Objective:To investigate the efficacy of azacitidine combined with CAG regimen in the treatment of acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy.Methods:A retrospective case-series study was conducted. A total of 67 AML patients with newly diagnosed elderly, treatment-related secondary and myelodysplastic syndromes or myeloproliterative neoplasms primary transformation who were not suitable for intensive chemotherapy were selected from Heze Municipal Hospital from January 2020 to December 2023. Azacitidine combined with CAG regimen was given for treatment, and the efficacy and adverse reactions of the patients were observed.Results:Among the 67 patients, there were 32 females and 35 males with the median age [ M ( Q1, Q3)] of 68 (65, 72) years old. There were 40 cases in the high-risk group, 13 cases in the medium-risk group, and 14 cases in the low-risk group. After 1 course of treatment with azacitidine combined with CAG regimen, the overall response rate (ORR) was 38.8% (26/67), with a complete remission (CR) rate of 20.9% (14/67), a complete remission rate with incomplete recovery of blood cell count (CRi) of 11.9% (8/67), and a partial remission (PR) rate of 6.0% (4/67). After 4 courses of treatment, the ORR was 59.7% (40/67), with a CR rate of 56.7% (38/67) and a CRi rate of 3.0% (2/67). There were no PR patients. All patients in the low-risk and medium risk groups achieved at least CRi, while the ORR in the high-risk group was 40.0% (16/40). There was a statistically significant difference in efficacy between different risk groups ( P < 0.001). The patient had mild adverse reactions, mainly pain and grade 1-2 hematological adverse reactions. Conclusions:AML patients who are intolerant to intensive chometherapy are effectively treated with azacitidine combined with CAG regimen, and the adverse reactions are mild.

Objective To determine the optimal extraction process for kaempferol from Alpinia officinarum Hance and to investigate its antioxidant activity.Methods Based on single-factor experimental data,this study employed the Box-Behnken central composite design and response surface methodology(RSM),combined with high-performance liquid chromatography(HPLC),to plot response surface and contour maps using kaempferol content as the response value.The optimal parameters for ethanol concentration,solid-liquid ratio,extraction time,and extraction temperature were selected.The antioxidant activity of kaempferol was comprehensively evaluated by calculating the radical scavenging rate using the DPPH radical scavenging assays.Results The optimal extraction conditions were determined to be an ethanol concentration of 84%,a solid-liquid ratio of 1∶80,an extraction time of 2 hours,and an extraction temperature of 82℃.Under these conditions,the kaempferol content extracted from Alpinia officinarum Hance reached 0.034 16%.In the DPPH radical scavenging assay,the extract showed a scavenging rate of 91.20%at a concentration of 1 mg/mL.Conclusion The optimized extraction process for kaempferol from Alpinia officinarum Hance was obtained using the Box-Behnken response surface design method,and this process is practical and feasible.The DPPH radical scavenging assay demonstrated that kaempferol from Alpinia officinarum Hance possesses antioxidant activity.

OBJECTIVE To analyze the types and control measures of major microorganisms in pharmaceutical water systems, so as to provide guidance for effective control of pharmaceutical water systems. METHODS The main microbial species, abundance and harmfulness of drinking water, purified water and water for injection were reviewed, and the control measures on microorganisms in pharmaceutical water were discussed. RESULTS There were differences in the main microbial types in pharmaceutical water. Burkholderia cepacia complex and Ralstonia pickettii were conditioned pathogens in pharmaceutical water, thus causing certain biological safety hazards. CONCLUSION Pharmaceutical companies can strengthen the control of microorganisms in the water system by establishing microbial databases and common microbial strain banks at all levels. Trend analysis should to be conducted based on alert limits and action limits, so as to strengthen the control of microorganisms in the water system.

