Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveTo comprehensively identify the O-methyltransferase （OMT） genes in Carthamus tinctorius and explore the key OMTs that can catalyze the methylation of flavonoids， providing a basis for understanding the molecular formation mechanism of the structural diversity of flavonoids in C. tinctorius. MethodsThe hidden Markov model was used to systematically identify the type Ⅰ OMTs from the high-quality genome data of C. tinctorius. A suite of bioinformatics tools was employed to systematically analyze the physicochemical properties， gene structure， conserved motifs， chromosomal localization， gene replication events， and collinearity of the identified genes. The target gene was heterologously expressed through the prokaryotic expression system of E. coli， and the protein function was verified by in vitro enzymatic reactions. ResultsA total of 31 type Ⅰ OMTs were identified. CtFOMT1 was successfully cloned and expressed in a soluble form in Escherichia coli. The recombinant protein was purified via Ni²⁺ affinity chromatography to obtain a high-concentration preparation. In vitro enzymatic assays demonstrated that CtFOMT1 utilized S-adenosylmethionine as the methyl donor to catalyze the methylation of the 4′-OH of naringenin， resulting in the production of isosakuranetin. A similar process occurred with the 4′-OH of luteolin， leading to the formation of diosmetin. Subsequent methylation of the 3′-OH group of diosmetin generated 4′-methylchrysoeriol. ConclusionCtFOMT1 can catalyze the methylation of 4′-/3′-OH in the flavonoid skeleton. It is hypothesized that CtFOMT1 may play a role in the biosynthesis of various 4′-/3′-oxymethyl flavonoids in C. tinctorius.

The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

OBJECTIVE To observe the clinical efficacy of mycophenolate mofetil （MMF） combined with Budesonide enteric capsules in the treatment of high-risk progressive immunoglobulin A nephropathy （IgAN）. METHODS A total of 150 adult patients with high-risk progressive IgAN who attended the Department of Nephrology， Chongqing University Three Gorges Hospital， between August 1， 2024 and March 1， 2025 were enrolled in this study. The control group （ n ＝94） received MMF combined with glucocorticoid， while the observation group （ n ＝56） received MMF combined with Budesonide enteric capsules. The 24-hour urine protein （24 h UP）， estimated glomerular filtration rate （eGFR）， and albumin （ALB） levels of patients in both groups were compared at 1， 2， 3， and 6 months post-treatment. The complete response （CR） rate and overall response rate were calculated for both groups at 1， 2， 3， and 6 months post-treatment. Adverse reactions occurring during treatment were compared between the two groups. RESULTS Compared with before treatment， 24 h UP decreased significantly in both groups at different time points after treatment （ P ＜0.05）， and ALB increased significantly （ P ＜0.05）. However， there was no significant change in eGFR （ P ＞0.05）. The 24 h UP in the observation group at 1， 2， and 3 months after treatment was significantly lower than that of the control group （ P ＜0.05）， while the ALB level was significan tly higher （ P ＜0.05）. However， at 6 months after treatment， there was no statistically significant difference in these two indicators between the two groups （ P ＞0.05）. There was no statistically significant difference in eGFR between the two groups at different time points after treatment （ P ＞0.05）. The overall response rates in the observation group at 1 and 2 months after treatment were significantly higher than those in the control group （ P ＜0.05）. There was no statistically significant difference in the overall response rate at the remaining treatment time points and the CR rate at all time points between the two groups （ P ＞0.05）. Patients in the observation group had significantly lower rates of skin abnormalities， elevated blood glucose， and overall adverse reactions compared with the control group （ P ＜0.05）. CONCLUSIONS Compared with MMF combined with glucocorticoids， MMF combined with Budesonide enteric capsules for the treatment of high-risk progressive IgAN patients can reduce proteinuria and improve serum ALB levels more quickly， significantly increase the early overall response rate， and significantly reduce glucocorticoid-related skin adverse reactions， blood glucose elevation， and the overall incidence of adverse reactions， demonstrating a better short-term benefits.

Diabetic nephropathy（DN） is a common and severe microvascular complication of diabetes. In recent years， the classical herbal formula Shenqi dihuang decoction has demonstrated unique advantages in the clinical treatment of DN. This article conducts a systematic review of the mechanisms of action and clinical applications of Shenqi dihuang decoction in the treatment of DN. It reveals that the mechanism by which this formula improves DN involves multi-target synergistic regulation. For instance, Shenqi dihuang decoction exerts multiple pharmacological effects by regulating signaling pathways including phosphatidy linostiol 3-kinase/protein kinase B， AMP-activated protein kinase/silent information regulator 1/forkhead box O1， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathways.These effects include regulating glucose and lipid metabolism， inhibiting oxidative stress， reducing inflammation， improving insulin resistance， modulating cell death （apoptosis/autophagy/ferroptosis/pyroptosis）， and preventing renal fibrosis. Existing clinical studies indicate that Shenqi dihuang decoction and its modified formulas， alone or in combination with other therapeutic methods， can significantly improve glucose and lipid metabolism， reduce proteinuria， and delay renal function decline in patients with DN. These effects are superior to those of Western medicines such as irbesartan， valsartan， and empagliflozin， and the treatment demonstrates good safety. Future research should leverage systems biology and artificial intelligence technologies to further elucidate the integrated mechanisms in the treatment of DN by Shenqi dihuang decoction， thereby advancing the precision and standardization of its clinical application.

ObjectiveTo explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective To systematically evaluate the efficacy and safety of robot-assisted laparoscopic surgery (RAS) and conventional laparoscopic surgery (CLS) in hiatal hernia repair. Methods PubMed, Cochrane Library, CNKI, Web of Science, VIP, and Wanfang databases were searched to collect literature comparing the efficacy and safety of RAS and CLS for hiatal hernia repair published from their inception to November 7, 2023. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies, and RevMan 5.4.1 software was used for meta-analysis. Results A total of 15 retrospective cohort studies with 18239 patients were finally included. The NOS scores of the included literature were all ≥7 points. Meta-analysis results showed that RAS was superior to CLS in terms of postoperative complications as the primary outcome [OR=0.56, 95%CI (0.42, 0.77), P<0.01]. There was no statistical difference between the two methods in terms of average operation time [MD=−0.74, 95%CI (−12.99, 11.51), P=0.91], average intraoperative blood loss [MD=−24.47, 95%CI (−54.80, 5.87), P=0.11], intraoperative complications [OR=0.76, 95%CI (0.29, 2.01), P=0.58], average postoperative hospital stay [MD=−0.24, 95%CI (−0.75, 0.27), P=0.36], postoperative GERD score [MD=−0.04, 95%CI (−0.41, 0.33), P=0.81], and 30-day readmission rate [OR=0.60, 95%CI (0.30, 1.20), P=0.15]. The cost of CLS surgery was less than that of RAS [SMD=1.59, 95%CI (1.16, 2.01), P<0.01]. Conclusion RAS has comparable efficacy and safety to CLS in hiatus hernia repair.

Esophageal cancer is a common malignancy with high incidence and poor prognosis. Conventional therapies fail to provide long-term benefits for patients, with postoperative recurrence and metastasis being the primary reasons for treatment failure. With the continuous development of nanomedicine, nanoparticle-based drug delivery has received widespread attention as a novel therapeutic approach. Among them, Fe3O4 magnetic nanoparticles have achieved a series of encouraging advancements in the treatment of esophageal cancer, owing to their unique superparamagnetism and biocompatibility. This paper provides a review of the relevant research on Fe3O4 magnetic nanoparticle-based drug delivery systems for the treatment of esophageal cancer.