ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective To analyze the application effect and economic benefit of total parathyroidectomy(TPTX)+subcutaneous implantation of forearm(AT)+thymectomy in patients with secondary hyperparathyroidism(SHPT).Methods The clinical data of 110 patients with SHPT who were treated in our hospital from March 2018 to January 2021 were retrospectively analyzed.They were divided into medication group(50 cases,receiving cinacalcet combined with low-dose calcitriol)and operation group(60 cases,receiving TPTX+AT+thymectomy)according to different treatment regimens.The biochemical indexes,cardiac structure and function,clinical symptoms and quality of life of the two groups were compared before and after treatment for 24 months,and the complications,cost-effectiveness and recurrence rate of the two groups after operation were counted.Results After treatment,the levels of serum iPTH[(206.45±152.59)pg/ml],calcium[(2.05±0.26)mmol/L],phosphorus[(1.48±0.21)mmol/L],calcium-phosphorus product(3.02±0.69)and ALP[(102.03±30.25)U/L]in operation group were all lower Drug group[(721.32±325.36)pg/ml,(2.22±0.18)mmol/L,(1.91±0.22)mmol/L,(4.22±0.74),(140.62±27.15)U/L](P＜0.05);LVEF[(60.85±4.02)％]in operation group was higher than that in drug group[(55.58±3.84)％].LVED[(48.03±2.58)mm]and LVST[(9.85±0.76)mm]were lower than those in drug group[(51.02±3.65)mm,(11.12±0.86)mm](P＜0.05).The scores of bone pain,skin pruritus and restless legs syndrome in the operation group were lower than those of the medication group,and the KDTA score was higher than that of the medication group(P＜0.05).The total cost of treatment in the operation group[(4.06±1.42)million yuan]was not significantly different from that in the drug group[(3.46±1.85)million yuan](P＞0.05).The effective rate of iPTH reduction in operation group was 90.00％(54/60),which was higher than that in drug group(48.00％,24/50)(P＜0.05).The cost-effectiveness analysis showed that the CER of the drug group and the operation group were 7.21 and 4.51 respectively,and the operation treatment had more cost-effectiveness advantages.The incremental cost-effectiveness analysis shows that compared with the drug group,the operation group needs to increase the cost by 14,800 yuan for each additional patient effectively treated for SHPT(P＞0.05).There was no significant difference in the incidence of complications(13.33％VS 12.00％)and the recurrence rate(8.33％VS 4.00％)at 2 4 months after treatment between the operation group and the drug group(P＞0.0 5).Conclusion TPTX+AT+thymectomy can relieve the bone pain,reduce the iPTH level,correct the disorder of calcium and phosphorus metabolism,improve the heart function and structure,and improve the quality of life,and the cost-effectiveness is higher than SHPT of drug treatment,without increasing short-term recurrence rate.

Objective To explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumors.Methods 30 PD-1 humanized mice were selected,and a human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region to construct a human liver cancer transplant tumor model.Tumor-bearing humanized mice were randomly divided into three groups(10 mice per group):① model group(injected with 10 mg/kg of physiological saline),②17-DMAG group(intraperitoneal injection of 17-DMAG at 25 mg/kg,3 times/week),and③cisplatin group(intraperitoneal injection of 20 mg/kg,2 times per week).The experiment lasted for 4 weeks.After injection,the length and shortest diameter of humanized mouse transplanted tumors were measured to calculate the volume,and tumor mass was measured to calculate the tumor inhibition rate.At the same time,immunohistochemical method were used to detect the expression of CD31(tumor microvessel density,MVD)and vascular endothelial growth factor(VEGF)in tumor tissue.Results The tumor volume and mass of the 17-DMAG group and cisplatin group were significantly reduced compared to those of the model group(P＜0.05),and the tumor inhibition rate of the 17-DMAG group was slightly higher than that of the cisplatin group.However,there were no significant differences in tumor mass,volume,and tumor inhibition rate between the 17-DMAG group and cisplatin group.The number of MVD-labeled microvessels and level of VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group(P＜0.05),and those of the 17-DMAG group were also lower than those in the cisplatin group(P＜0.05).Conclusions 17-DMAG can inhibit the growth of humanized mouse liver cancer xenografts by reducing the expression of VEGF in liver cancer xenograft tissue,thereby inhibiting the generation of tumor neovascularization.

