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.

Objective:This article explores the diagnosis and treatment of a special type of laryngeal foreign body with granuloma in children, providing a clinical reference for standardized diagnosis and treatment. Methods:This article retrospectively analyzes one case admitted to our department and five other cases reported in relevant literature involving a special type of laryngeal foreign body with granuloma in children. It summarizes the clinical characteristics of this disease and explores its diagnosis and treatment. Results:①A total of 6 cases were misdiagnosed and had a long course of illness. Five cases had no clear history of foreign body at the first visit. One case had foreign body history but no foreign body was found. ②The clinical symptoms were diverse, which could be hoarseness, cough, wheezing, dyspnea, or no symptoms. ③A total of 3 cases were diagnosed by laryngoscopy, and 3 cases were diagnosed by laryngoscopy and imaging examination. ④Foreign bodies that were not wrapped in granulomas, were removed first and then the granulomas were treated; foreign bodies wrapped in granulomas were removed after the removal of granulomas. Conclusion:A special type of laryngeal foreign body with granuloma may lack of accurate foreign body history, resulting in long-term retention of foreign bodies, leading to granuloma formation and misdiagnosis. Electronic laryngoscopy combined with CT examination contribute to early diagnosis. Low temperature plasma under endoscope and anesthetic laryngoscope is conducive to the exposure and precise removal of foreign bodies and avoids tracheotomy to a certain extent.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Foreign Bodies/surgery* ; Granuloma, Foreign-Body/therapy* ; Larynx/pathology* ; Retrospective Studies

Objective:To explore the efficacy of using drug combination and sublingual immunotherapy（SLIT） for pediatric obstructive sleep apnea（OSA） and allergic rhinitis（AR） after adenotonsillectomy, in order to provide a more optimized treatment plan after the surgery. Methods:A total of 95 pediatric OSA combined with AR were selected. According to the treatment plan, they were divided into the SLIT group（postoperative medication combined with SLIT） and the control group（postoperative medication treatment only）. The comparisons were made between the two groups regarding the scores of the 18-item Quality of Life Questionnaire for Obstructive Sleep Apnea（OSA-18） and the Visual Analogue Scale（VAS） before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment; the monthly total medication scores（TMS） from 1 month to 3 months, 4 months to 6 months, 7 months to 1 year, and 1 year to 2 years after treatment, as well as the number of acute attacks of AR in the 1st year and 2nd year after treatment; and the Lund-Kennedy scores and nasal resistance grading of nasal endoscopy before and at 1 month, 3 months, 6 months, 1 year, and 2 years after treatment. The effectiveness and safety were also analyzed. Results:After one year of treatment, the OSA-18 score, VAS score, TMS and Lund-Kennedy score in the SLIT group were significantly better than those in the control group. The nasal resistance was significantly reduced（P<0.05）, and the frequency of AR attacks was significantly lower than that in the control group（P<0.05）. After 2 years of treatment, the VAS score, Lund-Kennedy score and nasal resistance classification in the SLIT group tended to stabilize, while the OSA-18 score continued to decline. Conclusion:After surgery for pediatric OSA combined with AR, the use of drugs combined with SLIT can effectively alleviate AR symptoms, further improve OSA-related symptoms and quality of life, reduce drug dependence, decrease the frequency of AR attacks, and enhance the long-term efficacy of the surgery.
Humans ; Sleep Apnea, Obstructive/surgery* ; Rhinitis, Allergic/therapy* ; Quality of Life ; Child ; Tonsillectomy ; Treatment Outcome ; Adenoidectomy ; Sublingual Immunotherapy ; Drug Therapy, Combination ; Male ; Female

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

Objective:To investigate the efficacy of high-flux hemodialysis in the treatment of stage 5 chronic kidney disease and its effects on nutritional status.Methods:A retrospective study was conducted on 64 patients with stage 5 chronic kidney disease who received treatment at Hangzhou Third People's Hospital from February 2023 to February 2024. These patients were divided into an observation group and a control group according to different blood purification methods, with 32 patients per group. The control group underwent conventional hemodialysis treatment, while the observation group underwent high-flux hemodialysis. Renal function, calcium and phosphorus metabolism, inflammatory factors, and nutritional indicators were compared between the two groups before and after treatment.Results:After treatment, the observation group showed significantly lower levels of serum creatinine [(238.18 ± 64.37) μmol/L] and blood urea nitrogen [(8.35 ± 1.43) μmol/L] compared with the control group [(343.12 ± 75.28) μmol/L, (10.97 ± 1.64) μmol/L, t = 5.99, 6.81, both P < 0.05]. The observation group had lower levels of calcium [(1.65 ± 0.19) mmol/L] and phosphorus [(1.54 ± 0.28) mmol/L] compared with the control group [(2.16 ± 0.23) mmol/L, (2.03 ± 0.36) mmol/L, t = 9.67, 6.08, both P < 0.05]. After treatment, the levels of C-reactive protein in the observation group [(9.72 ± 2.65) mg/L] were lower than those in the control group [(14.98 ± 3.76) mg/L, t = 6.47, P < 0.001]. However, there were no significant differences in hemoglobin, albumin, and prealbumin levels between the two groups ( t = -0.47, -0.16, -0.48, all P > 0.05). Conclusions:High-flux hemodialysis is effective in patients with stage 5 chronic kidney disease. It significantly alleviates the inflammatory state, but it has no notable effects on nutritional status. This approach merits consideration in clinical practice.

Objective:To explore perioperative management strategies for hiatal hernia in patients 70 years old or above.Methods:The perioperative clinical data of 102 patients (≥70 years) undergoing minimally invasive hiatal hernia repair from January 2019 to December 2024 was retrospectively analyzed.Results:The elderly group age ranged from 70 to 95 years,including 32 males and 70 females with disease duration of 0.67-51 years (mean 10.1 years), showing 68.63% comorbidity incidence (70 cases). Postoperative complication rates were 22.55%, with no severe complications occurring within one month after surgery.Conclusions:Hiatal hernia patients 70 years old or above exhibit longer disease histories, higher comorbidity rates, and increased postoperative complications. Comprehensive preoperative assessment, precise minimally invasive intraoperative techniques, and enhanced perioperative management ensure safe anesthesia and surgical implementation, improve surgical safety, and facilitate patient recovery.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.