ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

Objective To investigate the relationship between perioperative nutritional risk and venous thromboembolism(VTE)in patients with hip fracture.Methods A total of 379 patients with unilateral hip fracture due to fall or sprain who underwent elective surgery were selected and divided into the non-VTE group(246 cases)and the VTE group(133 cases)according to whether or not VTE occurred during perioperative period.Basic information,surgical and anesthesia records,nutritional risk related indicators,inflammatory indicators and outcome indicators of patients were collected.Multiple Logistic regression was used to analyze the independent influencing factors of perioperative VTE.Receiver operating characteristics(ROC)curves were used to assess the ability to discriminate independent factors,and DeLong test was used to compare area under the curve(AUC).Results Compared with the non-VTE group,the proportion of patients in the VTE group was older,complicated with hypertension,the time to visit hospital more than 2 days,received(hollow/intramedullary nail)internal fixation,perioperative blood transfusion,ASA gradeⅢtoⅣ,and higher nutritional risk screening Table(NRS)-2002 scores on admission and higher postoperative neutrophil/lymphocyte ratio(NLR).Nutritional prognosis index(PNI),hemoglobin(Hb)and prealbumin(PA)at admission and after operation were lower in the VTE group than those in the non-VTE group(P＜0.01).Multivariate Logistic regression analysis showed that PNI was decreased,NRS-2002 scores and PA were increased,and the time of visit hospital was>2 days after internal fixation.American College of Anesthesiologists(ASA)gradesⅢ-Ⅳwere independent risk factors for perioperative VTE of hip fracture(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of NRS-2002 at admission was 0.739(0.692-0.783),and that of PNI at admission was 0.720(0.672-0.765),both of which were better than other influencing factors(P＜0.01).Conclusion NRS-2002 and PNI are good predictors of perioperative VTE in patients with hip fracture.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

The conventional acupoint therapy for rheumatoid arthritis often uses traditional Chinese medicine preparations in the dosage forms of powder, ointment, and paste. However, these dosage forms have obvious drawbacks, such as low transdermal absorption, strong skin irritation, and easy detachment. Creating a traditional Chinese medicine acupoint therapy characterized by high penetration, low toxicity, low irritation, and convenient administration is of great significance. With the development of new technology for modern traditional Chinese medicine preparations, modern dosage forms such as microemulsion, microparticle, hydrogel, and liposome are combined with acupoint administration, and the derived therapeutic methods include acupoint application, acupoint injection, microneedle, and nanoporous acupuncture needle. The combination of new dosage forms of traditional Chinese medicine preparations and acupoint administration has the advantages of high drug permeability, high retention, and the formation of drug acupoint storage. The accumulation of drugs in acupoints continuously amplifies the acupoint effect, achieving a synergistic effect of drug treatment and acupoint treatment(1+1>2). This article reviews the relevant research and improvement of new dosage forms of traditional Chinese medicine preparations combined with acupoint administration for the treatment of RA, providing new development ideas for the combination of traditional Chinese medicine acupoint therapy and modern new formulation technologies.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Acupuncture Points ; Dosage Forms ; Medicine, Chinese Traditional/methods* ; Animals

Objective:To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD + acute myeloid leukemia (AML) with normal karyotype. Methods:The clinical data of FLT3-ITD + AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results:The study included 49 patients with FLT3-ITD +AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD + ( P>0.05) . There were 12 patients with high-frequency FLT3-ITD + in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion:Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD + patients, particularly those with FLT3-ITD high-frequency mutation.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

BCR-ABL^T315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABL^T315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.
Humans ; Drug Resistance, Neoplasm/genetics* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Fusion Proteins, bcr-abl/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Mutation ; Antineoplastic Agents/pharmacology*

ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg^-1） and Niaoduqing Granules group （2.6 g·kg^-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Animals ; Coronary Vessels ; Diabetes Mellitus ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Rats