Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective To analyze the epidemiological characteristics of hand-foot-mouth disease(HFMD)in Gan-zhou.Methods The epidemiological data of HFMD reported by the Infectious Disease Surveillance System,a sub-system of China Disease Prevention and Control Information System,from 2017 to 2020 were analyzed by descriptive methods.Enterovirus(EV)nucleic acid and typing detections via throat swabs,anal swabs or herpes fluid of patients was detected by real-time fluo-rescent polymerase chain reaction.The change in HFMD epidemic characteristics was compared between 2020 and 2017-2019.Results The incidence of HFMD in Ganzhou in 2020 was significantly lower than that from 2017 to 2019(x2=50.587,P＜0.05).In 2020,the incidence of HFMD in counties and districts of Ganzhou(except Huichang County)signifi-cantly decreased compared with that in 2017-2019(P＜0.05).From 2017 to 2019,the incidence of HFMD was obviously seasonal,with a high incidence in summer and autumn,and two significant incidence peaks were formed in June and September in 2017 and 2018,respectively.In 2019,there was a summer peak in June.The epidemic trend in 2020 was different,with a very low epidemic trend in summer and autumn,and a peak in winter.The incidence of HFMD in men,women and all ages in 2020 significantly decreased compared with that in 2017-2019(P＜0.05),and the age of onset was mainly distributed in 1-5 years,especially in children aged 1 to 3 years.There was a significant difference in the incidence of HFMD among different ages(P＜0.05).The positive rate of EV in Ganzhou in 2020 was lower than that from 2017 to 2019(x2=47.273,P＜0.05).The positive rate of EV in January,March to September in 2020 was significantly lower,and the positive rate of EV in November,December 2020 was significantly higher than that in the same period in 2017 to 2019(P＜0.05).Strain CA16 showed an increasing trend year by year from 2017 to 2019,and became the dominant strain in 2019.The proportion of patients infected with CA6 strain was on the fise from 2018 to 2020,and CA6 became the dominant strain in 2020.Conclusion The HFMD in Ganzhou has obvious population characteristics and seasonality,and the pathogen spectrum is constantly changing.

Objective:To establish a graded method to avoid mean fluorescence intensity(MFI)threshold of HLA Class I antibodies corresponding antigen,and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes.Evaluate the application value of combining both methods in selecting HLA compatible platelets(PTL)for patients with immune platelet transfusion failure(IPTR)in improving platelet the corrected count increment(CCI).Methods:A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence(SPRCA)method for 51 IPTR patients.The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients,and detected the MFI value for different specificity antigens of HLA Class I antibodies,was graded into strong positive group(MFI＞4 000,level 1),medium positive group(1 000＜MFI 4 000,2),weak positive group(500＜MFI≤1 000,3),and one negative control group(MFI≤500).The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups,the statistical differences between the four groups were compared.Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases,and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients.The donor with the minimum number of epitopes mismatches was selected,while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2,the provision of HLA compatible platelets for IPTR.After the transfusions,the CCI value of the platelet transfusion efficacy evaluation index was calculated,and the clinical evaluation of the transfusion effect was obtained through statistical analysis.Results:There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group,medium positive group,and weak positive group of 51 IPTR patients with different specific of HLA-I class antibodies and corresponding antigens(all P＜0.001).The positive results showed a range from high to low,with strong positive group＞medium positive group＞weak positive group.There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P＜0.001).There was no statistical difference between the weakly positive group and the negative control group(P＞0.05).The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold,the medium positive group as the grade 2 avoidance thresholds,and the weak positive group as the grade 3 avoidance threshold.In the case of donor platelet shortage,it is not necessary to avoid the weak positive group.Avoiding the strategy of donor antigens and HLAMatchmaker program scores≤7 corresponding to HLA Class I antibodies of levels 1 and 2,with CCI values＞4.5 × 109/L within 24 hours,can obtain effective clinical platelet transfusion conclusions.Conclusion:When selecting HLA Class I compatible donors for IPTR patients,the grading avoids HLA Class I antibodies corresponding to donor antigens,and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected.The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

