The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective: To understand the current situation of school based sexuality education, attitudes and evaluations of teachers and students toward sexuality education, so as to provide evidence for promoting the development of school based sexuality education. Methods: From September to October 2021, 2 140 valid data from students in basic education and 2 146 from kindergarten and primary and secondary school teachers were collected by online questionnaire. The data were described and statistically analyzed, and the influencing factors of teachers willingness to teach sexuality education courses were explored by logistic regression analysis. Results: About 52.06% of the students had not received sexuality education in school, and 47.53% of the teachers did not carry out sexuality education in the school. Sexuality education in schools mainly focuses on reproductive health and physical development. About 48.93% of the teachers thought that the implementation of sexuality education in schools was not good, and the proportion of high school students who thought sexuality education in schools were "very bad" (32.87%) or "not very good" ( 21.23 %) was the highest. The teachers who undertook sexuality education were mainly mental health teachers (55.51% reported by teachers, 43.96% reported by students). About 71.02% of teachers believe that the best way to carry out sexuality education classes was to set up sexuality education curriculum. Students and teachers reported the need for sexuality education, and more than 50% of primary school students and high school students thought that sexuality education were "very needed" and "somewhat needed". About 51.77 % of teachers considered sexuality education "very urgent". All increased recognition of sexuality education, confidence in answering sex questions, external support for sexuality education, and acceptance of sexuality education training increased the likelihood of teachers teaching sexuality education ( OR =1.02, 1.95, 1.03, 3.53, P <0.05). Conclusion The current situation of school based sexuality education is not optimistic, the gap between sexuality education and students needs is wide, and the abilities of sexuality education teachers are insufficient.

Objective: To establish the Professional Standards for Sexuality Education Teachers in Kindergarten in China, so as to provide a basis for strengthening the construction of the sexuality education teacher team in kindergartens and promoting the smooth implementation of sexuality education in kindergartens. Methods: According to the Professional Standards for Kindergarten Teachers (Trial), combined with the existing research and practice results in the field of sexuality education at home and abroad and the development status of kindergarten sexuality education in China, the indicators and specific contents of Professional Standards for Sexuality Education Teachers in Kindergarten in China were selected. In September 2021, two rounds of Delphi expert consultation method were adopted to collect suggestions on professional standards from 34 experts in the field of sexuality education in China, and modifications were made according to the importance scores assessed by experts and specific suggestions until expert opinions converged. Then, the analytic hierarchy process (AHP) was used to assign weights to each indicator at each level, based on the relative importance between each two indicators at the same level as assessed by experts. Results: The Professional Standards for Sexuality Education Teachers in Kindergarten in China were initially established, including 3 primary indexes (professional concept, professional ability and professional knowledge), 7 secondary indexes and 27 tertiary indexes. The recovery rate of the two rounds of consultation documents was 100%, indicating that the experts were highly motivated. The authority coefficient of 2 rounds of expert consultation were both greater than 0.70, proving that the consultation results were reliable. The index weights of the three dimensions of professional concept, professional knowledge and professional ability were 0.44, 0.32 and 0.25, respectively. Conclusion The content of the Professional Standards for Sexuality Education Teachers in Kindergarten in China is complete, and the minimum qualified standard for kindergarten teachers engaged in sexuality education is determined.

Objective:To investigate the effect of folding and filling the orbicularis muscle flap of the inferiorcentral pedicle in correction of sunken upper eyelids.Methods:From August 2020 to April 2022, 39 female patients aged 36-63 (47.1±6.3) years with dermatochalasis and sunken upper eyelid were admitted to the Plastic Surgery Department of the First Affiliated Hospital of Air Force Medical University. During the surgery, the orbicularis oculi muscle in the skin resection area was preserved and a muscle flap was formed with the central part of the lower margin of the incision as the pedicle, which was folded deep and filled in the anterior orbital septal space. 6 months after surgery, the Park method was used to compare the effects before and after surgery, and the doctors and patients were scored on the Global Aesthetic Improvement Scale, respectively.Results:Unilateral upper eyelid hematoma appeared in 1 patient and healed after local acupuncture and aspiration, unilateral incision induration appeared in 2 patients, and gradually disappeared after 6 months of follow-up. The wounds of other patients healed in one stage. All the 39 patients were followed up for 6-12 months. The scores of the Global Aesthetic Improvement Scale at 6 months after surgery were (4.12±0.95) for doctors and (3.82±1.27) for patients. Park method showed that the degree of sunken upper eyelid after surgery was significantly better than that before surgery, and the difference was statistically significant ( Z=-7.721, P=0.000). Conclusions:The folding and filling of the orbicularis muscle flap of the eye with the inferior central pedicle can correct the laxity of the upper eyelid and improve the sunken upper eyelid. This operation can make full use of local tissue, and the effect is simple and lasting.

Non-neonatal tetanus is an acute, specific, toxic disease in patients over 28 days of age, characterized by continuous rigidity and paroxysmal spasms of the skeletal muscles throughout the body caused by the intrusion of Clostridium tetani through skin or mucosal membrane into the body and reproducing in anaerobic environments to produce exotoxins. The mortality rate of severe patients is close to 100% without medical intervention. Even with aggressive comprehensive treatment, the global mortality rate remains at 30%-50%, making it a potentially fatal disease. In order to standardize the diagnosis, treatment and prevention of non-neonatal tetanus, based on "Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2019 Edition)", experts have revised this regulation according to clinical practice and recent research progress in this field to guide medical institutions in the prevention and control of non-neonatal tetanus. This article interprets the key points and basis for updating the 2024 edition regulation to guide clinical implementation and application.

