Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

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.

This article reports a patient with extensive high-pressure injection injury of the hand combined with deep chemical burn caused by high-pressure injection of industrial cement materials was diagnosed and treated in the Department of Hand Surgery, Xiaolan Hospital Affiliated to Southern Medical University in 2022. The nerves, tendons and blood vessels of the left hand were involved, and the ulnar skin of the left thumb was extensively necrosis, and a large number of extensive cement foreign bodies remained under the skin. Part of the cement was inserted into the joint capsule of the interphalangeal joint. After emergency surgical treatment, the patient was saved successfully, and the wound healed well without chemical poisoning and other related complications, which created conditions for the second stage of flap repair.

This article reports a patient with extensive high-pressure injection injury of the hand combined with deep chemical burn caused by high-pressure injection of industrial cement materials was diagnosed and treated in the Department of Hand Surgery, Xiaolan Hospital Affiliated to Southern Medical University in 2022. The nerves, tendons and blood vessels of the left hand were involved, and the ulnar skin of the left thumb was extensively necrosis, and a large number of extensive cement foreign bodies remained under the skin. Part of the cement was inserted into the joint capsule of the interphalangeal joint. After emergency surgical treatment, the patient was saved successfully, and the wound healed well without chemical poisoning and other related complications, which created conditions for the second stage of flap repair.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema. Methods: and Results: hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were div-ided into four groups: Control, Control＋MSC, SU5416 and SU5416＋MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×106 hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed. HE staining and mean linear intercepts showed that SU5416-treated rats exhibited typical emphysema while emphysematous changes in model rats after hUC-MSCs transplantation disappeared completely and were restored to normal phenotype. Furthermore, hUC-MSCs inhibited apoptosis as shown by TUNEL and Western blotting.ELISA and Western blotting showed hUC-MSCs rescued VEGF-VEGFR2-AKT pathway in emphysematous lungs. Conclusions The findings show that hUC-MSCs effectively repair the emphysema injury. This study provides the first evidence that hUC-MSCs inhibit apoptosis via rescuing VEGF- VEGFR2-AKT pathway in a rat model of emphysema.

Objective:To evaluate the clinical efficacy of extensively hydrolyzed protein formula(eHF) in very low birth weight(VLBW) infants.Methods:A prospective controlled signal-center trial was conducted in this study, the preterm infants with gestational age of 28-33 weeks and birth weight of 999-1 500 g who were hospitalized at Department of Neonatology, Zhuhai Maternal Hospital within the first 12 hours between January and December 2018, were selected.They were assigned into breast feeding group(HM) and formula feeding group according to the mothers′ disease and parents′ breastfeeding willingness.The formula feeding group was assigned into eHF group and preterm formula (PF)group according to the parents′ breastfeeding willingness.The infants discharging or dead before achieving full feeding, discharging within 28 days after birth, with congenital malformation (complex congenital heart disease, digestive system malformation, etc) and severe sepsis were rolled out. Chi- square test and One- Way ANOVA were used for statistical analysis.Prospective study was conducted among the 3 groups comparing the incidence of feeding intolerance, duration of meconium discharge, the time to regain birth weight and reach full enteral feeding, average hospital stay, incidence of necrotizing enterocolitis of newborn(NEC), cholestasis and extrauterine growth retardation(EUGR), the growth rate of head circumference, length and weight in the first 4 weeks of life, and blood biochemical indices at the first 2 weeks and 4 weeks of life. Results:A total of 102 infants were enrolled, 35 cases in the eHF group, 37 cases in the PF group and 30 cases in the HM group.Compared with the PF group [54.0%(20/37 cases)], the eHF group[22.0%(8/35 cases)] and the HM group [16.7%(5/30 cases)] had lower incidence of feeding intolerance, and the differences were statistically significant( χ2=7.366, 9.901, all P<0.05). The time to regain birth weight[(8.9±1.8) d, (9.1±1.4) d vs.(10.8±2.9) d], time for achieving full enteral feeding [(42.8±2.8) d, (42.3±3.3) vs.(45.5±3.4) d], the duration of meconium discharge [(7.2±1.8) d, (6.6±1.8) d vs.(8.7±2.1) d], and average hospital stay [(52.9±1.1) d, (52.3±1.2) d vs.(54.1±1.2) d]in the eHF group and HM group were shorter than those in PF group, and the differences were statistically significant(all P<0.05); and there was no statistically significant difference between the eHF group and the HM group(all P>0.05). There was no statistically significant difference in the incidence of incidence of NEC, cholestasis and EUGR, the growth rate of head circumfe-rence, length and weight in the first 4 weeks of life, the serum albumin, creatinine, urea nitrogen at first 2 weeks and 4 weeks of life among the 3 groups (all P>0.05). Compared with the PF group, the serum total bilirubin levels in the eHF group and the HM group were lower at 2 weeks [(109.4± 4.6) μmol/L, (110.2±1.0) μmol/L vs.(115.0±7.6) μmol/L]and 4 weeks after birth[(79.3±9.7) μmol/L, (80.0±1.7) μmol/L vs.(81.5±8.4)μmol/L], and the differences were statistically significant(all P<0.05), but no statistically significant difference was found between the eHF goup and the HM group(all P>0.05). Conclusions:For VLBW infants, eHF can reduce feeding intole-rance, promote defecation, achieve full feeding faster, promote bilirubin metabolism, shorten hospital stay, does not affect growth and development in short-term.

