OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

Ethical review represents the core of the scientific and technological ethical governance， and its quality depends on the participation of ethics. The absence of ethics and ethical experts will compromise the quality of the review. According to the spirit of the Guidelines on Strengthening the Governance over Ethics in Science and Technology， this paper analyzed the process of separating scientific and technological ethics from the field of scientific research morality， clarified the ethical attributes of ethical review， and argued that scientific research and technological innovation activities originated from ethics. On this basis， the fundamental principle of “ethics first” was proposed， aiming to proactively embed ethical considerations throughout the entire process of scientific and technological activities. This principle was the primary requirement for ensuring governance effectiveness and can also eliminate the risk of ethics being obscured in ethical governance. In practice， “ethics first” manifested specifically in dimensions such as prioritizing academic systems， prioritizing publicity， education， and training， as well as further advancing ethical considerations.

Drug clinical trials constitute a critical link in new drug development and an essential means to verify the safety and efficacy of pharmaceuticals. The protection of participants’ rights and interests and the prevention of risks directly affect the scientific ethics and social credibility of the trials. Vulnerable groups， due to restricted autonomous decision-making capacities or special social status， are more susceptible to safety risks. Children are a typical representative of vulnerable groups. Their physiological particularities， cognitive limitations， and dependence collectively epitomize the universal protection demands of vulnerable research participants. Taking children as an instance， this paper analyzes the current weak links in the protection of pediatric research participants. Integrating advanced international experience with domestic practical demands， it comprehensively identified protection risk points at every stage and constructed a multi-stakeholder collaborative mechanism for the full-process protection of pediatric research participants. This mechanism incorporated seven main entities， including drug regulatory authorities， sponsors， researchers， and ethics committees， covering the pre-trial， intra-trial， and post-trial phases to meet the requirements of full-chain and multi-dimensional protection. It provided references for the subsequent establishment of a systematic protection mechanism for vulnerable populations.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Objective:To evaluate the safety and efficacy of digital technology-assisted debridement and bone and soft tissue reconstruction in the treatment of chronic osteomyelitis of the tibia.Methods:This retrospective study analyzed clinical data from 38 patients (26 males, 12 females; mean age 45.61±18.36 years, range 16-83 years) with chronic post-traumatic osteomyelitis complicated by soft tissue defects in the tibia, treated at the Department of Orthopaedics, Fourth Medical Center of PLA General Hospital between June 2021 and June 2023. There were 18 cases of traffic accidents, 6 cases of high-altitude falls, 6 cases of heavy objects and 6 cases of low-energy falls. Lesion sites: 12 cases in the upper segment of the tibia, 12 cases in the middle segment, and 14 cases in the lower segment. According to the Cierny-Mader classification, there were 24 cases of type III and 14 cases of type IV. Before the operation, the "3D point cloud technology" was used to plan the debridement range of bone and soft tissue. During the operation, the optical navigation system was used to monitor the debridement range in real time. The flap was designed by combining "Reading Tablet Treasure" with CT angiography, and the amount of bone graft was predicted by AI algorithm. The surgical method adopted is the Masquelet technique, namely thorough debridement, bone cement occupation and soft tissue repair in the first stage, and bone reconstruction in the second stage. Comparing the calculated bone defect amount and soft tissue defect area before the operation with the actual measured values after debridement. The cure rate of infection was evaluated by using the McKee bone infection treatment criteria after the operation. The visual analogue scale (VAS) for pain, lower extremity functional scale (LEFS), and self-rating anxiety scale (SAS) were used to evaluate the improvement of the quality of life of postoperative patients.Results:38 patients were followed up with a mean follow-up of 13.53±2.37 months. 37 patients' infections were effectively controlled, and 1 patient had a recurrence of infection, with an effectiveness rate of 97% for the treatment of McKee's infections. The preoperative calculated bone defect amount and soft tissue defect area were 51.05±26.31 cm 3 and 68.42±43.45 cm 2 respectively, and the actual measured values after debridement during the operation were 51.66±26.35 cm 3 and 68.82±43.76 cm 2 respectively. There was no statistically significant difference before and after the operation ( P>0.05). The interval between the first and second stage surgeries was 10.36±1.61 weeks, and all flaps survived after the first stage surgery. Two months after the operation, one case had recurrent osteomyelitis. After palliative treatment, sinus tracts were formed at the infection site. At the 12-month regular dressing change follow-up, there were still purulent secretions in the sinus tracts. There was no recurrence of infection after primary debridement in 37 cases, and the bone grafts healed. The bone healing time was 3.58±0.97 months. The postoperative VAS, LEFS, and SAS scores were 1.00±0.91, 66.68±7.91, and 34.30±4.29, respectively, which were significantly improved compared with the preoperative scores of 7.54±1.52, 21.22±4.29, and 52.70±6.74, respectively, and the difference was statistically significant ( P<0.05). Conclusions:The application of digital technology to precisely design the debridement range of bone and soft tissue, and the real-time holographic visualization monitoring of the debridement range during the operation can achieve precise debridement of bone and soft tissue and personalized and precise repair of soft tissue defects. It is a safe and effective technique for the treatment of chronic osteomyelitis of the tibia.

