Diabetic nephropathy (DN), as one of the most common complications of diabetes, is a primary cause of end-stage renal disease. The pathogenesis of DN encompasses processes such as chronic inflammation, recruitment and activation of immune cells, tubular and glomerular injury, and renal fibrosis. These processes are highly correlated with the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome and the resulting pyroptosis it mediates. Previous studies have shown that the release of pro-inflammatory cytokines, leakage of damage-associated molecular patterns (DAMPs), recruitment and activation of immune cells can be reduced by regulating the NLRP3 inflammasome and its mediated pyroptosis, thereby slowing the diffusion of inflammatory responses in adjacentcells, fibrosis, and tissue remodeling processes. Ultimately, these process can improve renal injury and dysfunction caused by diabetic nephropathy. This article summarizes the molecular regulatory mechanisms of the NLRP3 inflammasome and its mediated pyroptosis at different pathological stages of DN, proposes potential targets for regulating their activation, aiming to provide a new direction for personalized treatment of DN.

OBJECTIVE: To investigate the effectiveness of free palmaris longus tendon graft reconstruction in the treatment of gouty tophus erosion lesions in flexor tendon of wrist and hand. METHODS: A retrospective analysis was conducted on 8 patients with gouty tophus erosion lesions in flexor tendon of wrist and hand who underwent free palmaris longus tendon graft reconstruction between June 2017 and December 2023. All patients were male, aged 22-65 years, with an average of 45.9 years. The duration of gout history ranged from 2 to 18 years, with an average of 8.8 years. The duration from the discovery of gouty tophus to operation ranged from 12 to 26 months, with an average of 17.6 months. The gouty tophus eroded the flexor pollicis longus tendon in 4 cases, with Verdan flexor tendon zones being Ⅰ-Ⅱ in 1 case and Ⅳ-Ⅴ in 3 cases. The flexor digitorum profundus tendons were affected in 2 cases for the index finger, 1 for the middle finger, and 1 for the ring finger, all located in zone Ⅳ-Ⅴ. The long axis of the gouty tophus ranged from 2.3 to 4.5 cm, with an average of 3.4 cm. All 8 patients presented with limited finger flexion and extension. Among them, 4 cases were accompanied by median nerve compression symptoms, and 1 case had associated bone and joint destruction in the hand. The total active motion (TAM) of the affected finger was (81.3±30.2)° before operation according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, and the functional evaluation was poor. The harvested palmaris longus tendon intraoperatively was 7-9 cm in length. RESULTS: Surgical incisions in all 8 patients healed by first intention, with no infections, graft non-union, or significant adhesion complications. All patients were followed up 8-25 months, with an average of 14.8 months. Numbness symptoms resolved in all 4 patients who presented with median nerve compression symptoms. Patients did not experience wrist pain or other discomfort, and function was not compromised. At last follow-up, according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, the TAM of 8 patients was (197.5±55.8)°, which significantly improved when compared with that before operation ( t=11.638, P<0.001); the hand function of 1 patient with gouty tophus in zone Ⅰ-Ⅱ flexor pollicis longus tendon was good, and the other 7 patients were excellent. CONCLUSION Free palmaris longus tendon graft reconstruction demonstrates good effectiveness in treating gouty tophus erosion lesions in flexor tendon of wrist and hand.
Humans ; Middle Aged ; Male ; Adult ; Tendons/surgery* ; Retrospective Studies ; Aged ; Gout/complications* ; Wrist/surgery* ; Plastic Surgery Procedures/methods* ; Hand/surgery* ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the effectiveness of multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repair of amputated palm injury distal to the superficial palmar arch. METHODS: Between September 2018 and July 2023, 5 patients with amputated palm injury distal to the superficial palmar arch were treated. There were 3 males and 2 females with an average age of 35.4 years (range, 29-52 years). The time from injury to admission was 1-6 hours (mean, 3.2 hours). The multi-segment inverted Y-shaped vein transplantation in the anterior lateral malleolar venous network were used to repair the common and proper palmar digital arteries; the another anterior lateral malleolar venous network was used to repair the dorsal vein of the hand. The soft tissue defect of dorsal hand in 1 patient was repaired with the pedicled ilioinguinal flap, and the wound at the donor site was directly sutured. Postoperative treatment included anti-infection therapy, antispasmodic therapy, and thrombosis prevention measures. RESULTS: The partial necrosis of the fingertip of the thumb occurred in 1 case, and the marginal necrosis of the abdominal flap after operation occurred in 1 case. The remaining fingers showed good blood supply with normal tension. The incision at donor site of the abdominal flap healed by first intention. All patients were followed up 8-41 months (median, 19 months). At last follow-up, the hand contour was satisfactory; the grasping function, opposition function, and proprioception recovered, and two-point discrimination ranged from 5 to 7 mm (mean, 6 mm). According to the upper extremity function evaluation criteria issued by Hand Surgery Society of the Chinese Medical Association, the functional outcomes were excellent in 3 cases, good in 1 case, and fair in 1 case. CONCLUSION The multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repairing defects in the common and proper palmar digital arteries distal to the superficial palmar arch offers advantages such as superficial location, flexible harvesting, and high compatibility. This technique has demonstrated favorable outcomes in complex transmetacarpal amputation reconstruction.
Humans ; Adult ; Male ; Female ; Hand Injuries/surgery* ; Middle Aged ; Plastic Surgery Procedures/methods* ; Veins/transplantation* ; Surgical Flaps/blood supply* ; Hand/surgery* ; Treatment Outcome ; Soft Tissue Injuries/surgery*

