Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

The ability to localize sound sources rapidly allows human beings to efficiently understand the surrounding environment. Previous studies have suggested that there is an auditory "where" pathway in the cortex for processing sound locations. The neural activation in regions along this pathway encodes sound locations by opponent hemifield coding, in which each unilateral region is activated by sounds coming from the contralateral hemifield. However, it is still unclear how these regions interact with each other to form a unified representation of the auditory space. In the present study, we investigated whether functional connectivity in the auditory "where" pathway encoded sound locations during passive listening. Participants underwent functional magnetic resonance imaging while passively listening to sounds from five distinct horizontal locations (-90°, -45°, 0°, 45°, 90°). We were able to decode sound locations from the functional connectivity patterns of the "where" pathway. Furthermore, we found that such neural representation of sound locations was primarily based on the coding of sound lateralization angles to the frontal midline. In addition, whole-brain analysis indicated that functional connectivity between occipital regions and the primary auditory cortex also encoded sound locations by lateralization angles. Overall, our results reveal a lateralization-angle-based representation of sound locations encoded by functional connectivity patterns, which could add on the activation-based opponent hemifield coding to provide a more precise representation of the auditory space.
Humans ; Sound Localization/physiology* ; Male ; Female ; Magnetic Resonance Imaging ; Young Adult ; Functional Laterality/physiology* ; Adult ; Brain Mapping ; Auditory Cortex/physiology* ; Acoustic Stimulation ; Auditory Pathways/physiology* ; Brain/physiology*

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

ObjectiveTo investigate the clinical efficacy of Gandouling tablet （GDL） on abnormal lipid metabolism in Wilson's disease （WD） and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD. MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， serum triglyceride （TG）， total cholesterol （TC）， apolipoprotein B （ApoB）， low density lipoprotein cholesterol （LDL-C）， bile acid （BA）， γ-glutamyl transferase （GGT）， prediction model of hepatic steatosis ［hepatic steatosis index （HSI） and Zhejiang University index （ZJU index）］， ultrasonic attenuation coefficient imaging （ATT）， and traditional Chinese medicine （TCM） syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG， TC， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome score， ATT， and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method， with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate （DMPS）， while the control group was only treated with DMPS as a control. After six courses of treatment， 24-hour urine copper， TC， TG， LDL-C， ApoB， HSI， ZJU， ATT， TCM syndrome score， and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC， TG， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome scores， and ATT was analyzed. ResultPearson correlation analysis showed that serum TC （r = 0.811）， TG （r = 0.826）， LDL-C （r = 0.802）， ApoB （r = 0.820）， ALT （r = 0.497）， ALT/AST （r = 0.826）， TCM syndrome score （r = 0.716）， and ATT （r = 0.736） were positively correlated with HSI （P<0.01）， while AST， BA， and GGT had no significant correlation with HSI. TC （r = 0.718）， TG （r = 0.765）， LDL-C （r = 0.667）， ApoB （r = 0.699）， ALT/AST （r = 0.403）， TCM syndrome score （r = 0.666）， and ATT （r = 0.684） were positively correlated with ZJU （P<0.01）. ALT， AST， BA， and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 （37/43）， and that of the control group was 72.09% （31/43）. The total effective rate of the observation group was higher than that of the control group （Z = -2.301， P<0.05）. After treatment， the 24-hour urine copper of the two groups increased significantly. The levels of TC， TG， LDL-C， and ApoB were significantly decreased， and the HSI， ZJU， and ATT were significantly decreased （P<0.01）. Compared with those in the control group after treatment， the above indexes improved better in the observation group （P<0.05， P<0.01）. ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD， with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.

Objective:To assess the efficacy of modified arthroscopic lower trapezius transfer with autologous hamstring tendon bridging for irreparable massive posterosuperior rotator cuff tears.Methods:A retrospective analysis was conducted on 59 patients (11 males and 48 females; mean age 66.70±6.10 years, range 55-79 years) treated between June 2019 and November 2022 for posterior superior irreparable massive rotator cuff tears. The treatment involved total arthroscopic oblique muscle transposition combined with partial rotator cuff repair. Shoulder mobility was measured in active supination, forward flexion, posterior external rotation, and abduction external rotation before surgery and at the final follow-up. The Constant-Murley shoulder function score, visual analogue scale (VAS) for pain, and American Shoulder and Elbow Surgeons (ASES) scores were assessed preoperatively, at 3 months, 6 months postoperatively, and at the final follow-up. MR examinations were conducted preoperatively and at 3, 6, and 12 months postoperatively to evaluate rotator cuff healing and retear rates.Results:All surgeries were successfully completed using an average of 3.2±0.5 anchor nails (range 3-5) per case. The mean follow-up period was 15.9±5.7 months (range 12-37 months). Significant improvements in shoulder mobility were observed postoperatively compared to preoperative measurements. The mean body external rotation angle increased from 12.0°±19.4° preoperatively to 35.3°±19.6° at the final follow-up ( P<0.05), and the mean abduction external rotation angle increased from 33.4°±22.4° to 43.4°±23.1° ( P<0.05). The mean preoperative abduction angle improved from 121.7°±47.9° to 136.4°±40.6° ( P<0.05), and the mean forward flexion supination angle improved from 117.6°±45.8° to 139.5°±33.7° ( P<0.05). Postoperative VAS scores significantly improved from 4.8±1.8 preoperatively to 0.3±0.8 at the final follow-up ( F=104.868, P<0.001). The ASES scores improved from 42.0±14.9 preoperatively to 71.7±14.6 at the final follow-up ( F=47.287, P<0.001). The Constant-Murley scores increased from 54.3±17.1 preoperatively to 76.4±13.0 at the final follow-up ( F=44.082, P<0.001). Postoperative complications included 2 complete tears and 7 partial tears (re-tear rate 15.3%). No serious complications such as shoulder joint infection, joint stiffness, or vascular nerve injury were observed. One patient developed a localized subcutaneous hematoma at the tendon extraction site, and another developed deep vein thrombosis of the lower extremity, which improved with symptomatic anticoagulation. Conclusion:Modified arthroscopic lower trapezius transfer with autologous hamstring tendon bridging effectively reduces shoulder pain, improves shoulder joint activity and function scores, and is associated with a low rate of surgical complications for patients with irreparable massive posterosuperior rotator cuff tears.

