ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective: To examine the mediating effect of resilience on AIDS-related stress and patient-reported outcome among elderly cases with HIV/AIDS, so as to provide the basis for promoting mental health and improving health outcomes of this population. Methods: From June to July 2024, elderly cases with HIV/AIDS receiving treatment in the infectious diseases department of a tertiary-level hospital in Sichuan Province and undergoing follow-up management at 12 community health service centers in Wuhou District, Chengdu City, Sichuan Province, were selected as study participants using convenience sampling method. Data on demographic information, duration since confirmed diagnosis and the most recent CD4+T lymphocyte count were collected through questionnaire surveys. The Chinese versions of the HIV/AIDS Stress Scale, the Chinese versions of the 10-item Connor-Davidson Resilience Scale, and the Patient-Reported Outcome Scale for Elderly HIV/AIDS Patients were used to assess AIDS-related stress, resilience, and patient-reported outcome, respectively. Structural equation modeling was performed using Mplus 8.3 software to analyze the mediating effect of resilience on AIDS-related stress and patient-reported outcome. The Bootstrap method was employed to test the significance of the mediating effect. Results: A total of 424 elderly HIV/AIDS cases were included, with a mean age of (62.04±8.73) years. Among them, 315 (74.29%) were males and 109 (25.71%) were females. The median scores were 23.00 (interquartile range, 11.00) points for AIDS-related stress, 30.00 (interquartile range, 7.00) points for resilience, and 363.45 (interquartile range, 53.03) points for the total score of patient-reported outcome. Resultsof the mediation effect analysis revealed that AIDS-related stress had a direct negative effect on patient-reported outcome (β=-0.608, 95%CI: -0.742 to -0.465). It also exerted an indirect negative effect on patient-reported outcome through the mediating role of resilience (β=-0.258, 95%CI: -0.364 to -0.158), with the mediating effect accounting for 29.79% of the total effect. Conclusion AIDS-related stress among elderly cases with HIV/AIDS can directly or indirectly negatively affect patient-reported outcome through resilience.

OBJECTIVE To study the intervention effects of Wenshen Tongluo Zhitong Recipe(WTZR)on macrophage senes-cence and senile osteoporosis.METHODS The senescent macrophage model was established using hydrogen peroxide(H2 O2)and subsequently divided into four groups:control,model,low-dose drug-treated serum,and high-dose drug-treated serum.β-galactosidase staining,Western blot and qPCR were employed to evaluate the mRNA expression of senescence markers p21 and p53.ROS staining and JC-1 staining were applied to assess mitochondrial function in macrophages.The mRNA levels of Interleukin(IL)-6,IL-10,CD206,and inducible nitric oxide synthase(iNOS)were determined by qPCR analysis.Immunofluorescence was used to evaluate argi-nase(ARG1)and iNOS protein expressions for assessing the impact of drug-containing serum on macrophage polarization.qPCR analy-sis was conducted to measure osteocalcin(OCN),collagen type Ⅰ alpha 1(Col1a1),runt-related transcription factor 2(Runx2)mRNA levels as osteoblast-related markers;ALP staining along with alizarin red staining were performed to evaluate the effect of macrophage conditioned medium treated with drug-containing serum on bone marrow mesenchymal stromal cell(BMSC)osteogenic differentiation.C57BL/6J mice were randomly allocated into four groups:control group,model group,WTZR low-dose group,and WTZR high-dose group.The senile osteoporosis(SOP)mouse model was established by D-galactose.Micro-CT scanning analyzed fe-mur microstructure while HE staining detected pathological changes in femur bone tissue samples collected from each experimental con-dition.Furthermore,Western blot was used to detect the senescence-related molecules p21 and p53 and the osteogenesis-related mark-ers OCN and Runx2,qPCR analysis measured tibial expression levels of senescence-related molecules(p21,p53)as well as macro-phage polarisation-related molecules(IL-6,iNOS,CD206,and IL-10)to assess the effect of this compound on a mouse model simula-ting SOP.RESULTS Following intervention with serum containing WTZR,there was a significant decrease in the number of senes-cent positive cells compared to the model group.Additionally,there was a notable decrease in p21 and p53 mRNA and proteins expres-sion(P＜0.05,P＜0.01,P＜0.001).Furthermore,drug-containing WTZR effectively inhibited ROS production induced by H2 O2 and mitigated mitochondrial membrane potential reduction in macrophages(P＜0.05,P＜0.001).Treatment with drug-containing WTZR re-sulted in down-regulated mRNA expression of M1-related gene iNOS(P＜0.05)while up-regulating mRNA expression of M2-related genes CD163 and CD206(P＜0.05).The drug-containing WTZR significantly reduced fluorescence intensity for iNOS(P＜0.01)while increasing ARG1(P＜0.05)fluorescence intensity.Moreover,conditioned medium from macrophages treated with drug-containing ser-um increased ALP positive cell count(P＜0.01,P＜0.001),alizarin red positive area(P＜0.05),as well as Col1a1,Runx2 and OCN mRNA expression levels(P＜0.05,P＜0.01).The Tb.N,BMD,and BV/TV were significantly higher in the WTZR group compared to the model group(P＜0.05,P＜0.01,P＜0.001);meanwhile,Tb.Sp was notably lower than that observed in the model group(P＜0.05,P＜0.01);bone trabeculae were significantly improved,increased in number and widened.Additionally,the compound could significantly inhibit the D-galactose induced up-regulation of tibial senescence-related genes and proteins p21 and p53(P＜0.05,P＜0.001,P＜0.0001),promote the expression of osteogenesis-related markers OCN and Runx2 protein(P＜0.01,P＜0.0001),promote the down-regulation of M1 related genes IL-6 and iNOS(P＜0.05),and promote the expression of M2 related genes IL-10 and CD206(P＜0.05,P＜0.01).CONCLUSION Wenshen Tongluo Zhitong Recipe may play an anti-osteoporosis effect by inhibiting macrophage senescence and promoting the osteogenic differentiation of BMSC.

