SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

In compliance with the data requirements for monitoring medical service capacity and quality safety in the sec-ond part of the"Rules for the Implementation of Evaluation Standards for Tertiary General Hospitals in Hubei Province(2023 Edition)",this paper,in conjunction with the specific circumstances of a tertiary hospital,carried out a brief overview of the da-ta collection process and the challenges faced during the reevaluation of the tertiary hospital.By accurately addressing the prob-lems and challenges in medical services,this paper aimed to enhance medical quality management and advance the hospital's high-quality development.

Cellular senescence and fibrosis are two biological processes that are closely related to the development of many diseases.Cellular senescence can occur through mechanisms such as telomere shortening,DNA damage,and oxidative stress,leading to degradation of cell function and decreased ability to repair damage.More and more studies have shown that fibrosis and cell senescence are closely related,and cell senescence has been confirmed to be involved in the occurrence and development of scar fibrosis diseases.An in-depth understand-ing of the relationship between cellular senescence and scar fibrosis is helpful to find new therapeutic strategies and develop targeted drugs to reduce the process of scar fibrosis.

Pyroptosis is a newly discovered kind of cell death modality that, due to its association with innate immunity, plays a crucial role in cytolysis and inflammatory cytokine release during host defense against infection. In recent years, studies have shown that pyroptosis plays an important role in the occurrence and development of liver diseases. This article introduces and elaborates on the most recent research progress on pyroptosis in liver diseases based on the morphological features, molecular and pathophysiological mechanisms.

Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

OBJECTIVE: To investigate effectiveness of a novel suture method-stepwise progressive ultra-tension-reducing suture method in closing high-tension wounds on the chest, back, and limbs. METHODS: A retrospective analysis was conducted on 25 patients with high-tension wounds on the chest, back, and limbs who were treated with stepwise progressive ultra-tension-reducing suture method between January 2022 and December 2022. Among the patients, there were 8 males and 17 females, with an average age of 30.5 years (range, 18-56 years). All wounds after scar or tumor resection were located on the chest, back, upper limbs, and lower limbs in 8, 6, 9, and 2 cases, respectively. The size of wounds ranged from 3.5 cm×2.8 cm to 40.0 cm×15.0 cm. All patients were advised to use topical silicone-based treatments postoperatively. The protrusion of the incision, the height of the protrusion, and the duration of the tension reduction effect were observed. The scar formation at the incision site at 6 months after operation was observed, the scar appearance was evaluated by Vancouver Scar Scale (VSS) score, and the scar width was measured. The patient's satisfaction and adverse reactions to incisions were also evaluated. RESULTS: The incisions significantly elevated, with a height of 0.3-2.5 cm, and the tension reducing effect lasted for 8.5-18.0 weeks after operation, with an average of 13.6 weeks. All incisons healed by first intention. One patient experienced transient hyperpigmentation, which resolved spontaneously. Three keloid patients showed localized redness postoperatively, and 2 experienced local recurrence, which improved significantly after treatment with triamcinolone, 5-fluorouracil injections, and laser therapy. All patients were followed up 6.0-13.5 months, with an average of 10.1 months. At 6 months after operation, all patients had linear scars, with VSS scores ranging from 1.0 to 3.5 (mean, 2.0). The width of the scars ranged from 0.5 to 3.0 mm (mean, 1.4 mm). The patients expressed satisfaction with the effectiveness. CONCLUSION The stepwise progressive ultra-tension-reducing suture method for high-tension wounds can effectively reduce the tension at the wound edges, providing a prolonged tension-reducing effect and satisfactory effectiveness.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Suture Techniques ; Adolescent ; Young Adult ; Cicatrix/prevention & control* ; Wound Healing ; Back ; Treatment Outcome ; Sutures ; Thorax ; Extremities/surgery*

Objective:To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA).Methods:The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged ( M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results:The elderly (age≥60 years) ( OR=2.428, 95% CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) ( OR=1.089, 95% CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) ( OR=1.122, 95% CI: 1.078 to 1.168), total bilirubin (every rise of 1 μmol/L) ( OR=2.629, 95% CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95% CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion:The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.

At present, effective reconstruction of the integrity and functionality of damaged skin tissue remains an important medical problem in the field of wound repair. In recent years, the rapid development of nanozymes and tissue engineering scaffolds in the field of regenerative medicine has made it possible to develop new skin wound repair materials. Based on the process of skin wound repair and regeneration, this review briefly describes the nanozymes and its catalytic mechanism. At the same time, the common tissue engineering scaffolds loaded with nanozymes and their manufacturing strategies are introduced, the application of tissue engineering scaffolds loaded with nanozymes during the stages of anti-bacteria and anti-inflammation in the process of wound repair is summarized, and their future development direction is discussed.