This study aims to integrate data mining techniques of single cell transcriptomics and spatial transcriptomics, along with animal experiment validation, so as to systematically characterize the protective effects of Jianpi Tongluo Formula(JTF) on the cartilage in knee osteoarthritis(KOA) and elucidate the underlying molecular mechanisms. Single cell transcriptomics and spatial transcriptomics datasets(GSE254844 and GSE255460) of the cartilage tissue obtained from KOA patients were analyzed to map the single cell-spatial heterogeneity and identify key pathogenic factors. After that, a KOA rat model was established via knee joint injection of papain. The intervention effects of JTF on the expression features of these key factors were assessed through real-time quantitative polymerase chain reaction(PCR), Western blot, and immunohistochemical staining. As a result, the integrated single cell and spatial transcriptomics data identified distinct cell subsets with different pathological changes in different regions of the inflamed cartilage tissue in KOA, and their differentiation trajectories were closely related to the inflammatory fibrosis-like pathological changes of chondrocytes. Accordingly, the expression levels of the two key effect targets, namely nuclear receptor coactivator 4(NCOA4) and high mobility group box 1(HMGB1) were significantly reduced in the articular surface and superficial zone of the inflamed joints when JTF effectively alleviated various pathological changes in KOA rats, thus reversing the abnormal chondrocyte autophagy level, relieving the inflammatory responses and fibrosis-like pathological changes, and promoting the repair of chondrocyte function. Collectively, this study revealed the heterogeneous characteristics and dynamic changes of inflamed cartilage tissue in different regions and different cell subsets in KOA patients. It is worth noting that NCOA4 and HMGB1 were crucial in regulating chondrocyte autophagy and inflammatory reaction, while JTF could reverse the regulation of NCOA4 and HMGB1 and correct the abnormal molecular signal axis in the target cells of the inflamed joints. The research can provide a new research idea and scientific basis for developing a personalized therapeutic schedule targeting the spatiotemporal heterogeneity characteristics of KOA.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Osteoarthritis, Knee/pathology* ; Humans ; Male ; Cartilage, Articular/metabolism* ; Chondrocytes/metabolism* ; Rats, Sprague-Dawley ; Female ; Protective Agents/administration & dosage* ; Single-Cell Analysis ; Middle Aged ; HMGB1 Protein/metabolism*

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the application of painless diagnosis and treatment technology in children's peripherally inserted central catheter(PICC)guided by ultrasound.Methods Totally 82 children who planned to undergo PICC in the hospital from January 2021 to January 2023 were selected and randomly divided into a control group and an observation group using a random number table method,with 41 cases in each group;The control group underwent conventional ultrasound guided PICC catheterization,while the observation group underwent painless diagnostic and therapeutic techniques using ultrasound guided PICC catheterization;Compare the success rate of catheterization,completion time of catheterization,degree of pain in the child pain[children's pain behavior scale(FLACC)],tolerance[Houpt behavior scale(HBS)],compliance[Frankl scale(FCS)],and family satisfaction between the two groups.Results The success rate of catheterization in the observation group was higher than that in the control group,and the catheterization time was shorter than that in the control group,with a statistically significant difference(P<0.05).The FLACC score of the observation group was lower than that of the control group,while the HBS score and FCS score were higher than those of the control group,with a statistically significant difference(P<0.05);The total satisfaction of family members in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion The use of painless diagnosis and treatment technology in ultrasound-guided PICC catheterization in children can improve the success rate of catheterization,shorten the catheterization time,reduce the degree of pain in children,enhance tolerance and compliance,and improve family satisfaction.

This study investigates whether compounds in Salvia miltiorrhiza Bunge can bind to the Toll like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) protein complex and exhibit anti-inflammatory activity. Virtual screening of reported chemical components of Salvia miltiorrhiza Bunge against TLR4/MD2 was conducted in this study. The selected compound, neoprzewaquinone A (Neo A), was tested for its impact on the binding of lipopolysaccharide (LPS) to receptors on the cell membrane, its affinity for the protein, its influence on the dimerization of TLR4 and MD2 in LPS-induced cells, and its effects on the phosphorylation of nuclear factor-κB (NF-κB) p65 protein and the secretion of inflammatory cytokines in cells. Results indicate that Neo A in Salvia miltiorrhiza Bunge exhibited the highest virtual binding affinity with TLR4/MD2, with a value of -12.8 kcal·mol^-1. Neo A significantly inhibited the binding of LPS to receptors on the cell membrane (P < 0.01). Moreover, Neo A demonstrated affinity for rhTLR4/MD2, rhTLR4, and rhMD2, with K_D values of 267, 534, and 228 nmol·L^-1, respectively. Amino acid residues like TYR131 and PHE121 in TLR4/MD2 might play a role in the alkyl and π-alkyl hydrophobic interactions with Neo A. Neo A also significantly inhibited the dimerization of TLR4 and MD2 in LPS-mediated cells (P < 0.01) and markedly suppressed the phosphorylation of NF-κBp65 protein (P < 0.05). Furthermore, Neo A significantly or markedly inhibited the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced cells (P < 0.05, P < 0.01). In conclusion, Neo A exerts its anti-inflammatory effects by binding TLR4/MD2 then disrupting the binding of LPS to TLR4/MD2. It may serve as a TLR4/MD2 inhibitor with the potential to treat inflammation-related diseases targeting TLR4/MD2.