Objective:To investigate the impact of rosacea on patients＇ quality of life and mental health, and to analyze variations across different subtypes, gender, sun exposure, smoking status, ethnicity, and educational levels, as well as patients＇ demands for treatment.Methods:It was a cross-sectional study from October 2022 to January 2024, 177 rosacea patients from the Department of Dermatology, the First Affiliated Hospital of Kunming Medical University were surveyed. The cohort comprised 36 males and 141 females, with a median age of 35 (29, 44) years. Data collected through questionnaires included general information, Dermatology Life Quality Index (DLQI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Patient Need Questionnaire (PNQ). Statistical analysis was conducted on the collected data.Results:The median DLQI score was 10 (3, 15), indicating moderate impact. The median GAD-7 score was 5 (2, 7), suggesting mild anxiety; while the median PHQ-9 score was 6 (2, 9), indicating mild depression. Female patients scored higher in both DLQI and GAD-7 than males ( P<0.05). Papulopustular subtypes had higher DLQI and GAD-7 scores compared to other subtypes ( P<0.01). Patients with lower education levels scored higher in DLQI and GAD-7 than those with higher education ( P<0.01), and non-smokers had higher GAD-7 scores than smokers ( P<0.05). Significant positive correlations were found between DLQI and PHQ-9 ( r=0.39, P<0.01), and DLQI and GAD-7 ( r=0.51, P<0.01), as well as between PHQ-9 and GAD-7 ( r=0.59, P<0.01). Regarding treatment needs, 159 patients (89.8%) expressed a strong desire for a clear diagnosis and treatment plan, and the same number wished for a complete resolution of all skin lesions. Female patients consistently demonstrated significantly stronger demands in all 28 treatment need items (all P<0.05). Conclusions:Rosacea significantly affects patients＇ quality of life and mental health, particularly among females, individuals with papulopustular subtypes, and those with lower education levels. There is a strong demand for definitive diagnostic and therapeutic plans, especially among female patients.