Patient 1,a 12-day-old female infant,presented with fever,cough,dyspnea,and elevated infection markers,requiring respiratory support.Metagenomic next-generation sequencing(mNGS)of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila(LP),leading to diagnoses of LP pneumonia and LP sepsis.The patient was treated with erythromycin for 15 days and azithromycin for 5 days,resulting in recovery and discharge.Patient 2,an 11-day-old female infant,presented with dyspnea,fever,elevated infection markers,and multiple organ dysfunction,requiring mechanical ventilation.mNGS of blood and cerebrospinal fluid indicated LP,leading to diagnoses of LP pneumonia,LP sepsis,and LP intracranial infection.The patient was treated with erythromycin for 19 days and was discharged after recovery.Neonatal LP pneumonia lacks specific clinical symptoms,and azithromycin is the preferred antimicrobial agent.The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.

To explore the feasibility and experience of kidney transplantation with horseshoe kidney as donor kidney. The horseshoe kidney donated by a brain dead donor was obtained by in-situ perfusion and whole piece incision. After methylene blue staining was injected into the inferior pole artery of the kidney and separated from the isthmus along the edge of the stained site, two kidney donors were divided into two recipients with successful implantation. After renal transplantation, the blood supply of the two donor kidneys was good. During the perioperative period, there was no bleeding or urine leakage. Postoperative ureteral obstruction occurred in one recipient. After the double J-tube drainage was ineffective, autologous ureter was anastomoted with the renal pelvis of the transplanted kidney. Up to now, the renal function of two recipients remained stable. According to literature analysis, kidney transplantation with well-functioning horseshoe kidney as donor kidney is safe and feasible, but its postoperative complication rate is higher than that of conventional kidney transplantation.

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

Aim To study the anti-inflammatory activ¬ity of diterpenes from Tripterygium wilfordii on lipopo- lysaccharide ( LPS)-induced macrophage and its mech¬anism. Methods MTT assay was used to detect the cytotoxicity of compounds. The Griess method was used to detect the NO on LPS-induced RAW264. 7 cells. ELISA was applied to determine the contents of inter- leukin 6 (IL-6) , tumor necrosis factor a ( TNF-a ) , interleukin lp (IL-lfj) and interleukin 18 (IL-18) in cell culture supernatant. Western blot was used to de¬tect IkBcx, .INK, ERK, p38, STAT3 and their phos-phorylation in LPS-induced RAW264.7, as well as the effect on COX-2, iNOS, NLRP3, caspase-1 , cleaved- caspase-1. Flow cytometry was employed to detect the effects of compounds on the phagocytosis of RAW 264. 7 cells. Results Hypoglicin II (1) and ent-pimara-8 (14) , 15-diene-19-ol (6) , two diterpenoid compounds from Tripterygium wilfordii could effectively inhibit the expression of inflammatory mediators ( COX-2 and iN- OS) and inflammatory cytokines (IL-6, IL-lp, IL- 18) in LPS-induced RAW264. 7 cells. Further re¬search found that the phosphorylation of IkBcx , JNK, ERK, P38, STAT3 and NLRP3 was all inhibited; however, there was no significant effect on the expres¬sion of IkBcx, JNK, ERK, P38 and STAT3. At the same time, they also inhibited the phagocytosis of mac-rophages. Conclusions The anti-inflammatory mecha¬nism of Tripterygium wilfordii diterpenoids 1 and 6 might be through inhibiting the production of NLRP3 inflammatory bodies, inflammatory mediators (COX-2 and iNOS) and inflammatory cytokines (IL-6, IL-lp and IL-18) , which is closely related to inhibiting the activation of MAPK, NF-kB and STAT3 pathway.

OBJECTIVE: To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals. METHODS: A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality. RESULTS: Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81). CONCLUSION In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Humans ; ST Elevation Myocardial Infarction/therapy* ; Percutaneous Coronary Intervention ; East Asian People ; Treatment Outcome ; Myocardial Reperfusion ; Myocardial Infarction ; Registries ; Hospitals

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.
Humans ; Influenza, Human ; Sentinel Surveillance ; Syndrome ; China ; Cell Phone