OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To explore the incidence and risk factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries and its correlation with preoperative risk assessment of cerebrovascular events,so as to guide perioperative risk management.Methods A retrospective study was conducted on 40 patients aged≥18 years who underwent non-cardiac and non-neurosurgical surgeries and experienced perioperative ischemic stroke in the First Affiliated Hospital of Henan University of Science and Technology from January 2015 to January 2022,forming the stroke group.A control group of 160 patients without perioperative ischemic stroke was selected in a 1:4 case-control ratio,matched for gender,age,date of operation,and the surgeon.Clinical data and preoperative risk assessment of cerebrovascular events(including the single or combined application of head CT/MRI,transcranial Doppler ultrasound,carotid ultrasound,and neurological consultation)of the two groups of patients were collected and statistically analyzed.Multiple logistic regression analysis was used to identify risk factors associated with perioperative ischemic stroke.Results The incidence of perioperative ischemic stroke was 0.042%.Multiple logistic analysis results showed that hypertension(OR=7.858,95%CI 2.175-28.388,P=0.002),hyperlipidemia(OR=4.457,95%CI 1.320-15.049,P=0.016),renal insufficiency(OR=8.277,95%CI 1.480-46.282,P=0.016),and intraoperative hypotension(OR=3.862,95%CI 1.211-12.317,P=0.022)were independent risk factors for perioperative ischemic stroke in non-cardiac and non-neurological surgeries;preoperative cerebrovascular risk assessment(OR=0.130,95%CI 0.031-0.542,P=0.005)was a protective factor against it.Conclusions The incidence of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgery is low but has a poor prognosis.Hypertension,hyperlipidemia,renal insufficiency,and postoperative hypotension are risk factors for perioperative ischemic stroke,while preoperative cerebrovascular event risk assessment is beneficial to reducing its incidence.

Analyze the changes in phenolic components and gene expression profiles of Tetrastigma hemsleyanum leaves with supplemental blue light, and screen differentially expressed genes related to phenolic metabolism, providing a basis for improving the quality of T. hemsleyanum leaves. Using the leaves of T. hemsleyanum under supplemental blue light and visible light as research materials, the content of phenolic components such as neochlorogenic acid, chlorogenic acid, and 3-O-coumaroyl quinic acid was significantly increased by supplemental blue light. A total of 102 949 unigenes were obtained from the transcriptome, including 14 564 differentially expressed unigenes. They can be divided into 52 subclasses by gene ontology (GO) function, kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis showed that these differentially expressed unigenes were significantly enriched in phenolic metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis and isoflavone biosynthesis. A total of 63 differentially expressed unigenes were identified in the pathways related to the biosynthesis of phenolic cpmponents, including 19 key enzymes such as phenylalanine ammonia-lyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), flavonol synthase (FLS), and so on. This study greatly enriched the genetic data information of T. hemsleyanum and laid a foundation for analyzing the mechanism of blue light promoting the biosynthesis of phenols and molecular breeding of T. hemsleyanum.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

As a major global public health problem, pulmonary diseases threaten human life and health while causing a huge economic burden. The messenger RNA (mRNA)-based inhalation preparation, which effectively targets pulmonary cells can overcome the problems of traditional therapy, such as high side effects, low pulmonary bioavailability, and difficulty in synthesizing target proteins in vitro, thus providing new ideas for the treatment of pulmonary diseases. However, as the lung structure is complex and mRNA has trouble entering cells, researchers have been attempting to develop a suitable nano delivery system for higher delivery efficiency. This review introduces the barriers to pulmonary delivery, discusses the recent research development of the mRNA pulmonary delivery systems, including lipid nanoparticles, polymeric nanoparticles, polypeptides and exosomes, summarizes their limitations and looks forward to the application of mRNA inhalation preparations.

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell