This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

OBJECTIVE: To explore the application effect of grid locator in hip arthroscopy for the treatment of femoral acetabular impingement (FAI). METHODS: Total of 50 patients of FAI were treated by arthroscopic hip joint surgery for from January 2020 to January 2021, and were divided into two groups according to intraoperative positioning methods. Among them, 27 cases in the positioner group were treated by hip arthroscopy assisted by grid positioner including 10 males and 17 females with a mean age of (35.91±9.92) years old. In the non-locator group, 23 cases were treated with hip arthroscopy by positioning puncture according to the operator's experience including 12 males and 11 females with a mean age of (36.01±11.03) years old. Intraoperative fluoroscopy times, puncture time, adjusted puncture times and operation time of two groups were compared. The α Angle and lateral central edge(LCE) angle of hip joint were measured and compared before and after operation. Four evaluation indexes were recorded and compared, including pain visual analogue scale(VAS), hip Harris score, non-inflammatory hip joint score (NAHS), hip joint activities of daily living (HOS-ADL). RESULTS: All patients were followed up for 6 to 12 months with an average of (18.69±3.72) months. The α angle and LCE angle of hip joint at 1 month after operation were decreased in both groups(P<0.05), but there was no significant difference between groups(P>0.05). VAS, hip Harris score, NAHS and HOS-ADL score after operation were higher than those before operation(P<0.05), but there was no statistical significance between groups (P>0.05). Intraoperative fluoroscopy times(6.04±1.13), puncture time(13.19±3.52) min, puncture adjustment times(4.59±1.55) and operation time(48.28±3.38) min in the positioner group were less (shorter) than those of (13.43±2.56), (22.39±2.93) min, (10.43±3.33), (62.25±5.73) min in the non-positioner group(P<0.05). No postoperative complications occurred in both groups, and the pain was significantly relieved. CONCLUSION The application of hip arthroscopy in the treatment of femoral acetabular impingement sign can obtain good postoperative results. Compared with the traditional positioning method, the grid locator can improve the accuracy of skin positioning point, shorten the puncture time, reduce the number of fluoroscopy, and improve the efficiency of surgical puncture.
Humans ; Male ; Female ; Arthroscopy/instrumentation* ; Femoracetabular Impingement/physiopathology* ; Adult ; Middle Aged ; Hip Joint/surgery*

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective To compare the dosimetric differences in the heart and its substructures between two hybrid plans for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. Methods A total of 46 patients with early-stage left-sided breast cancer who underwent hypofractionated whole-breast radiotherapy were randomly selected. Two hybrid radiotherapy plans were used, including hybrid intensity-modulated radiotherapy (H_IMRT) and hybrid volumetric-modulated arc therapy (H_VMAT). The heart and its substructures were contoured, including left anterior descending (LAD), left ventricle (LV), right coronary artery (RCA), and right ventricle (RV). The heart and substructure doses, as well as monitor units, were compared between H_IMRT and H_VMAT. Results Both hybrid plans met the clinical requirements. H_IMRT significantly outperformed H_VMAT for the heart (V₁₀, V₃₀, and D_mean), LAD (V₃₀, V₄₀, D_max and D_mean), LV (V₁₀, V₂₀ and D_mean), RCA (D_max, D_mean), and RV (V₅, V₁₀, D_mean) (P < 0.001). Additionally, H_IMRT was significantly superior to H_VMAT for heart V₅, LAD V₂₀, and RV V₂₀ (P = 0.005, 0.035 and 0.037). For LAD (V₁₅, V₄₀) and LV (V₅, V₂₅), H_IMRT was slightly better than H_VMAT, and the difference was not statistically significant. Conclusion Both H_IMRT and H_VMAT hybrid radiotherapy plans are suitable for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. H_IMRT is slightly better than H_VMAT in dose sparing for the heart and its substructures.

Progesterone receptor membrane component 1(PGRMC1)is closely related to hormone therapy which belongs to the membrane-associated progesterone receptor(MAPR)family.A large number of in vitro experiments,in vivo animal experiments,clinical samples of breast cancer patients and blood studies showed that all synthetic progesterone(excluding natural progesterone and dydrogesterone)can promote the rapid proliferation of breast cancer cells overexpressing PGRMC1.In patients with breast cancer,PGRMC1 is significantly negatively correlated with tumor grade and prognosis,and PGRMC1 level in blood is positively correlated with PGRMC1 expression in breast cancer tissues,and PGRMC1 is superior to traditional tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen(CA125),and CA153 in predicting early breast cancer.Therefore,PGRMC1 may serve as a predictive marker for identifying an elevated risk of breast cancer associated with menopausal hormone replacement therapy.