Objective:To investigate the efficacy of single locked-plate internal fixation combined with autologous iliac bone graft in the treatment of Rorabeck type II periprosthetic distal femural fracture (PDFF) after total knee arthroplasty (TKA).Methods:A retrospective case series study was made on 13 patients suffering from Rorabeck type II PDFF after primary TKA together with severe osteoporosis (T value≤ -2.5 SD) admitted to 940th Hospital of Joint Logistics Support Force of PLA from January 2016 to December 2020, including 4 males and 9 females, aged 65-85 years [(75.2±6.5)years]. All patients were treated with single locked-plate internal fixation combined with autologous iliac bone graft. Anti-osteoporosis and early standardized joint function rehabilitation were undertaken postoperatively. The operation time and intraoperative blood loss were recorded. The range of motion of knee joint was compared before operation, at postoperative 3, 6 and 12 months and at the last follow-up. The Hospital for Special Surgery (HSS) knee score was assessed at postoperative 3, 6 and 12 months and at the last follow-up to evaluate the recovery of knee joint function. The bone mineral density was reexamined at postoperative 6 months and 12 months to evaluate the therapeutic effect of anti-osteoporosis. Complications were detected as well.Results:All patients were followed up for 12-72 months [(43.2±19.9)months]. The operation time was 90-135 minutes [(103.8±12.6)minutes], with the intraoperative blood loss of 100-250 ml [(150.0±45.6)ml]. The range of motion of knee joint was (114.6±7.8)°, (90.4±8.0)°, (97.3±4.8)° and (98.1±6.3)° before operation and at postoperative 3, 6 and 12 months (all P<0.05). The HSS knee score was (80.2±2.2)points, (84.6±2.9)points and (87.3±3.3)points at postoperative 3, 6 and 12 months (all P<0.05). The knee joint function was excellent in 10 patients and good in 3 at postoperative12 months, and the excellent and good rate was 100%. The T value of bone mineral density was (-3.8±0.6)SD, (-3.4±0.6)SD and (-2.9±0.6)SD preoperatively and at postoperative 6 months and 12 months (all P<0.05). One patient experienced nonunion and was cured after secondary autologous iliac bone grafting combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) bone grafting. Three patients developed venous thrombosis of lower limbs and were cured with oral administration of rivaroxaban. One patient had mild knee flexion and extension limitation and was improved after manual release under femoral nerve block anesthesia and subsequent functional rehabilitation. Conclusion:For patients with Rorabeck type II PDFF after TKA, single locked-plate internal fixation combined with autologous iliac bone graft has advantages of short operation time, few intraoperative bleeding, satisfactory knee range of motion and functional recovery as well as significant improvement of bone mineral density.

【Objective】 To describe the BMI growth trajectories from birth to 24 months and examine the effects of fully breastfeeding time and breastfeeding duration on the BMI growth trajectories. 【Methods】 We conducted a follow-up study of a cohort of 1 388 eligible births. Height and weight were measured at birth, every 3 months to 12 months, and every 6 months to 24 months. Detailed demographic, feeding, activity and diseases data were also collected prospectively. Latent growth mixture modeling was conducted to model the BMI growth trajectories from birth to 24 months. Mixed-effects logistic regression analyses were made to examine the impacts of breastfeeding on this outcome. 【Results】 We identified six BMI trajectory patterns in the 1 285 infants analyzed and labeled them as follows: "normative growth" (26.6%), "normal-accelerating growth" (8.7%), "normal-decelerating growth" (11.7%), "lower-persistent growth" (6.6%), "rapid growth" (26.8%), and "rapid-accelerating growth" (19.5%). Mixed-effects logistic regression analyses revealed that fully breastfeeding ≥ 3 months could significantly decrease the risk of "rapid growth" (OR=0.71, 95% CI 0.51-0.98) and "rapid-accelerating growth" (OR=0.53, 95% CI 0.37-0.75). After adjustment for confounding factors, the relationship remained significant (OR=0.61, 95% CI 0.41-0.89; OR=0.46, 95% CI 0.31-0.68). Weaning before 6 months could significantly increase the risk of "rapid growth" (OR=1.76, 95% CI 1.19-2.61) and "rapid-accelerating growth" (OR=2.08, 95% CI 1.38-3.14). These associations persisted after adjustment for confounding factors (OR=1.69, 95% CI 1.08-2.71; OR=1.88, 95% CI 1.18-2.99). 【Conclusion】 In rural Western China, the main BMI growth trajectory patterns include "normative growth" , "rapid growth" , and "rapid-accelerating growth" . Prolonging breastfeeding may reduce excess weight gain during infancy.

Objective:There are few domestic reports of liver transplantation from schistosomiasis donors. Two schistosomiasis donor livers were employed for liver transplantation. The relevant experiences were summarized along with a literature review.Methods:Two unexpectedly discovered donor livers infected by schistosomiasis were successfully transplanted. And long-term follow-ups were conducted for recipients.Results:The recipients were followed up for 77 and 14 months respectively without recurrence.Conclusions:Non-cirrhotic donor livers infected with schistosome may safely employed for transplantation. A positive donor should be treated with praziquantel. However, a recipient has no indication for preventive deworming.

OBJECTIVE: To assess the reliability and validity of Adversity Quotient Scale in evaluating the adversity quotient among nurses. METHODS: A total of 409 nurses were selected as study subjects from three first-class hospitals in Fujian Province by cluster sampling method. The adversity quotient was investigated by Adversity Quotient Scale and its reliability and validity were tested. RESULTS: The Cronbach′s alpha coefficient, Spearman-Brown coefficient, Guttman Split-Harf coefficient and retest reliability of Adversity Quotient Scale were 0.931, 0.826, 0.823 and 0.940, respectively. The content validity ratio of Adversity Quotient Scale was 0.980. The scores of control, attribution, extension and tolerance factors were positively correlated with the total score of Adversity Quotient Scale(correlation coefficients were 0.813, 0.844, 0.874 and 0.822, respectively, P<0.05). Before model modification, the initial model fitting index of confirmatory factor analysis was χ~2/df=3.72, root mean square residual approximate(RMSEA)=0.09, the overall fitting of the model was not high. After model modification, the combined reliability of control, attribution, extension and tolerance factors were 0.780, 0.796, 0.831 and 0.871, respectively. The fitting index of the modified model was χ~2/df=3.08, RMSEA=0.07, showing a good fitting of the model. CONCLUSION: Adversity Quotient Scale has a good reliability and validity in the assessment of nurses, which can be a reliable and effective adversity quotient assessment tool.