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*

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.

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.

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.

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 analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.

Objective:To construct a cluster care of oral nutrition supplements (ONS) , and to explore its effect in home care of postoperative patients with gastric cancer.Methods:Literature search was conducted to review the status quo of ONS compliance at home in patients with gastric cancer after surgery, and analyze the existing problems. We summarized and formulated the cluster care plan according to the evidence, and established the home ONS management team and process. From November 2020 to October 2021, 107 patients with gastric cancer who needed to implement ONS at home in Gastrointestinal Surgery of Ningbo First Hospital were selected as research objects by convenience sampling. Postoperative patients with gastric cancer from November 2020 to April 2021 were set as the control group ( n=40) , and those from May to October 2021 were set as the observation group ( n=67) . The control group was treated with conventional ONS, and the observation group was treated with home ONS cluster care plan on the basis of the control group. The compliance of nutritional support, weight gain, body mass index increase and follow-up experience between the two groups were evaluated. Results:After six months of intervention, the scores of ONS compliance, weight gain, body mass index increase and follow-up experience in the observation group were significantly higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The cluster care plan improves the ONS compliance at home, nutritional status and satisfaction with the follow-up by medical and nursing staff in patients with gastric cancer after surgery, which is worthy of clinical promotion.

Objective:To explore the nutritional status and quality of life of gastric cancer patients one month after operation in the context of enhanced recovery, and analyze the correlation between them.Methods:From August 2020 to August 2021, 168 patients discharged from the Gastrointestinal Surgery of Ningbo First Hospital after radical resection of gastric cancer were selected as the study subject by convenience sampling. The Nutritional Risking Screening 2002 (NRS2002) and the Global Leadership Initiative on Malnutrition (GLIM) step 2 (excluding muscle mass measurement index) were used to assess the postoperative nutritional status of patients. The quality of life of patients with gastric cancer after operation was investigated with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) . Logistic regression analysis was used to explore the influencing factors of nutritional status of postoperative patients with gastric cancer. A total of 168 questionnaires were distributed, and 168 valid questionnaires were recovered, with a valid recovery rate of 100.0%.Results:A total of 104 patients (61.9%) had nutritional risk and 46 patients (27.4%) had malnutrition. There were statistical differences in age, education level, tumor stage, body mass index, physical function, role function, emotional function, cognitive function, general health, fatigue, nausea and vomiting, and loss of appetite among gastric cancer patients with different nutritional status after operation ( P<0.05) . Logistic regression analysis showed that body mass index, physical function, role function, emotional function and fatigue were the influencing factors of the nutritional status of patients one month after operation ( P<0.05) . Conclusions:In the context of enhanced recovery, the nutritional risk and malnutrition rate of gastric cancer patients one month after operation are high, and are closely related to the quality of life. When implementing enhanced recovery after surgery, medical and nursing staff should strengthen and optimize the nutrition management of gastric cancer patients before hospital, during perioperative period and after discharge, improve the nutritional status after operation and the quality of life of patients.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China