ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective To analyze the high risk factors of obstetric brachial plexus palsy(OBPP),and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification.Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center.The shortcomings of hospitals in birth weight assessment,delivery mode selection,labor process observation and shoulder dystocia management,and the causal relation-ship between them and the damage consequences of the children were summarized.Results Fault medi-cal behavior was assessed as the primary cause in 2 cases,equal cause in 10 cases,secondary cause in 8 cases,minor cause in 1 case,no causal relationship in 1 case,and unclear causal force in 3 cases.Conclusion In the process of forensic identification of OBPP,whether medical behaviors fulfill diagno-sis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation,de-livery mode notification,standardized use of oxytocin,standard operation of shoulder dystocia,etc.Meanwhile,it is necessary to fully consider the objective risk of different risk factors and the diffi-culty of injury prevention,and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

Objective To investigate the mechanism of the interaction between miR-9-5p and tissue metalloproteinase inhibitor 2(TIMP2)on autophagy and apoptosis in multiple myeloma(MM)cells.Methods Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect expression levels of miR-9-5p and TIMP2 in bone marrow samples of 9 patients with newly diagnosed MM and 9 patients with recurrent MM.The correlation of expression levels between the two were analyzed.U266 cells were divided into the miR-control group,the miR-9-5p group,the pcDNA3.1 group,the pcDNA3.1-TIMP2 group,the miR-9-5p+pcDNA3.1 group,and the miR-9-5p+pcDNA3.1-TIMP2 group.The effects of overexpressed miR-9-5p and TIMP2 on autophagy and apoptosis in U266 cells were detected by flow cytometry,immunofluorescence staining and Western blot experiments.The dual luciferase report experiment verified the interaction between miR-9-5p and TIMP2.Results Compared with newly diagnosed MM patients,the expression level of miR-9-5p was increased and the expression level of TIMP2 was decreased in patients with recurrent MM.The expression levels of miR-9-5p and TIMP2 were negatively correlated(P<0.05).Compared with the miR-control group,the miR-9-5p group showed a decrease in the expression level of MAP1LC3B-Ⅱ,an increase in expression levels of MAP1LC3B-Ⅰ and SQSTM1,and a decrease in cell apoptosis rate(P<0.05).Compared with the pcDNA3.1 group,the expression level of MAP1LC3B-Ⅱ was increased in the pcDNA3.1-TIMP2 group,while the expression levels of MAP1LC3B-Ⅰ and SQSTM1 were decreased,and the apoptosis rate of cells increased(P<0.05).Bioinformatics and dual luciferase reporter experiments confirmed that TIMP2 was the target gene of miR-9-5p.Conclusion miR-9-5p inhibits autophagy and apoptosis in MM cells by targeting TIMP2,thereby promoting the occurrence and development of MM.

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ²=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ²=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ²=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.
Pregnancy ; Child ; Animals ; Dogs ; Female ; Humans ; Male ; Allergens ; Cross-Sectional Studies ; Retrospective Studies ; Respiratory System ; Asthma

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ²=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ²=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ²=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.
Pregnancy ; Child ; Animals ; Dogs ; Female ; Humans ; Male ; Allergens ; Cross-Sectional Studies ; Retrospective Studies ; Respiratory System ; Asthma

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Objective:To evaluate the efficacy and safety of non-submucosal injection in endoscopic submucosal excavation (ESE) for small submucosal tumors originating in the muscularis propria of the stomach.Methods:A total of 138 patients diagnosed as having small gastric muscularis propria tumors (≤2 cm) at Digestive Endoscopy Center of Zhejiang Provincial Hospital of Chinese Medical from November 2018 to October 2020 were randomly divided into the observation group with non-submucosal injection of ESE and the control group with submucosal injection of ESE for a randomized controlled trial. The exposure time, tumor removal time, operation cost, hospitalization period, numbers of metal clips and complications of the two groups were analyzed and compared.Results:A total of 138 patients were enrolled, including 76 patients in the observation group and 62 patients in the control group. All lesions were successfully and completely removed. Compared with the control group, the observation group had shorter median tumor exposure time [2.00 min VS 3.30 min, Z=-2.426, P =0.045], shorter median tumor removal time [16.8 min VS 34.4 min, Z=-4.324, P<0.001], less median surgical cost [2 903 yuan VS 3 178 yuan, Z=-5.112, P<0.001], and fewer metal clips used (4.0±0.6 VS 5.1±1.3, t=1.452, P=0.003). The incidence of postoperative abdominal distension of the observation group was lower [9.2% (7/76) VS 22.6% (14/62), χ2=2.512, P=0.049], the incidence of postoperative abdominal pain of this group was lower too [11.8% (9/76) VS 32.3% (20/62), χ2=4.242, P=0.014], but there was no significant difference in the period of hospitalization, incidence of postoperative fever or perforation ( P>0.05). Conclusion:Non-submucosal injection of ESE is safe and effective for submucosal tumors smaller than 2.0 cm originating from the muscularis propria of the stomach , which might be more advantageous than traditional ESE.