Objective To observe and compare of the effects of esketamine and sufentanil induction for general anesthesia on postoperative analgesia in obese patients undergoing laparoscopic sleeve gastrectomy.Methods Patients scheduled for elective laparoscopic sleeve gastrectomy between March 2023 and March 2024,irrespective of gender,aged between 20 and 50 years,with a BMI ranging from 30.0 to 50.0 kg/m2 and ASA Ⅰ or Ⅱ classification,were randomly allocated into two groups:the esketamine group(Group E)and the sufentanil group(Group S),each consisting of 32 cases.During anesthesia induction,Group E received a dose of esketamine at 0.5 mg/kg while Group S received sufentanil at a dosage of 0.5 μg/kg;the remaining protocol remained unchanged.Heart rate(HR),mean arterial pressure(MAP),and SpO2 were recorded at various time points:upon arrival(T0),prior to anesthesia induction(T1),immediately after induction(T2),during intubation(T3),at the conclusion of anesthesia adminis-tration(T4),and during extubation(T5).Postoperative pain scores using the Numeric Rating Scale(NRS)were assessed at specific intervals following surgery:one hour post-surgery(P0),six hours post-surgery(P1),twelve hours post-surgery(P2),twenty-four hours post-surgery(P3)and forty-eight hours post-surgery(P4).Additionally,intraoperative remifentanil consumption as well as the number of presses on the analgesic pump within forty-eight hours after surgery in both patient groups were documented along with any occurrences of adverse reactions.Results During the surgery,there was no statistically significant difference in mean arterial pressure(MAP)and heart rate(HR)between the two patient groups at T0～T5(P>0.05).At T2,both groups exhibited lower MAP and HR compared to T0;specifically,group S had a MAP of(91.81±8.94)mmHg and HR of(81.75±13.37)beats/min,while group E had a MAP of(93.69±9.96)mmHg and HR of(80.38±13.2)beats/min,with group E showing values closer to baseline levels.At T3,both groups experienced a transient increase in MAP and HR(P<0.05);specifi-cally,group S had a MAP of(97.56±8.96)mmHg and HR of(86.47±13.84)beats/min,while group E had a MAP of(101.03±8.29)mmHg and(89.41±15.32)times/min,with S group closer to baseline values.There was no statistically significant difference in the amount of remifentanil used during surgery between group S and group E(P>0.05),which were(2071.88±717.63)μg and(2093.75±718.39)μg,respectively.Compared with the postoperative conditions of the two groups,the NRS scores of group E(0.41±0.61±1.870.75,2.47±0.62)at P0,P1 and P2 were lower than those in group S(0.88±0.71,2.47±0.72,2.97±0.54),and the difference was statisti-cally significant(P<0.05).The number of intravenous analgesia pump presses was significantly reduced in group E after surgery(P<0.05),with the postoperative analgesic pump compressions occurring 11.25±2.70 times in group S and 8.56±2.23 times in group E.The incidence of postoperative nausea and vomiting(PONV)and hypotension in Group E(21.88%,15.63%)was lower than that observed in group S(46.88%,37.50%),demonstrating statistical significance(P<0.05).Conclusion In comparison to sufentanil induction,the utilization of esketamine anesthesia induction is deemed safe for laparoscopic sleeve gastrectomy in obese patients,effectively mitigating postoperative acute pain and reducing the incidence of PONV.

Objective To explore the protective effects and the underlying mechanisms of bone marrow mesenchymal stem cells(BMSCs)on the brain in microgravity environment.Methods The physiological effects of microgravity were simulated with the hindlimb unloading(HU)mouse model.The animals were divided into 3 groups:the control group(wild-type mice),the hindlimb unloading(HU)group,and the BMSCs treatment group,with six in each.RT-qPCR was adopted to determine the expression levels of pro-inflammatory cytokines(Il-6,Il-1β and Tnf-α)in the cerebral cortex;immunohistochemistry was performed to evaluate the proportions of microglia(IBA-positive)and astrocytes(GFAP-positive);Western blot was used to measure the expression levels of apoptosis-and senescence-related molecules(BAX,BCL-2,p21,and p53).Results Compared with wild-type mice,the expression levels of Il-6,Il-1β and Tnf-α in the cerebral cortex of HU mice were significantly increased(P＜0.05),the expression level of BAX,p21 and p53 was also significantly increased(P＜0.05).However,the expression level of BCL-2 protein were significantly decreased(P＜0.05).The proportion of micro-glia(IBA1 positive)and astrocytes(GFAP positive)was increased(P＜0.05);After BMSCs treatment,the expression level of Il-1β in the cerebral cortex of HU mice was significantly decreased(P＜0.05),the expression levels of BAX,p21 and p53 were significantly decreased(P＜0.05),and the expression level of BCL-2 protein was significantly increased(P＜0.05).The proportion of microglia(IBA1 positive)and astrocytes(GFAP posi-tive)decreased(P＜0.05).Conclusions BMSCs potentially relieve the detrimental effects of simulated micro-gravity on mouse brain by inhibiting inflammation,apoptosis and cellular senescence.

Genicular nerve block is usually used for the treatment of chronic pain of knee osteoar-thritis,which can effectively relieve knee pain and preservemotor function.With the rapid development of ultrasound technology,ultrasound-guided genicular nerve block can improve the accuracy of nerve block and reduce block-related complications.This article reviews the research progress of ultrasound-guided genicular nerve block in three aspects:anatomy,operation methods and clinical application.