Objective:To evaluate the efficacy and safety of the Masquelet technique on the basis of characterization of hematogenous and traumatic chronic osteomyelitis of the tibia.Methods:A retrospective analysis was conducted with chronic tibial osteomyelitis who had been treated by the Masquelet technique at Department of Orthopedic Surgery, The Fourth Medical Center, PLA General Hospital from February 2021 to June 2023. The patients were classified into 2 groups based on the underlying etiology of their conditions: a hematogenous group and a traumatic group. Treatment efficacy was evaluated in terms of infection control rate, bone graft healing time, visual analog scale (VAS) pain score, anxiety measured by the self-rating anxiety scale (SAS), and lower limb function assessed by the lower extremity functional scale (LEFS).Results:A total of 66 patients with chronic tibial osteomyelitis were included in the study. There were 17 cases in the hematogenous group. They were 11 males and 6 females with a median age of 31.0 (15.0, 45.0) years and a median disease duration of 3.0 (1.5, 8.0) months. The median interval between the first and second-stage surgeries was 11.5 (8.0, 13.0) weeks, the median volume of bone defect 25.0 (15.0, 40.0) cm 3, and the median bone graft healing time 4.0 (3.0, 4.0) months. No bacteria were detected in secretion culture in 6 cases and Staphylococcus aureus was found in 6 cases. At 12 months postoperatively, the median VAS score was 1.0 (0.0, 2.0) point, the median SAS score 27.0 (20.0, 32.0) points, and the median LEFS score 78.0 (75.0, 80.0) points. There were 49 cases in the traumatic group. They were 36 males and 13 females with a median age of 52.0 (42.0, 63.0) years and a median disease duration of 6.0 (3.0, 36.0) months. The median interval between the first and second-stage surgeries was 10.0 (8.0, 17.0) weeks, the median volume of bone defect 30.0 (22.0, 53.0) cm 3, and the median bone graft healing time 3.5 (3.0, 4.5) months. No bacteria were detected in secretion culture in 10 cases and Staphylococcus aureus was found in 19 cases. At 12 months postoperatively, the median VAS score was 2.0 (1.0, 3.0) points, the median SAS score 35.0 (28.0, 42.0) points, and the median LEFS score 54.0 (42.0, 60.0) points. According to the McKee criteria for infection treatment, 14 cases achieved complete recovery, 2 ones showed improvement, and 1 case experienced recurrence in the hematogenous group, while 44 cases achieved complete recovery, 4 ones showed improvement, and 1 case experienced recurrence in the traumatic group. Conclusions:Although hematogenous and traumatic cases of chronic osteomyelitis of the tibia differ in terms of age of onset, disease duration, and lesion extent, Staphylococcus aureus is the predominant pathogen in both conditions. Application of the Masquelet technique has proven to be an effective treatment for both conditions with comparable bone graft healing time.

During the past decate, Chinese pathologists have made remarkable achievements in the area of soft tissue tumors. They have not only done in-depth researches in selected entities like liposarcoma and round cell sarcomas, but have also issued expert consenses and guideline, as well as published professional books and translation books, with purpose to comprehensively improve the level of diagnosis nationwide.

Objective:To establish a prediction model for larger for gestational age(LGA)infants in pregnant women with gestational diabetes mellitus(GDM)in order to improve pregnancy outcomes.Methods:A retro-spective analysis was performed on the clinical data of 338 pregnant women with GDM who underwent routine prenatal examinations and were hospitalized for delivery in the First Affiliated Hospital of Nanjing Medical Universi-ty from January 1,2018 to December 31,2023.Pregnant women with complete HbAlc data during pregnancy were divided into a training set of 241 cases and a validation set of 97 cases.Lasso and Logistic regression analysis and variable screening combined with previous clinical experience were used to construct a nomogram model,and its degree of differentiation and calibration were evaluated.Result:①By Lasso regression analysis,age,family histo-ry of type 2 diabetes,body mass index(BMI),gestational weight gain(GWG),fasting blood glucose(FBG),postprandial 1-hour blood glucose(1h PBG),HbAlc,free triiodothyronine(FT3),free thyroxine(FT4)and insulin treatment were important predictors of LGA.②Multivariate Logistic regression analysis showed that GWG and HbAlc were independent risk factors for LGA in pregnant women with GDM(OR＞1,P＜0.05).③Combined with Lasso and Logistic regression analysis,previous literature reports and clinical experience,BMI,GWG,FBG,1h PBG,HbAlc and FT3 were selected as independent variables,and LGA as dependent variable.A nomogram pre-diction model was constructed in the training set,and the C-index of 0.71.ROC curve analysis showed that the AUC values of the training set and the validation set were 0.709 and 0.700,respectively,and the discriminative a-bility of the model was acceptable.The calibration curve of the model was close to the ideal curve,and the clinical decision curve suggested that the model showed a positive net benefit at the threshold of 10％to 50％.Conclu-sion:The predictive model has certain value in predicting the occurrence of LGA in pregnant women with GDM,and provides help for early diagnosis,treatment and clinical intervention of GDM and its complications,in order to improve perinatal and long-term adverse outcomes.

Endometriosis is a common estrogen-dependent disease in women of childbearing age,often leading to chronic pelvic pain,infertility,ovarian cancer,and other serious complications,and jeopardizing the health of women.The pathogenesis of endometriosis is complex and involves the alteration of multiple signaling pathways mediated by hormones,immunity,genetics,and the environment,and their interactions.Wnt/β-catenin signaling is involved in the regulation of embryonic development and tissue homeostasis,and it has recently been implicated in the pathogenesis of endometriosis via multiple pathways.This review considers the biological characteristics of the Wnt/β-catenin signaling pathway and summarizes the main mechanisms and signaling pathways involved in the pathogenesis of endometriosis,as well as the curr-ent research status of the regulation of this signaling pathway by traditional Chinese medicine for the treatment of endometriosis.We aim to clarify how the Wnt/β-catenin signaling pathway affects the development of endometriosis,and suggest that future studies should focus on exploring its potential role as an indicator for the clinical prediction and early diagnosis of endometriosis,thus providing theoretical support for the early diagnosis of this condition and the development of targeted drugs.