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:To analyze the perioperative risks and prognosis in patients with differentiated thyroid cancer (DTC) complicated by Graves' disease (GD) .Methods:Clinical data of 880 DTC patients who underwent radical thyroidectomy at the Department of General Surgery, the First Medical Center of Chinese PLA General Hospital between Jan. 2016 and Dec. 2022 was retrospectively collected. The cohort included 119 DTC patients with GD (hyperthyroid group) and 761 DTC patients with normal thyroid function without GD (normal group) . Use propensity score matching (PSM) was used to obtain cohorts with balanced baseline characteristics between the hyperthyroid and normal groups. Perioperative risks and prognos were compared between the two groups.Results:For perioperative risk comparison, after 1∶2 matching, 116 patients were included in the hyperthyroid group and 232 patients in the normal group. The operation time was longer in the hyperthyroid group compared to normal group ([107.26±30.27]min vs. [96.45±32.51]min, P=0.003) . There were no statistical differences between the two groups in intraoperative blood loss, postoperative drainage volume or postoperative hospital stay ( P>0.05) . There were no statistical difference in the incidence of complications such as temporary or permanent hypoparathyroidism, temporary or permanent recurrent laryngeal nerve injury, and lymphatic leakage between the two groups. For prognostic comparison, after 1∶2 matching, 117 cases were included in the hyperthyroid group and 234 cases in the normal group. During follow-up period, 16 patients experienced DTC recurrence, including 5 cases in the hyperthyroid group and 11 cases in the normal group. There was no statistical difference in reccurence-free survival rates between the two groups (5-year RFS: 95.7% vs. 95.3%, P=0.907) . Multivariate Cox regression analysis revealed GD was not the risk factor for DTC recurrence. Conclusions:With standardized and adequate preoperative preparation, the perioperative risks of DTC patients complicated by GD were not increased compared to patients without GD. Additionally, GD does not increase the risk of postoperative tumor recurrence in DTC patients.

Objective Investigate the clinical efficacy and application value of gasless trans-subclavian approach endoscopic surgery(GTAES)for the treatment of primary hyperparathyroidism(PHPT).Methods 55 PHPT patients who underwent unilateral parathyroid adenoma resection from January 2023 to October 2024 were absorbed.Based on surgical approaches,31 patients were divided into the traditional low-collar arc incision open surgery group(open group)and 24 patients were divided into gasless trans-subclavian approach endoscopic surgery group(endoscopic group).The perioperative data,anterior neck function recovery,and incision healing were compared between two groups.Results There were no significant differences in operation time,intraoperative blood loss,postoperative drainage volume and postoperative hospital stay between the two groups(P＞0.05).The preoperative blood calcium levels of the endoscopic group and the open group were(2.68±0.10)mmol/L and(2.63±0.16)mmol/L,respectively.The blood calcium levels on the first day after surgery were(2.39±0.12)mmol/L and(2.36±0.16)mmol/L,respectively.Preoperative parathyroid hormone(PTH)was 27.55(110.05,155.75)pg/ml in endoscopic group and 137.00(107.00,210.30)pg/ml in open group,respectively.PTH on the first day after surgery was 18.98(12.64,23.53)pg/ml and 13.85(7.36,23.23)pg/ml,respectively.Blood calcium and PTH in each group 1 day after surgery decreased compared with that before surgery,and the difference was statistically significant(P＜0.05).There were no postoperative complications such as hoarseness,bleeding and incision infection in both groups.Postoperative hand and foot numbness:5 cases(20.8％)in endoscopic group and 8 patients(25.8％)in the open group,there was no significant difference between the two groups(P=0.667).There was no significant difference in the score of neck pain 3 days after surgery between the two groups(P＞0.05).The score of swallowing tension[(1.92±1.06)points compared with(2.77±1.38)points,P=0.015]and the score of anterior neck discomfort[(1.63±0.88)points compared with(2.35±1.33)points,P=0.018]in the endoscopic group one month after surgery were better than those in the open group.There was no significant difference in the score of neck scar scale between the two groups 3 months after surgery(P＞0.05).VAS score of incision satisfaction was(9.08±0.88)in endoscopic group and(8.19±1.30)in open group,and the endoscopic group was better than the open group,the difference was statistically significant(P=0.004).Conclusion For PHPT patients caused by unilateral parathyroid adenoma confirmed through preoperative localization examination,GTAES is a safe and effective surgical approach,which offers unique advantages in intraoperative lesion identification,cosmetic outcomes of the incision,and preservation of anterior neck function,providing a new surgical option for PHPT patients.

