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.

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.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Objective To investigate whether Dauricine(Dau)can ameliorate acute kidney injury induced by renal ischemia-reperfusion(IR)in mice.Methods C57BL/6 mice were randomly assigned to three experimental groups:sham operation,ischemia-reperfusion injury(IRI),and IRI treated with daunorubicin(IRI+Dau),with 12 animals in each group.Following oral administration of Dau(15 mg/kg),renal ischemia-reperfusion was induced,and blood and kidney tissue samples were collected 24 hours post-surgery.Histopathological changes were assessed using hematoxylin and eosin(HE)staining.Renal function was evaluated by measuring serum creatinine and blood urea nitrogen(BUN)levels.Protein expression related to lipid peroxidation was analyzed using western blotting and immunofluorescence.Inflammatory gene expression was determined via quantitative polymerase chain reaction(qPCR).Nuclear translocation of nuclear factor κB(NF-κB),a key inflammatory marker,was assessed using immu-nofluorescence.Statistical comparisons between groups were performed using t-tests.Results The administration of Dau significantly ameliorated IR-induced acute kidney injury compared to the Sham group.Serum creatinine(P<0.001)and urea nitrogen(P<0.000 1)levels were markedly decreased in Dau-treated mice relative to those in the IRI group.Furthermore,Dau significantly suppressed lipid peroxide production in renal tissues(P<0.001),without significantly affecting the expression levels of Gpx4(P=0.919)and Acsl4(P=0.086),two key proteins involved in lipid peroxidation.In addition,Dau effectively inhibited IR-induced nuclear translocation of NF-κB(P<0.001)and reduced apoptosis in kidney cells(P=0.004).Conclusion Dau mitigates IR-induced kidney damage by reducing the accumulation of lipid peroxides and inhibiting the nuclear translocation of NF-κB,thereby attenuating inflammation and renal cell apoptosis.

Tumor-associated neutrophils(TAN)are key components of the tumor microenvironment(TME)that exert dual regulatory roles in tumor progression through highly heterogeneous functional phenotypes.This review systematically addresses the dynamic balance of TAN in pro-tumor and anti-tumor mechanisms:TAN can directly kill tumor cells or collaborate with immune cells to activate anti-tumor re-sponses;however,in contrast,they can accelerate tumor progression by promoting angiogenesis,remodeling the extracellular matrix,and mediating immune evasion.Studies have shown that the functional heterogeneity of TAN is precisely regulated by multiple signaling net-works within the TME,and that the plasticity transformation of different subsets directly influences tumor progression.In-depth analyses of TAN subset characteristics,transformation mechanisms,and their clinical relevance will provide a theoretical basis for the development of inhibitors targeting pro-tumor neutrophils as well as advance the establishment of precise patient selection strategies for TAN subtype-based immunotherapy.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