OBJECTIVE: To explore the effectiveness of the flexor digitorum longus (FDL) transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy in the treatment of stage ⅠAB progressive collapsing foot deformity (PCFD). METHODS: Between January 2019 and September 2023, 19 patients (19 feet) with stage ⅠAB PCFD were treated with FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy. There were 11 males and 8 females, aged 18 to 60 years, with an average age of 45.5 years. Nine cases were on the left foot and 10 cases on the right foot. The disease duration was 9-21 months, with an average of 12.3 months. Postoperatively, the effectiveness was evaluated by visual analogue scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Tegner score. Based on X-ray films, the talonavicular coverage angle (TNCA), talus-first metatarsal angle (T1MT), Meary angle, and pitch angle were measured. The plantar pressure parameters of the foot were measured by the Footscan plantar pressure measurement system, including peak pressure and load of the forefoot, midfoot, and hind foot. The patients' satisfaction with the surgical outcome was evaluated. RESULTS: All 19 surgeries were successfully completed. One patient had poor incision healing after operation, while the incisions of the remaining patients healed by first intention. All patients were followed up 12-28 months (mean, 16.8 months). At last follow-up, the VAS score significantly decreased compared with that before operation, and the AOFAS score and Tegner score significantly increased ( P<0.05). Radiological measurements showed that the TNCA, T1MT, Meary angle, and Pitch angle all significantly improved compared with those before operation ( P<0.05). Plantar pressure tests indicated that the peak pressures of the forefoot and midfoot significantly reduced compared with those before operation ( P<0.05), while the peak pressure of the hind foot showed no significant change ( P>0.05). The forefoot load significantly increased and the midfoot load decreased compared with those before operation ( P<0.05), while the hind foot load showed no significant change ( P>0.05). The total satisfaction rate of patients with the surgical outcome (very satisfied+satisfied) reached 84.2% (16/19). CONCLUSION The FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy can effectively correct the stage ⅠAB PCFD, improve the abnormal distribution of plantar pressure and load, alleviate foot pain symptoms, and improve foot movement function. The patient's satisfaction is high. However, the long-term effectiveness still needs to be further observed and clarified.
Humans ; Female ; Male ; Osteotomy/methods* ; Adult ; Middle Aged ; Calcaneus/surgery* ; Young Adult ; Adolescent ; Tendon Transfer/methods* ; Treatment Outcome ; Plastic Surgery Procedures/methods* ; Foot Deformities/surgery* ; Ligaments, Articular/surgery*

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

Objective:To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition.Methods:Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10 7 IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results:Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time ( Z=-7.138, P<0.001), γ-glutamyltransferase ( t ?=-2.940, P=0.004), aspartate aminotransferase ( t ?=-2.749, P=0.007), ALT ( t ?=-2.153, P=0.033), HBV DNA level ( t ?=-4.771, P=0.010) and portal vein inner diameter ( t ?=-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval ( CI): 1.267-1.630; P<0.001)] and portal vein inner diameter ( OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion:A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P＜0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P＜0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P＜0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P＜0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P＜0.05).The patients with high expression of GLIS3 had significant shorter disease-free survival time than those with low expression(P＜0.05),but had no statistical difference in overall survival(P＞0.05).Conclusion GLIS3 protein is highly expressed in TNBC tissues,and tumor size and TNM stage are correlated with its high expression.The high expression of GLIS3 suggests that the patients have poor prognosis and low disease-free survival rate.