Objective Investigate the clinical efficacy and application value of gasless trans-subclavian approach endoscopic surgery(GTAES)for the treatment of primary hyperparathyroidism(PHPT).Methods 55 PHPT patients who underwent unilateral parathyroid adenoma resection from January 2023 to October 2024 were absorbed.Based on surgical approaches,31 patients were divided into the traditional low-collar arc incision open surgery group(open group)and 24 patients were divided into gasless trans-subclavian approach endoscopic surgery group(endoscopic group).The perioperative data,anterior neck function recovery,and incision healing were compared between two groups.Results There were no significant differences in operation time,intraoperative blood loss,postoperative drainage volume and postoperative hospital stay between the two groups(P＞0.05).The preoperative blood calcium levels of the endoscopic group and the open group were(2.68±0.10)mmol/L and(2.63±0.16)mmol/L,respectively.The blood calcium levels on the first day after surgery were(2.39±0.12)mmol/L and(2.36±0.16)mmol/L,respectively.Preoperative parathyroid hormone(PTH)was 27.55(110.05,155.75)pg/ml in endoscopic group and 137.00(107.00,210.30)pg/ml in open group,respectively.PTH on the first day after surgery was 18.98(12.64,23.53)pg/ml and 13.85(7.36,23.23)pg/ml,respectively.Blood calcium and PTH in each group 1 day after surgery decreased compared with that before surgery,and the difference was statistically significant(P＜0.05).There were no postoperative complications such as hoarseness,bleeding and incision infection in both groups.Postoperative hand and foot numbness:5 cases(20.8％)in endoscopic group and 8 patients(25.8％)in the open group,there was no significant difference between the two groups(P=0.667).There was no significant difference in the score of neck pain 3 days after surgery between the two groups(P＞0.05).The score of swallowing tension[(1.92±1.06)points compared with(2.77±1.38)points,P=0.015]and the score of anterior neck discomfort[(1.63±0.88)points compared with(2.35±1.33)points,P=0.018]in the endoscopic group one month after surgery were better than those in the open group.There was no significant difference in the score of neck scar scale between the two groups 3 months after surgery(P＞0.05).VAS score of incision satisfaction was(9.08±0.88)in endoscopic group and(8.19±1.30)in open group,and the endoscopic group was better than the open group,the difference was statistically significant(P=0.004).Conclusion For PHPT patients caused by unilateral parathyroid adenoma confirmed through preoperative localization examination,GTAES is a safe and effective surgical approach,which offers unique advantages in intraoperative lesion identification,cosmetic outcomes of the incision,and preservation of anterior neck function,providing a new surgical option for PHPT patients.

Benign prostatic hyperplasia(BPH)is the main reason of causing lower urinary tract symptoms(LUTS)in middle-aged and elderly men,and LUTS can disrupt patients'sleep patterns and interfere with their daily life.With the development of aging,BPH has produced a significant impact on public health,and caused serious social problems and economic burdens.There are various technical approaches for medical devices used in treating BPH,including laser,electrosurgery,focused ultrasound,microwave,stent,and liquid jet removal system,etc.This article summarized the pathogenesis,clinical manifestations,and general overview for guidelines of diagnosis and treatment for BPH.It also reviewed the guiding principle of Food and Drug Administration(FDA)for medical devices used in treating BPH,and focused on analyzing the main contents of non-clinical study,animal study(including animal model,test method,observation time points and evaluation indicators)and clinical study(including selection for control groups,inclusion and exclusion criteria,study endpoint and study duration),so as to provide some enlightenments for the verification,validation and technical evaluation for such products.

Objective To investigate the influence of internet plus diabetes mellitus(DM)shared care model on metabolic profiles and explore its effect in the management of patients with type 1 diabetes mellitus(T1DM).Methods A total of 114 patients with T1DM who were regularly followed up in DM shared care clinic of our hospital more than half a year were enrolled in this study between October 2016 and August 2022.A total of 81 patients who completed the offline assessment of hemoglobin A1c(HbA1c)and other biochemical indicators at the end of 6 months'follow-up,the patients were divided into the standard group(TA,n=42)and the non-standard group(NTA,n=39).HbA1c and other metabolic indexes,chronic complications of DM,weekly average number of logins to the APP(times/week)and duration,weekly number of blood glucose(BG)monitoring sessions,weekly number of dietary monitoring sessions,and weekly number of out-of-hospital communications and duration were evaluated.Logistic regression analysis was used to explore the influencing factors for HbA1c target achievement.Results Compared with the baseline,HbA1c decreased from 7.6%to 6.9%significantly and HbA1c target achievement increased from 33.3%to 51.9%after 6 months of regularly follow-up in the DM shared care model(P<0.05).The weekly average frequency of BG monitoring was higher in the TA group than in the NTA group(P<0.05).Logistic regression analysis showed that the frequency of BG monitoring weeks was the influencing factor of reaching the standard of HbA1c.Conclusions Internet plus DM shared care model could improve HbA1c achievement in patients with T1DM.

