ObjectiveTo observe the clinical efficacy of Shentong Zhuyutang combined with Dilongtang in the treatment of lumbar disc herniation （LDH） with Qi stagnation and blood stasis syndrome， and its effect on nucleus pulposus reabsorption and immune-inflammatory factors， exploring its therapeutic mechanism from the perspective of reabsorption. MethodsA total of 120 patients with LDH from the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine， treated between June 2020 and January 2023， were randomly divided into the control group （52 cases， with 8 dropouts） and the observation group （49 cases， with 11 dropouts） according to a random number table. The control group received routine treatment， while the observation group was treated with Shentong Zhuyutang combined with Dilongtang in addition to routine treatment. Visual Analogue Scale （VAS）， Oswestry Disability Index （ODI）， Japanese Orthopaedic Association （JOA） score， and traditional Chinese medicine （TCM） syndrome score were measured before treatment and after 3 courses of treatment. Venous blood samples were collected for the determination of serological indexes. MR examination was performed during the 6-month follow-up to calculate the absorption rate. ResultsAfter treatment， both groups showed significant reductions in VAS， ODI， TCM syndrome score， serum tumor necrosis factor （TNF）-α， matrix metalloproteinase （MMP）-9， and vascular endothelial growth factor （VEGF） levels， and a significant increase in JOA score compared with pre-treatment values （P<0.05）. Compared with the control group， the observation group showed significantly lower VAS， ODI， TCM syndrome score， serum TNF-α， MMP-9， and VEGF levels， and a significantly higher JOA score （P<0.05）. The proportion of nucleus pulposus reabsorption in the observation group was 57.14% （28/49）， significantly higher than 21.15% （11/52） in the control group （χ²=6.161， P<0.05）. ConclusionShentong Zhuyutang combined with Dilongtang can effectively relieve pain， improve lumbar function， and alleviate TCM clinical symptoms in LDH patients with Qi stagnation and blood stasis syndrome. Imaging findings suggest that the treatment promotes the reabsorption of nucleus pulposus protrusion， while laboratory testing shows reduced serum levels of TNF-α， MMP-9， and VEGF， which contribute to the rehabilitation of patients.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

BACKGROUND:More and more animal experiments and clinical studies have confirmed that electrical stimulation can promote the repair of peripheral nerve injury,but the specific mechanism is not yet fully understood. OBJECTIVE:To investigate the effect of electrical stimulation-induced miR-741-3p regulating Radil on Schwann cell migration. METHODS:(1)Twelve male SD rats were randomly divided into electrical stimulation group and control group.The electrical stimulation group received continuous electrical stimulation for 7 days after sciatic nerve compression injury,while the control group was not treated after sciatic nerve compression.The injured nerves were taken on day 7 after operation.The expression difference of miR-741-3p between the two groups was verified by fluorescence in situ hybridization.(2)The target genes of miR-741-3p were predicted by miRDB,TargetScan,and miRWalk databases.(3)Schwann cells were transfected with miR-741-3p mimetic and its control,miR-741-3p inhibitor and its control,Radil siRNA and its control,miR-741-3p inhibitor+Radil siRNA and miR-741-3p inhibitor+siRNA control.The transfection efficiency was detected by RT-PCR.The migration ability of Schwann cells was detected by Transwell chamber. RESULTS AND CONCLUSION:(1)The fluorescence intensity of miR-741-3p in the electrical stimulation group was lower than that in the control group.(2)The results of database prediction showed that 69 genes might be the target genes of miR-741-3p.Radil was one of the predicted target genes,which was mainly involved in cell adhesion and migration.(3)Compared with the miR-741-3p inhibitor control group,the number of Schwann cell migration increased in the miR-741-3p inhibitor group(P<0.05).Compared with the miR-741-3p mimic control group,the number of Schwann cell migration in the miR-741-3p mimic group decreased(P<0.05).Compared with the siRNA control group,the number of Schwann cell migration was decreased in the Radil siRNA group(P<0.05).(4)Compared with miR-741-3p inhibitor control group,the expression level of Radil was increased in miR-741-3p inhibitor group.Compared with miR-741-3p mimic control group,the expression level of Radil was decreased in miR-741-3p mimic group.(5)Compared with miR-741-3p inhibitor+siRNA control group,the number of Schwann cell migration was reduced in miR-741-3p inhibitor+Radil siRNA group(P<0.05).The results showed that electrical stimulation promoted the migration of Schwann cells by down-regulating miR-741-3p and targeting Radil gene.