This article reports a single case of a patient with systemic lupus erythematosus(SLE)combined with pure red cell aplasia(PRCA),and reviews 51 additional cases of patients reported by domestic and overseas papers from 1974 to 2021.These 52(51+1)cases were analyzed to summarize the epidemiological features,clinical features,laboratory inspections,treatments and prognosis of the patients.The results indicated that among all the 52 cases,cases of SLE combined with PRCA were mostly seen in Asian childbearing age women.The median ages of patients diagnosed with SLE and diagnosed with PRCA were 31.5 years and 36.0 years,respectively.The time interval between the initial diagnosis of SLE and subsequent diagnosis of PRCA was significantly longer than the interval for the initial diagnosis of PRCA,suggesting a delayed onset of SLE in these patients(P=0.042).Various clinical features of the 52 patients were reported,including mostly fatigue,joint pains,Raynaud phenomena and rashes,and SLE maybe combined with autoimmune hemolytic anemia(AIHA),thymoma,hypothyroidism and myasthenia gravis(MG).In these reported cases,laboratory indicators showed higher proportions of antinuclear antibody(ANA),anti double stranded DNA antibody(anti-dsDNA antibody),positive urinary protein and low complement levels.Among the 52 patients,51 cases(98.08%)were treated with glucocorticoids,followed by blood transfusion,cyclosporin A,cyclophosphamide and high-dose intravenous immunoglobulin.Of the 50 patients whose prognoses were reported,44 showed improvement,while 3 treatments were not effective and 3 resulted in death.This article aims to enhance the understanding of SLE combined with PRCA among doctors.

Objective:To investigate the diagnosis of dual-energy X-ray absorptiometry(DXA)for osteoporosis(OP)of postmenopausal patients with rheumatoid arthritis(RA)in Qinghai region and the risk factors of them.Methods:A total of 200 postmenopausal female RA patients who admitted to Qinghai Hospital of Traditional Chinese Medicine from May 2022 to April 2023 were selected.All patients were tested for bone mineral density(BMD)after admission,and lumbar spines L1-L4,whole lumbar,large trochanter,Ward's triangle area,whole body and whole forearm were measured by DXA.According to the results of BMD test,patients whose BMD T values of all body parts-2.5 SD were less or equal to-2.5 were included in the OP group(121 cases),and patients whose BMD T value of all body parts were larger than-2.5 SD were included in the non-OP group(79 cases).The BMD T value of different body parts between two groups of RA patients were compared and analyzed.The area under curve(AUC)of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of BMD T value for OP.The logistic regression method was adopted to analyze the risk factors that postmenopausal RA patients of Qinghai region occurred OP.Results:The BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangular area,whole body and whole forearm of OP group were obviously lower than those of the non-OP group.In analysis of ROC curve,the sensitivities of BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangle area,whole body and forearm were respectively 96.20%,95.22%,90.16%,96.03%,92.01%,89.36%,99.26%,90.02% and 96.03% in diagnosing OP,and the specificities of them were respectively 81.00%,82.19%,85.22%,83.06%,83.06%,90.22%,80.06%,86.23%,83.09%,and the AUC values of them were respectively 0.908,0.905,0.896,0.906,0.903,0.879,0.918,0.901 and 0.906.The results of the logistic-regression analysis showed that advanced age,long disease course,rheumatic activity scores of 28 joints,erythrocyte sedimentation rate and Calcium supplementation were the risk factors of occurring OP in postmenopausal RA patients in Qinghai region.Conclusion:The DXA method that detects BMD of RA patients who occur OP can be used as gold standard to assess OP,and there are many risk factors that affect the occurrence of OP in postmenopausal RA patients of Qinghai region.The clinical work should combine with relative factors to formulate reasonable measure so as to reduce the incidence of OP.

