BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

BackgroundPatients with depressive episode and schizophrenia have a high risk of suicide. The sleep electroencephalogram power spectral density characteristics of patients with depressive episode accompanied by suicidal behavior and those with schizophrenia may be different， but there is currently a lack of direct comparative studies on these two groups of patients. ObjectiveTo compare the sleep electroencephalogram power spectral density between depressive episode and schizophrenic patients with suicidal behavior， in order to provide references for exploring predictive indicators of suicidal behavior. MethodsFrom June 2018 to December 2020， 20 patients with depressive episode and 20 patients with schizophrenia who had committed suicide within the past month and were treated at the outpatient department of Shenzhen Kangning Hospital were selected. All of them met the diagnostic criteria for depressive episode or schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）. Using a random sampling method， 20 volunteers with matching gender and age to the patient groups were selected from the Cuiping community in Shenzhen as the control group. The subjective sleep of the patients was evaluated using the Insomnia Severity Index （ISI）， the Dysfunctional Belief and Attitude about Sleep （DBAS）， the Disturbing Dreams and Nightmare Severity Index （DDNSI）， and the Epworth Somnolence Scale （ESS）. The objective sleep of the patients was assessed using polysomnography. The sleep electroencephalogram was filtered and the power spectral density of the brain wave was analyzed and processed for all the subjects. The subjective and objective sleep conditions of the two patient groups were compared， and the sleep electroencephalogram power spectral density of the patient groups and the control group were also compared. ResultsA comparison of subjective and objective sleep conditions between patients with depressive episode accompanied by suicidal behavior and patients with schizophrenia accompanied by suicidal behavior showed no statistically significant differences （P>0.05）. Comparisons of sleep electroencephalogram power spectral density in the W stage （average power of α wave， total power of δ wave， average power of δ wave， average power of θ wave）， N1 stage （average power of β wave， total power of α wave， total power of δ wave）， N2 stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave）， N3 stage （average power of α wave， average power of δ wave）， and R stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave） between patients with depressive episode accompanied by suicidal behavior， patients with schizophrenia accompanied by suicidal behavior， and the control group showed statistically significant differences （P<0.05 or 0.01）. The total power of δ wave in the W stage and the average power of β wave and δ wave in the N1 stage were higher in two patient groups were higher than those of the control group. The total power of α wave and the average power of α wave in the N2 stage were lower than those of the control group， while the average power of δ wave was higher than that of the control group. The average power of α wave in the N3 stage of both patient groups were lower than that of the control group， while the average power of δ wave was higher than that of the control group. The total power and average power of α wave in the R stage were lower than those of the control group， while the total power and average power of δ wave were higher than those of the control group. All the differences were statistically significant. Patients with depressive episode accompanied by suicidal behavior had higher average powers of α wave， δ wave， and θ wave in the W stage compared with the control group， while the total power of α wave in the N1 stage was lower in the former group. All these differences were statistically significant （P<0.05）. ConclusionThe depressive episode patients accompanied by suicidal behavior have highly overlapping sleep electroencephalogram abnormal patterns with those of schizophrenia patients， mainly manifested as a general decrease in α wave power （N2， N3， R stage） and a general increase in δ wave power （W， N1， N2， N3， R stage） as well as β wave power in N1 stage. At the same time， patients with depressive episode accompanied by suicidal behavior also show specific changes， including an increase in the average power of α and θ waves during the wakefulness period （W stage）， and a decrease in the total power of α wave in N1 stage. ［Funded by Guangdong Province High-level Clinical Key Specialty （with supporting funds from Shenzhen City） （number， SZGSP013）； Shenzhen Key Medical Discipline （number， SZXK041）； Shenzhen Clinical Medicine Research Center Project （number， 20210617155253001）］

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Pathologic myopia(PM)is characterized by progressive axial elongation, posterior staphyloma, and fundus degenerative changes, representing a leading cause of blindness in Asian countries.Posterior scleral reinforcement(PSR)is currently the only surgical intervention to slow axial elongation. Its mechanisms involve mechanical reinforcement, improved blood circulation, and biological stimulation of scleral remodeling. This article reviews recent advances in PSR: surgical techniques have evolved from complex, classic procedures to standardized single-strip methods, incorporating 3D MRI to quantify posterior staphyloma morphology for personalized graft design and facilitating minimally invasive, precision surgery. Among implant materials, biomaterials such as allogeneic dura mater are being continuously optimized, while biomimetic piezoelectric smart materials actively promote scleral collagen synthesis through electrical signals, achieving a paradigm shift from “passive support”to “active reinforcement”. Clinical outcomes indicate advantages in regulating axial length, enhancing visual function and blood circulation, and facilitating early intervention in children. Combined procedures with ICL implantation, cataract surgery or vitrectomy provide comprehensive treatment regimens for individual patients with varied conditions. This article also analyzes long-term issues and core controversies including ectopic posterior staphyloma and reoperation, and prospects future research directions such as artificial intelligence assistance, translation of smart materials and full-cycle prevention and treatment systems, so as to provide references for clinical practice and scientific research.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

Objective:The Social Isolation Scale for people with type 2 diabetes mellitus (T2DM) was developed and tested for reliability and validity, which provided an effective tool for measuring the social isolation level of patients with T2DM.Methods:The initial scale was developed through literature review, qualitative interviews, and expert consultation. Convenience sampling method was used to select T2DM patients who met the inclusion and exclusion criteria for questionnaire survey. The item analysis method was used to select the items of the scale. Exploratory and confirmatory factor analyses were used to evaluate construct validity. The content validity of the scale was evaluated by the scale-level content validity index and the item-level content validity index. The criterion validity was verified by using the Lubben Social Network Scale-6 and the De Jong Gierveld Loneliness Scale. Reliability was tested through internal consistency and test-retest reliability.Results:Through literature review and qualitative interviews, 30 items of the scale were selected to form the first version scale. After two rounds of inquiries from 16 experts (expert authority coefficient = 0.897), the second version of the scale was formed. A total of 407 questionnaires were distributed in two stages using the second version scale. Among the 407 patients, there were 214 males and 193 females. Exploratory factor analysis extracted 4 common factors, with a cumulative variance contribution rate of 61.338%. The final scale was determined to include 4 dimensions and 16 items, with the dimensions being "social support network", "frequency of social participation", "satisfaction with interpersonal relationships", and "diabetes-related sense of isolation".The average content validity index at the scale level was 0.929, the content validity index at the item level was 0.830 - 1.000, and the criterion validity was - 0.647 and 0.681. The Cronbach′s α coefficient of the total scale was 0.822, and the test-retest reliability was 0.858.Conclusions:The Social Isolation Scale for people with T2DM has good reliability and validity. It is a reliable and valid tool for assessing social isolation in T2DM patients.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
Humans ; Parkinson Disease/drug therapy* ; Diabetes Mellitus, Type 2/pathology* ; Signal Transduction/physiology* ; Receptor, Insulin/metabolism* ; Animals ; Insulin Resistance/physiology* ; Insulin/metabolism*