Objective:To analyze the perioperative risks and prognosis in patients with differentiated thyroid cancer (DTC) complicated by Graves' disease (GD) .Methods:Clinical data of 880 DTC patients who underwent radical thyroidectomy at the Department of General Surgery, the First Medical Center of Chinese PLA General Hospital between Jan. 2016 and Dec. 2022 was retrospectively collected. The cohort included 119 DTC patients with GD (hyperthyroid group) and 761 DTC patients with normal thyroid function without GD (normal group) . Use propensity score matching (PSM) was used to obtain cohorts with balanced baseline characteristics between the hyperthyroid and normal groups. Perioperative risks and prognos were compared between the two groups.Results:For perioperative risk comparison, after 1∶2 matching, 116 patients were included in the hyperthyroid group and 232 patients in the normal group. The operation time was longer in the hyperthyroid group compared to normal group ([107.26±30.27]min vs. [96.45±32.51]min, P=0.003) . There were no statistical differences between the two groups in intraoperative blood loss, postoperative drainage volume or postoperative hospital stay ( P>0.05) . There were no statistical difference in the incidence of complications such as temporary or permanent hypoparathyroidism, temporary or permanent recurrent laryngeal nerve injury, and lymphatic leakage between the two groups. For prognostic comparison, after 1∶2 matching, 117 cases were included in the hyperthyroid group and 234 cases in the normal group. During follow-up period, 16 patients experienced DTC recurrence, including 5 cases in the hyperthyroid group and 11 cases in the normal group. There was no statistical difference in reccurence-free survival rates between the two groups (5-year RFS: 95.7% vs. 95.3%, P=0.907) . Multivariate Cox regression analysis revealed GD was not the risk factor for DTC recurrence. Conclusions:With standardized and adequate preoperative preparation, the perioperative risks of DTC patients complicated by GD were not increased compared to patients without GD. Additionally, GD does not increase the risk of postoperative tumor recurrence in DTC patients.

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.

AIM:To compare the efficacy and safety of early combination therapy with ranibizumab and dexamethasone intravitreal implants versus ranibizumab monotherapy for the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A retrospective cohort study was conducted on a total of 62 cases(64 eyes)of patients who were first diagnosed with RVO-ME at the Eye Centre of the Affiliated Hospital of Shandong Second Medical University between February 2022 and February 2023. The subjects were divided into two groups according to the different treatment regimens: 32 cases(34 eyes)in the monotherapy group received only ranibizumab [3+pro re nata(PRN)regimen], and 30 cases(30 eyes)in the combination therapy group were injected with ranibizumab once first, followed by dexamethasone intravitreal implant 3 wk later(1+DEX regimen). The best corrected visual acuity(BCVA), central retina thickness(CRT), foveal avascular zone(FAZ)area, macular vascular density(MVD)at the level of the deep vascular complex(DVC)of the retina, the incidence of ocular adverse effects, the number of drug injections, and the total cost between the two groups were compared before and after treatment.RESULTS: At 3 wk, 3 and 6 mo, and at the final follow-up of the two groups of patients, the improvement in BCVA, CRT, and MVD in the DVC layer was significantly better than that before treatment(all P<0.05); there were differences in the comparisons of BCVA and CRT between the two groups at 6 mo and the final follow-up(all P<0.05), and the increase in the number of letters of BCVA was the most pronounced in the combination therapy group at 6 mo of treatment. Statistical significant difference was observed in the comparison of MVD in the DVC layer between the two groups at 3 and 6 mo after treatment and at the final follow-up(all P<0.05). However, no significant change in FAZ area was evident before and after treatment in both groups(P>0.05). The combination therapy group exhibited a reduced number of injections and total cost in comparison to the monotherapy group. The combination therapy group exhibited a slightly higher incidence of high intraocular pressure and cataract progression compared to the monotherapy group, with no statistical significant difference(all P>0.05). Furthermore, no serious adverse events were observed in either group following treatment.CONCLUSION:Compared with ranibizumab alone, ranibizumab combined with dexamethasone intravitreal implant significantly improved vision, reduced macular edema, and lowered the frequency of injections and total treatment cost in patients with RVO-ME. CRT and MVD in the DVC layer are reliable prognostic indicators for patients with RVO-ME.

It is regarded that the disease location of refractory facial paralysis is in the channel sinews of the face， with its primary pathogenesis characterized by a combination of deficiency and stasis of the channel sinews. The integration of repeated shallow needling method and fire acupuncture can first remove stagnation within the channel sinews， and second utilize the warming effect of fire to reinforce yang， stimulate meridian qi， and nourish the channel sinews. This approach balances both supplementation and drainage manipulation， aligning with the underlying pathogenesis of deficiency and stasis combination. In clinical practice， diagnostic methods should be applied flexibly to accurately identify the affected channel sinews. The severity of facial symptoms， the size and mobility of the paralyzed facial muscles， as well as the depth and size of the reactive points identified through palpation， should be considered when determining the extent of the condition. By adjusting the appropriate level of stimulation， the fire acupuncture with repeated shallow needling method could effectively improve facial muscle morphology and function， promoting recovery from the disease.