Objective:To investigate the clinical efficacy of thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point on lumbodorsal myofascial pain syndrome of cold-damp stagnation type.Methods:A total of 90 patients with lumbodorsal myofascial pain syndrome of cold-damp stagnation type admitted to Zhejiang Provincial Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to April 2022 were included in this study. They were randomly divided into three groups ( n = 30/group) using the random number table method. Patients in the Chinese herbal ointment group were treated by external application of Chinese herbal ointment at the trigger point. Patients in the thunder-fire moxibustion group were treated with thunder-fire moxibustion. Patients in the combined therapy group were treated with thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point. All patients were treated for 28 consecutive days. Clinical efficacy was compared among the three groups. Before and after treatment, the Visual Analogue Scale score, local tenderness score, Oswestry Disability Index score and Pittsburgh Sleep Quality Index score were compared among the three groups. Results:Total response rate (96.67%) in the combined therapy group was significantly higher than 73.33% in the thunder-fire moxibustion group and 66.67% in the Chinese herbal ointment group ( χ2 = 9.01, 4.70, both P < 0.05). Visual Analogue Scale score and local tenderness score in the combined therapy group were (1.96 ± 0.93) points and (1.00 ± 0.69) points, respectively, which were significantly lower than (2.43 ± 0.87) points and (1.37 ± 0.56) points in the thunder-fire moxibustion group and (2.77 ± 0.86) points and (1.50 ± 0.57) points in the Chinese herbal ointment group ( F = 6.22, 5.38, both P < 0.05). The Oswestry Disability Index score in the combined therapy group was (19.80 ± 3.80) points, which was significantly lower than (22.30 ± 2.82) points in the thunder-fire moxibustion group and (23.60 ± 3.71) points in the Chinese herbal ointment group ( F = 9.07, both P < 0.05). After treatment, the Pittsburgh Sleep Quality Index score in the combined therapy group was (5.30 ± 1.12) points, which was significantly lower than (6.50 ± 1.33) points in the thunder-fire moxibustion group and (6.73 ± 1.41) points in the Chinese herbal ointment group ( F = 10.59, both P < 0.05). Conclusion:Thunder-fire moxibustion combined with external application of Chinese herbal ointment at the trigger point is highly effective on lumbodorsal myofascial pain syndrome of cold-damp stagnation type than monotherapy. The combined therapy can markedly reduce pain and greatly improve lumbodorsal function and sleep quality.

Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.

Objective:To explore the value of competency-oriented training mode in the training of professional postgraduate students of thoracic surgery.Methods:A total of 71 professional postgraduate students, who entered thoracic surgery department for rotation training, were divided into experimental group and control group. Among them, 33 students in experimental group accepted competency-oriented training, including medical theoretical knowledge, clinical skills, clinical thinking, scientific information and interpersonal communication, while 38 students in control group received traditional training. Before leaving the department, the two groups of students had a unified assessment, and their results were compared and analyzed. SPSS 19.0 was used to make statistical analysis on the students' assessment results, and the comparison of the two groups of students' results was made by two independent samples t test. Results:The experimental group performed better in theoretical knowledge, clinical skills, clinical thinking and total scores than control group [(14.21±2.03) points vs. (12.97±2.06) points, (24.30±2.35) points vs. (22.37±3.10) points, (24.00±1.85) points vs. (22.71±3.17) points, (78.09±3.53) points vs. (73.34±5.25) points], with significant differences (all P<0.05). Conclusion:Competency-oriented training model can significantly enhance the training quality of professional postgraduates of thoracic surgery. We should make rational use of new media means and various teaching platforms, and give full play to the characteristics and advantages of the discipline, which facilitates to improving the clinical post competence of trainees.