Building on the theory of "state-target differentiation and treatment" proposed by Academician TONG Xiaolin， diabetic foot ulcers （DFUs） are considered to belong to the "collateral injury" stage， characterized by the interplay of five states，i.e. dampness， heat， stasis， deficiency， and impairment. The dynamic biological process of epithelial-mesenchymal transition （EMT） is closely associated with the healing process of DFUs. The treatment of DFUs through staged differentiation under the "state-target differentiation and treatment" theory not only provides a basis for precise clinical treatment， but also offers insights into the regulatory roles of EMT in different states and potential intervention targets. The dampness state typically exits during the inflammatory phase， local inflammation and fluid metabolism disorders inducing EMT. Treatment focuses on draining dampness and alleviating edema， promoting local microcirculation， and improving tissue hypoxia. The heat state often reflects acute local inflammatory responses. Treatment emphasizes clearing heat and resolving toxins， regulating the EMT process to reduce inflammation， control infection， and alleviate redness， swollen， heat， and pain in the affected area. The stasis state mainly occurs during the proliferation phase. Treatment centers on invigorating blood and dissolving stasis， and unblocking the channels and quickening the collaterals. EMT plays a role in remodeling the extracellular matrix， promoting tissue repair and angiogenesis. The deficiency state is common in chronic phase， where treatment prioritizes tonifying qi and nourishing blood while reinforcing healthy qi and dispelling pathogens. EMT regulation focuses on restoring local tissue metabolism and improving the micro-environment to enhance tissue repair capacity. The impairment state represents the progression of disease deterioration. Treatment should focus on supplementing qi， blood， yin， and yang， and also promoting muscle growth and strengthening bones， supplementing by resolving toxins and stasis. EMT plays a role by regulating the activity of extracellular matrix-degrading enzymes to prevent excessive tissue repair and scarring， thereby facilitating the reconstruction of normal tissue structures.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

ObjectiveTo observe the effect of tendon clearing combined with Zizhu ointment on the serum levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasomes， interleukin （IL）-1β， and IL-18 in the treatment of non-ischemic diabetic foot ulcers. MethodA total of 106 patients with non-defective diabetic foot ulcers who attended the outpatient clinic and wards of the Vascular Surgery Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2023 to March 2024 were selected. The patients with non-ischemic diabetic foot ulcers who met the inclusion criteria were assigned with the random number table method into an observation group and a control group， with 53 patients in each group. Patients in both groups received basic treatment. The local ulcers in the observation group received tendon clearing combined with Zizhu ointment， while those in the control group received conventional debridement combined with topical solution of bovine basic fibroblast growth factor. The serum NLRP3， IL-1β， and IL-18 levels， ulcer area， traditional Chinese medicine （TCM） symptom scores， visual analogue scale （VAS） score， and DMIST score were measured and recorded in the two groups before and after treatment. The ulcer healing rate and incidence of adverse reactions were compared between the two groups. ResultThe observation group had higher ulcer healing rate than the control group （P<0.01）. After treatment， both groups showed lowered serum NLRP3， IL-1β， and IL-18 levels， reduced ulcer area， and declined TCM symptom score， VAS score， and DMIST score （P<0.01）. Moreover， these indicators were lower in the observation group than in the control group （P<0.05， P<0.01）. Neither group showed significant changes in the liver and kidney function indicators after treatment. Significant adverse reactions occurred in neither group during the treatment course. ConclusionTendon clearance combined with Zizhu ointment was effective and safe in treating non-ischemic diabetic foot ulcers. It may exert the therapeutic effect by reducing the inflammation of the local ulcers.

Objective:To analyze the epidemic trend of tuberculosis (TB) in adolescents in China from 2000 to 2019.Methods:We used data from Global Burden of Disease Study 2019 to describe the epidemic trend of TB. The estimated annual percentage changes (EAPC) of the morbidity and mortality were calculated to assess epidemic trends from 2000 to 2019.Results:In 2019, a total of 37 815.670 TB cases and 213.629 deaths were reported in adolescents in China, the morbidity was 25.938/100 000 and the mortality was 0.147/100 000. The cases and deaths of TB in 2019 decreased by 71.84% and 89.90% respectively compared with 2000. In 2019, the incident case number (21 371.747) was 1.30 times higher in male adolescents than in female adolescents (16 443.923), and was 4.11 times higher in age group 15-19 years (30 420.054) than in age group 10-14 years (7 395.616). From 2000 to 2019, the morbidity (EAPC=-3.95, 95% CI: -4.34- -3.55) and mortality (EAPC=-9.18, 95% CI: -9.33- -9.02) of TB in the adolescents showed decreasing trends. The morbidity and mortality of drug-sensitive TB, extensively drug-resistant TB and multidrug-resistant TB all showed decreasing trends. Conclusions:The morbidity and mortality of TB and its subtypes among adolescents in China decreased during 2000-2019. More attention should be paid to male adolescents and adolescents aged 15-19 years due to relatively higher incidence intensity of TB.

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

Objective:To evaluate the safety and effectiveness of the model repair strategy for preputial defect in hypospadias surgery.Methods:From February 2017 to December 2022, 59 children in our hospital with an average age of (6.9±3.2) years were retrospectively analyzed. All of them were children with multiple failed hypospadias operations. According to the condition of penile scrotum skin, different methods of penile skin reconstruction were selected. Among them, 20 patients underwent penile skin flap reconstruction with simple foreskin and multiple small incision reduction, 22 patients with penile and scrotal transposition underwent penile lateral scrotum flap to complete ventral penis coverage, and 12 patients underwent middle scrotum flap with pedicled flap to cover ventral urethra. The penis was covered by inferior epigastric artery perforator flap in 5 patients.Results:The wound healed completely one week after the operation and no obvious scar formation was observed. The ventral flap of the penis was covered by the lateral scrotal flap of the penis, and no flap necrosis and wound infection were observed. The ventral urethra was covered with pedicled skin flap in the middle scrotal suture. The flap survived without scrotal hematoma. The inferior epigastric artery perforator flap was used to cover the patients with penile defect, all the flaps survived, and no complications such as wound infection and abdominal hernia occurred. No urethral fistula or urethral diverticulum was reported in all the patients. Urethral stricture occurred in 1 case of scrotal suture pedicled flap group and 1 case of lateral penis scrotal flap group, which was cured after expansion. One case with small incision and one case with lateral scrotal skin were cured after secondary repair by Mathieu method.Conclusions:For children with a history of multiple hypospadias operations, coverage of ventral skin defects of the penis is essential to reduce complications and obtain good appearance. This study summarized four effective strategies for covering penile defect from simple to complex. The small incision was used to reduce the expansion of all flaps. The lateral penile scrotal flap is more suitable for patients with penile scrotal transposition. The pedicled flap of scrotal suture and inferior superficial artery perforator flap are suitable for the repair of larger defect area.