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.

Objective To perform single-molecule, real-time sequencing of ceftazidime-avibactam (CAZ-AVI)-resistant Pseudomonas aeruginosa and to investigate the mechanism underlying ceftazidime-avibactam resistance in P. aeruginosa. Methods The susceptibility of 89 P. aeruginosa isolates randomly sampled from clinical specimens in Sanming First Hospital Affiliated to Fujian Medical University from November 2021 through July 2023 to common antimicrobial agents was tested, and the minimum inhibitory concentration (MIC) of CAZ-AVI was determined against P. aeruginosa with a broth microdilution assay, with CAZ-AVI MICs of 8 mg/L and lower defined as susceptible and 16 mg/L and higher as resistant. The expression of drug-resistant genes ampC, oxa-488, oprD, mexA, oxa-10, oxa-14, vim and tem was quantified in P. aeruginosa using a real-time quantitative reverse transcription PCR (qPCR) assay. CAZ-AVI-susceptible and -resistant P. aeruginosa isolates from the same case were selected for PacBio single-molecule, real-time sequencing, and sequencing results were subjected to genome structure and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations. Results The 89 P. aeruginosa isolates showed a relatively high level of resistance to meropenem (75.28%) and imipenem (74.16%) and the highest susceptibility to amikacin (91.01%). There were 49 CAZ-AVI-resistant P. aeruginosa isolates and 40 susceptible isolates. qPCR assay detected lower oprD gene expression in CAZ-AVI-resistant P. aeruginosa isolates [0.104 (2.385)] than in susceptible isolates [0.551 (17.885)] (Z = -2.958, P < 0.01), and there were no significant differences between CAZ-AVI-susceptible and -resistant P. aeruginosa isolates in terms of ampC, oxa-488, mexA or tem gene expression (all P values > 0.05), while oxa-10, oxa-14 and vim gene was expressed in few P. aeruginosa isolates. There were 1 729, 3 936, 3 737 and 3 955 genes in CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 and susceptible isolates PA-885 and PA-808 that were annotated to GO terms, with the highest numbers of genes enriched in the molecular function of catalytic activity, high numbers of genes enriched in biological processes of metabolic process, single-organism process and cellular process, and high numbers of genes enriched in cellular components of cell and cell membranes. There were 1 803, 4 084, 3 915 and 4 066 genes in the PA-762, PA-M174, PA-885 and PA-808 isolates enriched in the KEGG signaling pathway, and the majority of genes were enriched in four primary signaling pathways of metabolism, genetic information processing, environmental information processing and cellular process, with the highest number of genes associated with metabolic pathways. Both CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 carried multiple efflux pumps systems, including MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM. Single nucleotide substitution was found at position 169 in the DNA sequence of the PA-762 isolate, leading to substitution of serine for glycine at position 57 in the protein sequence, and there are deletions of two bases at positions 307 and 308 in the DNA sequence of the PA-M174 isolate, leading to substitution of threonine for arginine at position 103 in the protein sequence. Conclusion Mutation or downregulation of oprD gene may lead to CAZ-AVI resistance in P. aeruginosa.

Objective:To analyze the clinical features, prognosis and risk factors of SARS-CoV-2 associated acute pancreatitis (SAAP), and provide a basis for early prevention and treatment of SAAP.Methods:Patients with coronavirus disease 19 infection (COVID-19) admitted to Zhejiang Provincial People's Hospital from December 1, 2022 to January 31, 2023 were retrospectively analyzed. Clinical characteristics such as age, gender and other data were recorded, and the indexes of blood routine, liver and kidney function, inflammatory factor, coagulation function, blood gas analysis, immunoglobulin and complement were collected after admission. Patients were divided into pancreatic injury group and non-pancreatic injury group according to the level of serum amylase/lipase. The difference of prognosis and related hematological parameters between the two groups was compared. Multifactorial logistic regression equation was constructed to analyze the risk factors of SAAP.Results:A total of 2 101 patients with COVID-19 who met the criteria were included, including 298 patients in the pancreatic injury group and 1 803 patients in the non-pancreatic injury group. 17 cases (5.7%) in the pancreatic injury group met the diagnostic criteria for AP. The age, male percentage and mortality rate of the pancreatic injury group were all significantly higher than those of the non-pancreatic injury group (all P<0.05). In the pancreatic injury group, white blood cell count, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), calcitoninogen, erythrocyte sedimentation rate, inflammatory cytokines, tumour necrosis factor, liver and kidney functions, coagulation (D-dimer and plasma fibrinogen degradation products), and lactate level were significantly higher than those in the non-pancreatic injury group (all P<0.05). Serum complement C3, albumin, albumin globule ratio and arterial oxygenation index were lower in the pancreatic injury group (all P<0.05). Multifactorial logistic regression analysis showed that gender, age, CRP, calcitoninogen, total bilirubin, creatinine, PaO 2, PaO 2/FiO 2 and lactate were independent risk factors for the occurrence of pancreatic injury in patients with COVID-19 (all P<0.05). Conclusions:Inflammation-related markers, D-dimer and fibrinogen degradation products were significantly higher in COVID-19 patients comorbid with pancreatic injury than in the patients without pancreatic injury. The risk of SAAP was significantly higher in male patients of senior age. Sex, age, CRP, calcitoninogen, total bilirubin, creatinine, oxygenation index, and lactic acid were independent risk factors for the onset of pancreatic injury in COVID-19 patients.

