3CL protease (3CLpro) of SARS-CoV-2 is a pivotal enzyme required in coronavirus replication and transcription. Its highly conserved structure and the absence of homologous proteins in the host make it an ideal target for broad-spectrum anti-coronavirus drug development. In this work, we systematically investigated and compared the binding modes and dynamic properties of the four stereoisomers of a pyridyl-urea diyne ester (PyDU) molecule with two chiral centers within the 3CLpro active site. Through molecular docking, MD simulations, MM/GBSA binding free-energy calculations, and DCCM analysis, all four stereoisomers were stabilized primarily by hydrophobic packing. Among them, the (R,S) isomer exhibited the best overall performance, including docking score, binding free-energy components, and key residue interactions. The (R,S) and (S,R) isomers also enhanced the cooperative motions around the binding pocket, while the (R,S) isomer further modulated the flexibility of domain III, which may influence 3CLpro dimerization. Conversely, the (S,S) isomer exhibited the weakest affinity due to insufficient hydrophobic contact. By innovatively integrating chirality, binding energy and protein dynamical features, we revealed the dual role of chirality in modulating affinity and dynamic responses, which provides a theoretical basis for the chiral-guided design of coronavirus inhibitors.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

OBJECTIVE T o analyze the distribution and clinical characteristics of carbapenem-resistant organisms(CRO)in the intestinal and respiratory tracts of high-risk ICU patients,and to evaluate the effectiveness of two screening methods:plate screening and Gene Xpert Carba(hereinafter referred to as Xpert Carba).METHODS In-testinal samples(anal swabs,feces)and respiratory samples(sputum,lavage fluid)from 320 patients admitted to the ICU ward of the Fourth Affiliated Hospital of Soochow University from Apr.2023 to Dec.2024 were collected.Plate screening and Xpert Carba methods were used for active screening of CRO strains,and clinical data of patients were collected through electronic medical records.RESULTS The plate screening results indicated that 70 out of 573 samples from 320 patients tested positive for CRO,with a positive rate of 12.22％(70/573).The positive rates for anal swabs,feces,sputum and lavage fluid were 9.26％(20/216),10.39％(8/77),13.02％(22/169)and 18.02％(20/111),respectively.There was no statistically significant difference in the positive rates among different sample types.The predominant CRO-positive organisms detected were Klebsiella pneumoniae in intestinal samples and Pseudomonas aeruginosa in respiratory samples.Among 361 intestinal and respiratory samples tested from 88 patients,plate screening and Xpert Carba screening showed the positive rates of 14.40％(52/361)and 6.37％(23/361),respectively.Analysis of the clinical characteristics of the 31 CRO-posi-tive patients revealed that they were predominantly elderly(average age 69 years),with 51.61％(16/31)having a history of interdepartmental transfers and 48.39％(15/31)having surgerical history.The mechanical ventilation usage rate in the respiratory positive group(58.82％,10/17)was higher than that in the intestinal positive group(0,0/7)and the dual positive group(14.28％,1/7).Compared with Xpert Carba,plate screening had lower screening costs,higher positive rates across different sample types and a broader range of detected bacterial species.CONCLUSIONS The ICU ward is a high-prevalence area for CRO strains,with K.pneumoniae(from in-testinal samples)and P.aeruginosa(from respiratory samples)showing the highest isolation rates.Plate screen-ing boasts lower costs,higher detection rate and broader bacterial species coverage for active screening of CRO strains in the intestinal and respiratory tracts of high-risk ICU patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients' clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens. METHODS: This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients. RESULTS: With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS ( P = 0.012) and EFS ( P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs . 6 [4, 7] days, Z = -0.227, P = 0.820). CONCLUSIONS NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Female ; Lung Neoplasms/mortality* ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy/methods* ; Retrospective Studies ; Aged ; Adult ; Kaplan-Meier Estimate ; Treatment Outcome ; Immunotherapy/methods*

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.