Objective:To explore the role and mechanism of serum response factor (SRF) and lncRNA FGD5-AS1 in lung adenocarcinoma (LUAD).Methods:The plasma and tissue wax of LUAD patients treated in Tangshan People's Hospital from 2020 to 2022 and the plasma of healthy people were collected. The expression of SRF in LUAD tissues and cells, and the expression of lncRNA FGD5-AS1 in LUAD tissues, plasma and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of SRF and lncRNA FGD5-AS1 in LUAD tissue microarray were detected by immunohistochemistry and in situ hybridization. LUAD cells A549, H1299 and H1975 were cultured in vitro and divided into si-NC and si-SRF groups, si-NC and si-lncRNA FGD5-AS1 groups, pcDNA3.1 and lncRNA FGD5-AS1 groups, si-NC+pcDNA3.1/si-SRF+pcDNA3.1/si-SRF+lncRNA FGD5-AS1 groups. The effects of the above groups on the proliferation, invasion and migration of LUAD cells were detected by CCK-8, cloning formation, EdU, Transwell and scratch test. The JASPAR database was used to predict the downstream lncRNA FGD5-AS1 that can be regulated by SRF; double luciferase experiment, chromatin Immunoprecipitation (CHIP) and electrophoretic mobility shift assay (EMSA) experiment were used to verify the regulatory effect between SRF and lncRNA FGD5-AS1, and the subcutaneous tumorigenesis experiment in nude mice was used to detect the effects of cells that stably knock down SRF and stably overexpress lncRNA FGD5-AS1 on the growth of transplanted tumors. Results:The results of immunohistochemistry showed that the mean optical density of SRF in LUAD tissues (1.49±0.33) was higher than that in adjacent tissues (1.00±0.00, P＜0.001). The expression level of SRF in paraffin tissues of LUAD patients was higher than that in normal tissues adjacent to cancer ( P=0.037). CCK-8, cloning, scratch and Transwell experiments showed that knockdown SRF could inhibit the proliferation, migration and invasion of A549 and H1299 cells, respectively. [For A549 cells: The clone formation count, migration count, invasion count, and 48-h migration distance ratio were (233.70±18.50), (808.70±6.11), (489.70±53.00), and 1.00±0.03, respectively, in the si-NC group; and (131.30±22.50), (403.00±9.54), (372.70±26.27), and 2.14±0.09, respectively, in the si-SRF group. For H1299 cells: The clone formation count, migration count, invasion count, and 48-h migration distance ratio were (194.30±20.98), (988.70±64.52), (907.70±67.02), and 1.00±0.05, respectively, in the si-NC group; and (137.70±7.77), (665.70±157.10), (565.70±67.01), and 1.52±0.03, respectively, in the si-SRF group. All comparisons showed statistically significant differences ( P＜0.05)] JASPAR database prediction shows that SRF and lncRNA FGD5-AS1 have binding site. The double luciferase experiment, CHIP and EMSA experiments showed that SRF could regulate lncRNA FGD5-AS1. In situ hybridization showed that the mean optical density of lncRNA FGD5-AS1 in tissue microarray of LUAD patients (1.28±0.31) was higher than that in adjacent tissues (1.00±0.00, P＜0.001). The results of qRT-PCR experiment showed that the expression level of lncRNA FGD5-AS1 in wax tissues of LUAD patients was higher than that in normal tissues adjacent to cancer ( P=0.017). The expression level of lncRNA FGD5-AS1 in plasma of LUAD patients (3.48±2.62) was higher than that of healthy people (1.02±0.03, P＜0.001). CCK-8, cloning, EDU, scratch and Transwell experiments showed that overexpression of lncRNA FGD5-AS1 could promote cell proliferation [For A549 cells: The clone formation count, EdU-positive cell count, invasion count, and 48-h migration distance ratio were (22.67±5.86), (1.00±0.09), (135.70±13.20), and 0.35±0.02, respectively, in the pcDNA3.1 group; and (46.33±9.07), (1.65±0.10), (205.00±13.23), and 0.20±0.01, respectively, in the FGD5-AS1-overexpressing group. All comparisons showed statistically significant differences ( P＜0.05)], migration and invasion and vice versa [For H1975 cells: The clone formation count, EdU-positive cell count, invasion count, and 48-h migration distance ratio were (75.33±4.16), (1.00±0.02), (258.70±45.79), and 0.18±0.01, respectively, in the NC group; and (37.00±4.00), (0.52±0.07), (130.70±9.07), and 0.53±0.04, respectively, in the lncRNA FGD5-AS1 knockdown group (si-lncRNA FGD5-AS1 group). All comparisons showed statistically significant differences ( P＜0.05)]. Overexpression of lncRNA FGD5-AS1 could rescue the effect of knockdown SRF on the proliferation, migration and invasion of A549 and H1299 cells. The results of subcutaneous tumorigenesis experiment in nude mice indicated that the tumorigenicity of LUAD cells stably knockdown SRF was weakened and vice versa. Conclusion:SRF can promote the progress of LUAD by regulating lncRNA FGD5-AS1.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective:To evaluate the clinical efficacy of free anterolateral thigh perforator flap (ALTPF) for reconstruction of soft tissue defects in lower extremity in elderly patient.Methods:From February 2018 to August 2024, 24 elderly patients (14 males, 10 females. Age range: 70-89 years, mean age: 73.47 years) with soft tissue defects in lower extremity were treated with free ALTPFs in the Department of Hand Microsurgery, Sichuan Modern Hospital. All patients had comorbidities including chronic pulmonary diseases (10 cases), anaemia in various severity (15 cases), atherosclerosis (9 cases), diabetes mellitus (6 cases), hypertension (5 cases) and great saphenous varicose veins (4 cases). Fourteen patients were admitted to hospital though emergency department due to trauma. Of these patients, 2 underwent emergency flap transfer surgery, 12 had temporary wound coverage with negative pressure wound therapy (NPWT) or bone cement, followed by flap surgery at 3-7 days later. Ten patients with chronic wounds were admitted through outpatient clinic and underwent flap surgery at approximately 7 days after multidisciplinary team consultation and completion of preoperative preparation. A total of 15 patients received blood transfusion: 3 before the surgery, 10 in the surgery and 2 after the surgery. Defect locations were: right calf and ankle (6 cases), right foot (5 cases), left calf and ankle (10 cases) and left foot (3 cases). Defect sizes ranged from 5.0 cm×7.0 cm to 9.0 cm×30.0 cm, with exposure of tendon, bone or internal fixation. The size of ALTPFs ranged from 6.0 cm×8.0 cm to 10.0 cm×40.0 cm. All artery of flaps was end-to-end anastomosed with the recipient artery, and the vein of flaps was anastomosed with the accompanying vein by recipient artery. Donor sites were either closed directly or reconstructed with skin grafts. All patients were included in postoperative follow-up via visit of outpatient clinic or WeChat for evaluation of flap and donor sites.Results:All 24 flaps survived. Two cases presented with venous occlusion after surgery and surgical exploration discovered: 1 patient had a long-segment venous thrombosis in the recipient vein and was treated with great saphenous vein transposition for re-anastomosis; the other had a deep haematoma compressing of the flap, which was removed surgically with haemostasis. Follow-up lasted for 3 to 24 months. All donor sites healed well without local tenderness, leaving only linear or skin graft scars. The flap survived well, without infection, ulceration or necrosis. All ankle function was preserved.Conclusion:Transfer of free ALTPF is a valuable technique for treatment of soft tissue defects in lower extremity in elderly patients. Despite higher risks, satisfactory outcome can be achieved with thorough preoperative evaluation and surgical intervention, especially when the condition of a patient is stable, an early ambulation for functional recovery should be started.