue flaps were 2.0 cm×3.5 cm to 12.0 cm×23.0 cm. Clinical outcomes were evaluated through follow-ups at outpatient clinic. The therapeutic effect was evaluated by the method described by McKee et al.Results:Except for 1 case of distal necrosis of tissue flap and survived after dressing change, the other tissue flap survived successfully. Postoperative follow-ups lasted for 12 to 40(mean 18) months. All the osteomyelitis were successfully cured, except 1 that had recurrence of osteomyelitis 1 year later, and treated with antibiotics-loaded artificial bone of calcium sulphate combined with autologous iliac bone implants after thorough debridement, and then healed well. The shape and texture of flaps were good. Protective sensations were restored to vary levels after 6 months. The calf regained weight-bearing and walking functions at 1 year after surgery. According to McKee et al., the therapeutic effect was evaluated: 11 cases were cured, 4 cases were improved, and 1 case relapsed, with an effective rate of 93.8%.Conclusion:Application of calf tissue flap combined with antibiotics-loaded artificial bone of calcium sulphate in the treatment of tibia osteomyelitis has a high cure rate and remarkable efficacy. It can significantly reduce the number of surgeries and shorten the course of disease.

Objective:To investigate the application of 3.0T multiparametric magnetic resonance imaging (Mp-MRI) prostate imaging-reporting and data system (PI-RADS) V2.1 score combined with prostate-specific antigen density (PSAD) in the diagnosis of prostate cancer (PCa).Methods:The clinical data of 82 patients with suspected PCa who were admitted to Nantong Second People's Hospital from May 2017 to Octorber 2021 were retrospectively analyzed. The 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level and pathological diagnosis were obtained from all patients. The 3.0T Mp-MRI PI-RADS V2.1 score and its distribution as well as serum PSAD level between patients with pathologically diagnosed PCa and patients with prostatic hyperplasia (BPH) were compared. The diagnostic efficiency of 3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level alone and in combination for PCa was analyzed using receiver operating characteristic (ROC) curve, with pathological results as the gold standard.Results:Pathological diagnosis showed that there were 43 cases (52.44%) of PCa and 39 cases (47.56%) of BPH. There was a statistical difference in the distribution of 3.0T Mp-MRI PI-RADS V2.1 score between PCa and BPH patients ( Z = 32.25, P<0.001). The 3.0T Mp-MRI PI-RADS V2.1 score of PCa patients was higher than that of BPH patients [(4.29±0.25) points vs. (2.24±0.11) points, P < 0.001], the serum PSAD level was higher than that of BPH patients [(0.49±0.15) ng·ml -1·cm -3 vs. (0.27±0.08) ng·ml -1·cm -3, P < 0.001]. The ROC curve analysis showed that area under the curve of 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level alone and both together for the diagnosis of PCa were 0.766 (95% CI 0.659-0.852, P < 0.001), 0.793 (95% CI 0.689- 0.874, P < 0.001) and 0.816 (95% CI 0.715-0.893, P < 0.001). Conclusions:3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level are both elevated in PCa patients. They have certain values in the diagnosis of PCa, and the combination of the two has higher diagnostic efficiency.

Objective:To evaluate the efficacy of a calf tissue flap combined with antibiotic-loaded calcium sulfate (artificial bone or mixed iliac bone graft) in the treatment of foot and ankle osteomyelitis.Methods:A retrospective study was conducted to analyze the 11 cases of foot and ankle osteomyelitis which had been treated at Department of Hand and Microsurgery, The Third Hospital of Baoji from October 2018 to October 2021. There were 8 males and 3 females, aged (42.3±23.7) years. The chronic hypotoxic osteomyelitis was repaired and reconstructed after thorough debridement at one stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound. The acute infected trauma was repaired and reconstructed after thorough debridement at the second stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound only after the acute infection was controlled by local dressing, drainage or negative pressure therapy and systemic anti-infection treatment at the primary stage. The flap size ranged from 3.5 cm × 2.0 cm to 12.0 cm × 6.0 cm. Four cases were treated by a peroneal artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a flap with peroneal artery perforator and peroneal nerve trophic vessel combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a posterior tibial artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, and one by a peroneus longus muscle flap combined with antibiotic-loaded calcium sulfate artificial bone. Postoperatively, the flap survival, bone union time, ankle function and complications were observed; the therapeutic efficacy was evaluated by comparing infection control indexes at the final follow-up [clinical manifestations like local redness, swelling, pain, ulceration, and exudation, and white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and calcitoninogen (PCT)].Results:All the flaps survived except for one which developed necrosis at the distal 1/3 of the flap but responded to dressing change. All the patients were followed up for (22.6±11.5) months. The 6-month follow-up revealed that all the flaps were fine in shape and texture. Re-examinations showed that WBC, CRP, ESR and PCT were normal or close to normal, the local skin was free of redness, swelling or ulceration, and protective sensation was restored to varying degrees. X-ray at (12.1±2.3) months showed that lesions disappeared, bony union was achieved, the ankle joint regained basic flexion and extension, and the affected limb also regained weight-bearing and walking functions in all the patients but one whose X-ray at 18 months showed poor bony union but no other symptoms or signs.Conclusion:In the treatment of foot and ankle osteomyelitis, a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone can promote bone healing and restore the function of the foot and ankle because it not only fills the cavity and covers the wound but also effectively controls the infection.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.