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

Objective:To analyze the efficacy and safety of flumatinib,a second-generation tyrosine kinase inhibitor(TKI)independently developed in China,in patients with chronic myelogenous leukemia in chronic phase(CML-CP)who falied first-line and second-line treatment.Methods:The clinical data of 30 CML-CP patients treated with flumatinib in Lianyungang First People's Hospital from January 2020 to September 2022 were collected retrospectively.Among them,15 patients who received imatinib first-line treatment but failed treatment were included in the second-line group,and the other 15 patients who failed second-line treatment with nilotinib or dasatinib were included in the third-line group.The hematological and molecular responses of the patients in the two groups at 3,6 and 12 months of treatment,and the event-free survival(EFS)and adverse reactions of patients at the end of follow-up were statistical analyzed.Results:At 3,6,and 12 months of treatment,10,11,and 12 patients in the second line group achieved major molecular response(MMR),which was higher than that of 3,4,and 5 patients in the third line group(P=0.010,P=0.011,P=0.010).At 3 months of treatment,12 and 13 patients achieved complete hematological response(CHR)and early molecular response(EMR)in the second-line group,which was higher than that of 9 and 13 patients in the third-line group,but the difference between the two groups was not statistically significant(P=0.232,P=1.000);At 6 and 12 months of treatment,6 and 7 patients in the second-line group achieved MR4.5,which were higher than of 3 and 2 cases in the third-line group,but the difference was not statistically significant(P=0.427,P=0.713).The hematological adverse reactions of patients in the second-line group during treatment the period were mainly grade 1-2 thrombocytopenia and anemia,and no grade 3-4 of adverse reactions occurred.In the third-line group,there were 2 cases of grade 1-2 thrombocytopenia,grade 1-2 anemia and white blood cell 3 cases were reduced each,1 case of grade 3-4 anemia,2 cases of grade 3-4 neutropenia.The non-hematological adverse reactions in the second-line group were rash(2 cases),headache(1 case),diarrhea(1 case),fatigue(1 case),limb pain(1 case).There were 1 cases of diarrhea,1 cases of nausea,and 1 cases of edema in the third-line group.There was no statistical significance in hematological and non-hematological adverse reactions between the two groups of patients(P＞0.05).At the end of follow-up,the EFS rate of patients in the second-line group was higher than that in the third-line group(100％vs 93.3％),but the difference was not statistically significant(P=0.317).Conclusion:The second-generation TKI flumatinib independently developed in China,has good curative effect and safety for CML-CP patients who failed first-line and second-line treatment.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Objective:To explore the clinical efficacy and safety analysis of a novel laser localization technology assisted percutaneous puncture of trigeminal nerve microsphere capsule compression surgery for the treatment of primary trigeminal neuralgia.Methods:A retrospective selection was conducted on 63 patients with primary trigeminal neuralgia who underwent percutaneous puncture of the trigeminal nerve microsphere capsule compression surgery at the First Hospital of Hunan University of Chinese Medicine from January 2020 to December 2021. According to different surgical methods, they were divided into a new laser localization assisted puncture group (observation group) of 32 cases and a traditional barehanded localization puncture group (control group) of 31 cases. An analysis was conducted on the surgical time, puncture time, puncture frequency, intraoperative exposure to radiation, number of cases of poor balloon formation, and clinical efficacy within 6 months after surgery for two groups of patients. The prognosis of the patients was followed up at 6 months after surgery.Results:The surgical time, puncture time, puncture frequency, and intraoperative exposure of the observation group were all less than those of the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference ( P>0.05) in the number of cases of poor balloon angioplasty between the observation group and the control group, as well as the pain score grading of the Barlow Neurological Institute (BNI) on the first day after surgery. Within 6 months after surgery, there was no statistically significant difference in the incidence of facial numbness, diplopia, masseter weakness, perilabial herpes, and recurrent pain between the two groups of patients (all P>0.05). Conclusions:Laser positioning technology can assist in precise puncture of the foramen ovale and accurate placement of balloons based on surgical experience, which helps to improve surgical safety, reduce postoperative complications and intraoperative radiation dose, and achieve satisfactory short-term follow-up results.