Objective To systematically evaluate toxicities of nifedipine in pregnant women with hypertension, and provide references for nifedipine’s clinical safety application. Methods Study was conducted with data from US food and drug administration adverse event reporting system（FARES） database from January 1, 2015, to March 31, 2021. Information component （IC） and reporting odds ratio（ROR）methods were applied for signal mining. Results Finally, a total of 539278 records of pregnant women with hypertension were selected for analysis, and 70 positive adverse drug event signals were detected. Premature delivery （IC₀₂₅=2.87，ROR₀₂₅=9.52）, pre-eclampsia （IC₀₂₅=1.82，ROR₀₂₅=3.82） and fetal growth restriction （IC₀₂₅=2.37，ROR₀₂₅=5.69）were positive adverse events with higher frequency. Polydactyly（IC₀₂₅=3.13， ROR₀₂₅=10.05）, fetal death（IC₀₂₅=2.93，ROR₀₂₅=8.57）and premature delivery（IC₀₂₅=2.87，ROR₀₂₅=9.52）were positive adverse events with higher intensity. Vascular resistance systemic increased, small for dates baby and fetal death corresponded to higher death rates. Conclusion Nifedipine-associated drug toxicities were detected in pregnant women with hypertension, and some adverse events with high frequency and high death rate were deserved further attention by medical staffs.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

In recent years, with the clinical application of minimally invasive surgical techniques and comprehensive preoperative treatment, the survival rate of locally advanced esophageal cancer has significantly improved. However, the treatment of metastatic esophagogastric cancer still relies mainly on systemic therapy, and immunotherapy combined with chemotherapy has become a first-line treatment option, prolonging the survival of patients with metastatic esophageal cancer. Oligometastatic esophageal cancer is expected to bring survival benefits through systemic therapy combined with local treatment. The 2024 European clinical practice guidelines for oligometastatic esophagogastric cancer have been officially released, which standardize the definition, diagnosis, and treatment of oligometastatic esophageal cancer for further prospective studies. The authors interpret this guideline, especially by reviewing the clinical evidence of oligometastatic esophageal squamous cell carcinoma, to provide reference for the diagnosis and treatment of oligometastatic esophageal cancer in China.

ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

ObjectiveTo investigate the bacterial diversity in the rhizosphere soil and phyllosphere of Angelica sinensis and examine the effects of foliar applications of a composite bacterial agent，salicylic acid，and coronatine on the bacterial diversity，disease incidence，and plant yield，thus providing a theoretical basis and guidance for the artificial construction of functional minimal communities and the regulation of rhizosphere through foliar treatments. MethodsUnder continuous cropping conditions in the field，foliar applications of a composite bacterial agent，salicylic acid，coronatine，and sterile water were conducted. The 100-plant weight was measured via the conventional method，and the incidence of diseases was recorded. The microbial community composition，diversity，and inter-group differences in the phyllosphere and rhizosphere soil of A. sinensis were analyzed by 16S high-throughput sequencing，and the potential microbial functions were predicted. ResultsCompared with the blank control，foliar applications of salicylic acid and coronatine both significantly reduced the yield and root rot incidence of A. sinensis. The foliar application of salicylic acid decreased the content of ferulic acid and increased that of ligustilide. The foliar application of coronatine increased the content of both ferulic acid and ligustilide. The microbial communities and functions in the phyllosphere and rhizosphere soil were significantly different. The phyllosphere had lower microbial diversity，with all bacteria being Gram-negative，mainly Cyanobacteria and Proteobacteria with limited functions. The rhizosphere soil had higher microbial diversity，harboring dominant phyla including Proteobacteria，Actinobacteria，Acidobacteria，and Bacteroidetes with rich functions. All foliar treatments regulated the microbial community in the rhizosphere soil，with a more significant effect on the microbial community in the rhizosphere soil than that in the phyllosphere. The coronatine treatment significantly reduced the abundance of Proteobacteria and nitrate-reducing and aromatic compound-degrading microorganisms in the rhizosphere soil，thus affecting nutrient cycling and autotoxic substance degradation and leading to a yield reduction. Compared with the salicylic acid treatment，the coronatine treatment significantly increased the abundance of Bacillus and Streptomyces in the rhizosphere soil，demonstrating enhanced disease control efficacy. ConclusionFoliar application of coronatine and salicylic acid can significantly regulate the composition and function of bacterial communities in the rhizosphere soil，thereby reducing the disease incidence and the plant yield.

ObjectiveTo dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. MethodsTwenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. ResultsCompared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. ConclusionThe vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.