Objective: To explore the trend of blood pressure among children and adolescents and its correlation with pubertal development and nutritional status, so as to provide a scientific basis for developing prevention strategies targeting early stage hypertension. Methods: In September 2023, a multi stage random cluster sampling was used to select 20 241 primary and secondary school students aged 7-18 years from 57 schools in Jinzhong, whose height, weight, and blood pressure were measured. The Chi square test for trend was used to analyze the change trend in the detection rate of elevated blood pressure and hypertension in children and adolescents with the development of adolescence puberty, and the Logistic regression was used to analyze the correlation between elevated blood pressure and hypertension and nutritional status. Results: The prevalence of elevated blood pressure was 17.3% among children and adolescents. The middle and late pubertal groups had the highest prevalence (23.2% and 24.3%), followed by the early pubertal group (19.5%) and the prepuberty group (10.8%) ( χ 2 trend =372.86， P <0.01). The prevalence of hypertension was 14.8%, with the highest prevalence reported in the late pubertal group (22.4%), followed by the middle pubertal group (18.9%), and the early pubertal (13.0%)/prepuberty (12.2%) groups ( χ 2 trend =175.43， P <0.01). The prevalence of elevated blood pressure and hypertension increased with pubertal development, regardless of gender, region, or nutritional status ( χ 2 trend =9.21-771.90, P <0.01). Overweight and obesity were influencing factors of elevated blood pressure and hypertension among children and adolescents during all stages of pubertal development ( OR =1.2-2.8， P <0.01). Conclusion The prevalence of elevated blood pressure and hypertension among children and adolescents during pubertal development is high, showing an increasing trend with pubertal development.

  Objective   To systematically assess the applicability of the clinical practice guidelines (CPGs) integrating Chinese and western medicine, thereby providing reference for enhancing their future usability.   Methods   PubMed, Web of Science, Embase, SinoMed, WanFang Data, and CNKI databases were searched for guidelines for the integration of Chinese and western medicine. Supplementary searches of Chinese Medical Association, Chinese Medicine Administration, MedSci websites, Website of China Association of Chinese Medicine, Medlive, Website of Dangdang, Chinese Association of Integrative Medicine and World Federation of Traditional Chinese Medicine Societies were conducted. The search time frame was from inception of the databases to December 31, 2022. Four reviewers independently evaluated the implementability of clinical practice guidelines by using "Clinical Practice Guideline (CPG) implementation evaluation tool".   Results   A total of 61 integrative Chinese and western medicine guidelines were included. Of the guidelines assessed, 9 guidelines(14.75%) exhibited strong implementability, 40(65.57%) demonstrated average implementability, and 12 (19.67%) demonstrated poor implementability. Among the 5 domains, the dimensions of "accessibility" and "implementability" were found to be of high quality, while those of "communication", "ease of identification" and "applicability" were relatively poor. Notably, compared to guidelines published between 2006—2016, those published between 2017—2022 showed improvements in the areas of "identification" and "application".   Conclusions   The implementabilityof the existing clinical practice guidelines of the integrative Chinese and western medicine is average and needs to be improved. In the future, emphasis should be placed on the integration of medical education and research, publicity of the guidelines, continuous medical education and training, a more concise form of recommendations, application of the guidelines by clinicians, and the implementability of the integrative Chinese and western medicine guideline.

Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Glycosidases are widely used in food and pharmaceutical industries due to its ability to hydrolyze the glycosidic bonds of various sugar-containing compounds including glycosides, oligosaccharides and polysaccharides to generate derivatives with important physiological and pharmacological activity. While glycosidases often need to be used under high temperature to improve reaction efficiency and reduce contamination, most glycosidases are mesophilic enzymes with low activity under industrial production conditions. It is therefore critical to improve the thermo-stability of glycosidases. This review summarizes the recent advances achieved in engineering the thermo-stability of glycosidases using strategies such as directed evolution, rational design and semi-rational design. We also compared the pros and cons of various techniques and discussed the future prospects in this area.
Glycoside Hydrolases/genetics* ; Oligosaccharides ; Polysaccharides ; Protein Engineering

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.