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

Objective:To investigate the clinical and pathological characteristics of adrenocortical carcinoma (ACC) patients, and to analyze the correlation between clinical features and Ki-67 index.Methods:Retrospectively analyze the clinical data of ACC patients admitted into Peking Union Medical College Hospital from January 1984 to January 2024. Inclusion criteria: ①The patient underwent puncture or surgery, and was diagnosed as ACC; or those who had typical manifestations of adrenocortical multi-band disorders, extremely high FDG uptake in the adrenal area and distant metastasis, and the diagnosis of ACC was considered after multidisciplinary consultation in our hospital; ②The patient had undergone thoracic, abdominal and pelvic CT scan, and could determine the size of the tumor and whether metastasis occurred. Exclusion criteria: ①without pathological diagnosis of ACC or no diagnosis of ACC without multidisciplinary consultation in our hospital; ②no records of symptoms, signs, examinations and other information at the time of initial diagnosis. The baseline data (age, gender, tumor side, etc.), clinical manifestations, endocrine examination, imaging and pathological examination results of the patients were collected, and the relationship between the maximum tumor diameter, the stage of the European Network for the Study of Adrenal Tumors (ENSAT), the functional status of the tumor, the maximum uptake value of 18F-FDG (SUVmax) and the Ki-67 index was analyzed. Results:A total of 164 patients were included in this study. There were 65 males and 99 females, with a male to female ratio of 1∶1.52. The median age at diagnosis was 48 (40, 58) years old. 71 tumors were located (43.29%) on the left side with 91 cases (55.49%) on the right side, and 2 cases (1.22%) on both sides. The median tumor diameter was 9 (7, 12) cm, of which 147 cases (147/158, 93.04%) were>5 cm. A total of 162 patients had ENSAT stages, including 9 stages Ⅰ(5.56%), 72 stage Ⅱ (44.44%), 51 stage Ⅲ (31.48%) and 30 stage Ⅳ(18.52%), respectively. Among the 154 cases with evaluable symptoms, 101 had no typical clinical manifestations and 53 patients had typical clinical manifestations. There were 41 cases (26.62%) of Cushing syndrome, 36 (23.38%) cases of abnormal sexual characteristics, and 19 cases (12.34%) of primary aldosteronism. 100 patients (64.94%) had abnormal endocrine examinations. The results of pathological examination showed 138 cases (90.20%) of traditional subtype, 13 cases (8.50%) of eosinophilic subtype, 1 case of mucinous type (0.65%) and 1 case of sarcomatoid ACC (0.65%). The detection rate of intravascular tumor thrombus was 14.63% (24/164), and the inferior vena cava and renal vein thrombus (10.37, 17/164) were the most common. The median Ki-67 index was 20% (10%, 40%), and 93.13% (122/131) had a Ki-67 index higher than 5%. The median Ki-67 index of ENSAT stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 20%(10%, 35%), 15%(10%, 30%), 30%(20%, 60%), 30%(20%, 60%), respectively. Compared with stage Ⅱ, ENSAT stage Ⅲ ( P=0.0007) and stage Ⅳ ( P=0.0011) ACC had a higher Ki-67 index; there was no statistical correlation between Ki-67 index and tumor maximum diameter, SUVmax of the primary lesion, and functional status of tumor (all P>0.05). Conclusions:ACC has the characteristics of late staging upon initial diagnosis, low proportion of patients with typical symptoms, and low detection rate of intravascular tumor thrombus. ENSAT stage was correlated with the Ki-67 index. Compared with Stage Ⅱ, ENSAT stage Ⅲ and Ⅳ ACC had a higher Ki-67 index.

Objective:To investigate the application of modified Hanley surgery in abscess of anal tube space (AATS), and its influences on anal function, interleukin (IL)-8 and IL-6.Methods:The clinical data of 96 patients with AATS from February 2020 to February 2022 in Shaoxing Central Hospital were retrospectively analyzed. Among them, 48 patients were treated with incision-thread drawing procedure (ITDP group), and 48 patients were treated with modified Hanley group (modified Hanley group). The curative effect, anal function, inflammatory factor level, neovascularization factor level and wound healing status were compared between the two groups.Results:There was no significant difference in the recovery rate between modified Hanley group and ITDP group: 100.00% (48/48) vs. 95.83% (46/48), χ2 = 0.51, P>0.05. The poor rate of anal function 2 months after surgery in modified Hanley group was significantly lower than that in ITDP group: 0 vs. 12.50% (6/48), and there was statistical difference ( P<0.05). The tumor necrosis factor-α(TNF-α), IL-8 and IL-6 24 h after surgery in modified Hanley group were significantly lower than those in ITDP group: (127.11 ± 13.96) ng/L vs. (160.59 ± 11.57) ng/L, (92.20 ± 11.62) ng/L vs. (124.33 ± 12.05) ng/L and (79.38 ± 12.47) ng/L vs. (100.07 ± 12.50) ng/L, and there were statistical differences ( P<0.01). The monocyte chemotactic protein-1 1 week after surgery in modified Hanley group was significantly lower than that in ITDP group: (92.85 ± 14.63) ng/L vs. (122.90 ± 15.59) ng/L, the vascular endothelial growth factor-A and transforming growth factor-β 1 were significantly higher than those in ITDP group: (188.06 ± 22.53) ng/L vs. (137.80 ± 19.52) ng/L and (1 897.6 ± 97.3) ng/L vs. (1 608.6 ± 98.1) ng/L, and there were statistical differences ( P<0.01). The pain score, edema score and neonatal granulation score 7, 14 and 21 d after surgery in modified Hanley were significantly lower than those in ITDP group, and there were statistical differences ( P<0.01). Conclusions:In the treatment of AATS, the modified Hanley surgery not only contributes to the thorough removal of the lesions, but also plays a positive role in protecting the anal function, reducing the level of inflammation, and promoting the recovery of endothelial function.