In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

A family carrying a homozygous variant of DNAJB2 gene C.91C>T (p.His31Tyr) with distal hereditary motor neuropathy (dHMN) associated with early-onset Parkinson′s disease was reported. The patient presented with distal limb weakness and atrophy at the early stage of the disease, and developed Parkinson′s symptoms more than 10 years later. Neuroelectrophysiological examination suggested motor and sensory axonal involvement. This mutation site had not been reported and was considered to be a neogenic mutagenicity of dHMN, excluding other mutations that can cause early-onset Parkinson′s disease.

Pancreatic cancer (PC) is a malignant digestive tract tumor with poor prognosis. Most of patients with PC are insensitive to traditional strategies of chemotherapy, targeted therapy and immunotherapy. PC with microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) is rare in clinic, which has distinctive clinicopathological characteristics and better prognosis from conventional PC. Reasonable acquisition of pancreatic tumor biopsy and accurate assessment of MSI-H/dMMR status are helpful for accurate diagnosis of such patients. Individualized treatment strategy based on immunotherapy can significantly improve the prognosis of patients with MSI-H/dMMR PC. Based on relevant literatures of domestic and foreign, the authors discuss the current status and research hotspots of diagnosis and treatment for MSI-H/dMMR PC.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Neurexin-3α, discovered in 2016, is a new type of autoimmune encephalitis antibody. Anti-neurexin-3α antibody-associated encephalitis is generally associated with prodromal symptoms or mood changes, having main clinical manifestations as seizures, memory disorders, confusion or loss of consciousness, central ventilation insufficiency, abnormal behavior, and speech disorders. This paper reviews the relevant research progress at home and abroad about pathogenesis, diagnosis and differential diagnosis, treatment and prognosis of anti-neurexin-3α antibody-associated encephalitis, so as to expand the understanding of clinicians for this disease.

Objective To systematically evaluate the correlation between vitamin D deficiency in early pregnancy and the outcome of preterm birth.Method PubMed,Embase,the Cochrane Library,Web of Science,Ebsco,CBM,CNKI and Wanfang Data databases were searched to collect cohort studies and case-control studies on the correlation between vitamin D deficiency in early pregnancy and preterm birth outcomes,and the retrieval time was from the establishment of the database to June 2019.Two researchers independently reviewed the literature,extracted the data and evaluated the risk of bias in the included studies.RevMan 5.3 software was used for Meta analysis.Result A total of 6 cohort studies and 3 nested case-control studies were included.A total of 30 891 newborns were included,including 1 912 premature infants.3 Chinese articles and 6 English articles were reviewed including three studies from China,three from North America,two from Europe and one from Australia.The diagnostic criteria for vitamin D deficiency and preterm birth were similar in these studies.After adjusting for age,race and other confounding factors,Meta-analysis results showed that vitamin D deficiency in early pregnancy did not increase the risk of preterm birth (OR =1.04,95％ CI 0.90 ～ 1.20,P =0.63).Subgroup analysis were conducted according to the study type,measurement method and regional population,and the results were consistent with the overall results.No significant publication bias was found in the meta-analysis results.Conclusion Current evidence suggests that vitamin D deficiency in early pregnancy has no significant influence on preterm birth.

近年来，免疫治疗在肿瘤治疗中取得了突破性的进展，为晚期肿瘤患者带来生存获益。在免疫治疗的应用中，部分患 者可以获得显著的疗效，仍有部分患者在疾病缓解的一段时间后出现疾病进展，提示存在免疫耐药。本文主要从原发性耐药及 获得性耐药两方面对肿瘤免疫治疗的耐药机制进行综述，同时分析了目前应用较为广泛的两种免疫治疗方法：免疫检查点抑制 剂及CAR-T细胞治疗，为克服耐药取得更好疗效提供参考。