Background and Aims:Medullary thyroid carcinoma(MTC)is an aggressive malignancy that is frequently associated with cervical lymph node metastasis,significantly affecting patient prognosis.However,the risk factors for lateral cervical lymph node metastasis(LLNM)in MTC remain inconclusive.This study aims to identify the risk factors associated with LLNM in MTC patients,in order to inform individualized surgical decision-making.Methods:The clinicopathologic data of 242 patients with MTC who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from 2011 to 2019 were retrospectively collected.The relationships between preoperative tumor markers,including calcitonin and carcinoembryonic antigen(CEA),and LLNM were evaluated.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for LLNM.Results:Preoperative calcitonin level was significantly associated with tumor diameter,the number of lymph node metastases,and the extent of lymph node involvement,while preoperative CEA level was significantly associated with tumor diameter(all P<0.05).The area under the ROC curve for preoperative calcitonin in diagnosing LLNM was 0.750(P=0.000),with an optimal cutoff value of 266.00 ng/L(sensitivity 0.854,specificity 0.577).The diagnostic value of preoperative CEA for LLNM was limited.Univariate analysis showed that sex,extracapsular extension,T stage,central lymph node metastasis(CLNM),bilateral lesions,preoperative calcitonin,tumor diameter,and multifocality were significantly associated with LLNM in MTC patients(all P<0.05).Multivariate analysis revealed that CLNM(OR=17.645,95%CI=7.728-40.290)and preoperative calcitonin≥266.00 ng/L(OR=7.832,95%CI=3.132-19.582)were independent risk factors for LLNM.Conclusion:CLNM and elevated preoperative calcitonin level are closely associated with LLNM in patients with MTC.The combination of these two indicators may help identify high-risk patients for LLNM,thereby and promoting individualized and precise treatment strategies for MTC.

In recent years,more and more researches has focused on the correlation between cognitive activity and physiological variables.The change of pupil is regarded as an important target in the cognitive process,and has become a hot research field.This review focuses on the three key brain regions that regulate pupil change,and reflects the neurophysiological mechanism behind pupil change by elaborating the neural pathways related to pupil change and cognitive performance.Based on recent studies on pupil change in cognitive diseases,it aims to promote the application of pupil change in the field of cognitive science in the future.

Objective To investigate the therapeutic effects and mechanisms of dexmedetomi-dine and remimazolam on neuropathic pain.Methods A total of 60 SD rats were divided into sham operation group(n=12),spinal nerve ligation(SNL)+NC group(n=12),SNL+DEX group(n=12),SNL+REM group(n=12)and DEX+REM group(n=12).Mechanical withdrawal threshold(MWT)was analyzed in each group.The expression level of pain-related protein c-Fos was detected by Western blot.Autophagy was assessed by immunofluorescence analysis.Enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6)and interleukin-10(IL-10)]of each group.The expression level of oxidative stress factor in each group was ana-lyzed.The expression levels of NFE2L2/NRF2 pathway related proteins were analyzed by Western blot.Results MWT in the SNL+DEX,SNL+REM and DEX+REM groups was significantly high-er than that in the SNL+NC group(P＜0.05).The expression level of c-Fos protein in the SNL+NC group was significantly higher than that in the SNL+DEX,SNL+REM and DEX+REM groups(P＜0.05).The immunofluorescence intensity of LC3 and NeuN in SNL rats was lower than that in sham operation rats,indicating that autophagy of neurons in SNL rats was damaged.The immunofluorescence intensity of LC3 and NeuN in the SNL+DEX group,SNL+REM group and DEX+REM group were significantly higher than those in the SNL+NC group(P＜0.05).The expression levels of TNF-α,IL-1 β and IL-6 in the SNL+DEX group,SNL+REM group and DEX+REM group were signifi-cantly lower than those in the SNL+NC group(P＜0.05).Glutathione(GSH)and catalase(CAT)levels in the SNL+DEX,SNL+REM and DEX+REM groups were significantly higher than those in the SNL+NC group,while malondialdehyde(MDA)levels were significantly lower(P＜0.05).The expression levels of NFE2L2 protein in the SNL+DEX,SNL+REM and DEX+REM groups were significantly lower than that in the SNL+NC group,with the lowest level observed in the DEX+REM group(P＜0.05).Conclusion Dexmedetomidine and remimazolam can re-lieve neuropathic pain in SNL rats by inhibiting the expression of NFE2L2/NRF2 pathway-related proteins and decreasing oxidative stress levels.

Objective:To explore the diagnostic value of shear wave elastography(SWE)for clinically significant prostate cancer(csPCa).Methods:We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer(PCa)in Baoji Central Hospital from June 2017 to July 2023.All the patients underwent the following examinations in the order of serum prostate-spe-cific antigen(PSA)testing,transrectal ultrasonography(TRUS),measurement of the stiffness of the entire prostate gland by SWE,and TRUS-guided prostate puncture biopsy.The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base,middle,and apex of the prostate,including the maximum Young's modulus(Emax),mean Young's modulus(Emean),and minimum Young's modulus(Emin).We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results,focusing on their diagnostic performance for csPCa.Results:Of the 359 cases,189 were diag-nosed by pathological puncture biopsy as BPH,26 as non-csPCa,and 144 as csPCa.The PSA level,Emax,Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups(all P＜0.01),but showed no statistically significant difference between the BPH and non-csPCa groups(all P＞0.05).The area under the receiver operating characteristic curve(AUC),optimal cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accura-cy of Emax in the diagnosis of csPCa were 0.852,143.92 kPa,72.22％,84.65％,75.91％,81.98％and 79.67％;those of Emean were 0.868,82.42 kPa,67.36％,91.16％,83.62％,80.66％and 81.62％;and those of Emin were 0.682,32.73 kPa,47.22％,89.30％,73.91％,71.54％and 72.14％,respectively.In the non-csPCa group,Emax,Emean and Emin were found be-low the optimal cut-off value in 73.08％(19/26),92.31％(24/26)and 88.46％(23/26),respectively.Conclusion:The stiff-ness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa,reduces unnecessary detection of non-csPCa,and provides some reference for its active surveillance.