Objective To compare the effect of 8-week high-intensity interval training(HIIT)and moderate-intensity continuous training(MICT)on body composition and cardiovascular risk biomarkers in middle-aged and elderly obese women,so as to provide theoretical and practical basis for future in-tervention.Methods Thirty-four middle-aged and elderly obese women were randomly divided into an HIIT group(n=13),a MICT group(n=12)and a CON group(n=9).All subjects underwent a laboratory VO2max test before intervention to determine their corresponding exercise load.Then,HIIT group rode a power bicycle for 2 minutes at 80%～85%VO2max intensity and 1 minute at 30%VO2max intensity,re-peated 10 times,while MICT group rode at 65%VO2max intensity for 30 minutes,3 times a week for 8 weeks.CON group did exercise.Before and after intervention,all groups were measured their body weight,body fat,muscle mass,body fat rate,as well as the serum levels of high-sensitivity c-reac-tive protein(hs-CRP),endothelin-1(ET-1),lipoprotein(a)[Lp(a)]and homocysteine(Hcy).Results Af-ter intervention,there was a significant decrease in the body fat and body fat rate(P<0.05)and a sig-nificant increase in muscle mass(P<0.05)in the HIIT group,while there were no significant changes in the above three values in the MICT group(P>0.05).Moreover,there was a significant decrease in hs-CRP and ET-1 of the HIIT group(P<0.01),and a significant increase in Hcy and Lp(a)of the CON group(P<0.01).Meanwhile,the decrease in hs-CRP(P<0.05),Lp(a)(P<0.05)and Hcy(P<0.01)of the HIIT group,as well as that in Hcy(P<0.05)of the MICT group were significantly higher than the CON group.What's more,no significant differences were observed between HIIT and MICT groups in their effects(P>0.05).Conclusions HIIT is superior to MICT in improving body composition and reducing serum levels of hs-CRP and ET-1 in middle-aged and elderly obese women.Moreover,it has a positive effect on improving chronic inflammatory state and vascular endothelial function,to a certain extent,and lowering their risk of suffering from cardiovascular diseases.

Aim To investigate the effect of quercetin(Que)on podocyte inflammatory injury and the under-lying mechanism.Methods MPC5 cells were divided into normal glucose group(NG),mannitol group(MA),high glucose group(HG)and high glucose+quercetin group(HG+Que).Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry.The expression of SIRT1,STAT3,apoptosis-related proteins(Bax,Bcl-2,caspase-3)and pyroptosis pro-tein GSDME was detected by Western blot.The ex-pression levels of inflammatory factors(IL-6,TNF-α,IL-18,IL-1β)in cell supernatants were detected by ELISA.Then small interfering RNA technology was used to knockdown SIRT1 expression.To further eval-uate the biological significance of SIRT1 in response to high glucose and Que treatment,negative control group(HG+si-NC+Que)and SIRT1 interference group(HG+si-SIRT1+Que)were added in the presence of high glucose and Que.Results Compared with the high glucose group,40 μmol·L-1 Que could alleviate the apoptosis of MPC5 cells induced by high glucose,decrease the expression of apoptosis related protein Bax and caspase-3,as well as increase the expression of anti-apoptotic protein Bcl-2;ELISA results showed that Que could decrease the expression of TNF-α,IL-6,IL-1 β and IL-18 induced by high glucose.Mechanical-ly,Que could alleviate the inhibitory effect of high glu-cose on the expression of SIRT1,and further decrease the activation of STAT3 and N-GSDME,and inhibit pyroptosis.Compared with the si-NC group,si-SIRT1 group could reverse the protective effect of Que on the high glucose induced inflammatory damage of podo-cytes,the expression of apoptotic proteins Bax and caspase-3 increased,while the expression of anti-apop-totic protein Bcl-2 decreased.At the same time,the levels of inflammatory cytokines TNF-α,IL-6,IL-1 βand IL-18 in supernatants increased,and the expres-sion of STAT3 and N-GSDME increased.Conclusion Que could inhibit pyroptosis and relieve the inflam-matory damage of podocytes through SIRT1/STAT3/GSDME pathway.

To address the challenge of unclear features and difficulties in pulmonary nodule CT image detection,an efficient attention feature pyramid network is proposed.The network firstly employs a feature pyramid of multi-scale feature fusion as the backbone network for effectively preserving both low-and high-level features,and uses the depthwise separable convolutional neural network to extract feature information.Then,the attention mechanism is integrated into the backbone network for assigning weights to salient feature information.Finally,the proposed algorithm is applied to Lung-PET-CT-Dx dataset and Luna16 dataset,and the experimental results demonstrate that the proposed algorithm has higher precision,recall rate and mAP value than the existing comparative algorithms,substantiating its superiority in pulmonary nodule detection.