The Atopic march denotes the progression from atopic dermatitis (AD) to the development of other allergic disorders such as immunoglobulin (Ig) E-mediated food allergy, allergic rhinitis and asthma in later childhood. There is increasing evidence from prospective birth cohort studies that early-onset AD is a risk factor for other allergic diseases or is found in strong association with them. Animal studies now provide mechanistic insights into the pathways that may be responsible for triggering the progression from the skin barrier dysfunction seen in AD to epicutaneous sensitization, food allergy and allergic airway disorders. Recent large randomized controlled trials have demonstrated the efficacy of early interventions targeted at AD and food allergy prevention. These show great promise for research into future strategies aimed at prevention of the atopic march.
Animals ; Asthma ; Cohort Studies ; Dermatitis, Atopic* ; Early Intervention (Education) ; Food Hypersensitivity* ; Immunoglobulins ; Parturition ; Prospective Studies ; Rhinitis, Allergic ; Risk Factors ; Skin

The prevalence and patterns of food allergy are highly variable in different parts of the world. Differences in food allergy epidemiology may be attributed to a complex interplay of genetic, epigenetic, and environmental factors, suggesting that mechanisms of food allergy may differ in various global populations. Genetic polymorphisms, migration, climate, and infant feeding practices all modulate food allergy risk, and possibly also the efficacy of interventions aimed at primary prevention of food allergy development. Approaches to diagnosis, treatment, and prevention of food allergy should thus be tailored carefully to each population's unique genetic and environmental make-up. Future research in the context of food allergy prevention should focus on elucidating factors determining differential responses between populations.
Climate ; Dermatitis, Atopic ; Diagnosis ; Epidemiology ; Epigenomics ; Food Hypersensitivity* ; Genetics ; Humans ; Infant ; Polymorphism, Genetic ; Prevalence ; Primary Prevention

Objective To investigate whether soluble PD-1 overexpression in 4T1 senescence tumor cells enhances the anti-tumor effect of senescence tumor cell vaccine (STCV) against breast tumor cells in a tumor-bearing mouse model. Methods 4T1 cells were treated with interferon-γ (IFN-γ) and the expression of PD-L1 was detected by flow cytometry. CCK8 assay was used to compare the cell proliferation activity between 4T1 cells and 4T1 cells infected by a lentiviral vector of sPD-1 (4T1/sPD-1 cells), and the expressions of sPD-1 mRNA and protein in 4T1/sPD-1 cells were detected using qPCR and Western blotting. The culture supernatant of 4T1/sPD-1 cells was added in 4T1 cells pre-treated with IFN-γ, and PD-1-positive 4T1 cells were detected with flow cytometry. Senescenceβ-galactosidase staining kit was used to detect the senescent 4T1 and 4T1/sPD-1 cells following exposure to X-ray radiation and Veliparib. Balb/c mice bearing subcutaneous 4T1 tumor xenografts were treated with injections of PBS, 4T1 STCV, or 4T1/sPD-1 STCV, and tumor growth was observed. Results Stimulation with IFN-γconcentration-dependently up-regulated PD-L1 expression by as much as (84.80 ± 1.03)％ in 4T1 cells (P<0.001). sPD-1 overexpression in 4T1 cells did not significantly affect the cell proliferation. Treatment of 4T1 cells with 4T1/sPD-1 cell culture supernatant significantly increased the proportion of PD-1 + cells from (6.893 ± 0.271)％ to (55.450 ± 0.555)％ (P<0.001). X-ray irradiation combined with Veliparib caused obvious senescence in 4T1 and 4T1/sPD-1 cells. In the tumor-preventing experiment, tumor formation occurred in all the mice in PBS group;28.787％of the mice in 4T1 STCV group and 55.556％in 4T1/sPD-1 STCV group showed no tumor formation. In the tumor treatment experiment, tumor formation occurred in all the mice in PBS groups while in 4T1 STCV and 4T1/sPD-1 STCV groups, 11.111％ and 38.89％ of the mice were tumor-free during the observation period, respectively. Conclusions Senescence tumor cells vaccine has anti-tumor effect against breast cancer in mice, and sPD-1 over-expression can enhance this effect of the vaccine.