OBJECTIVE: To investigate the clinical efficacy and safety of venetoclax (VEN) in combination with hypomethylating agent (HMA) in the treatment of patients with high-risk myelodysplastic syndromes (MDS). METHODS: A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included. The overall response rate (ORR), modified overall response rate (mORR), overall survival (OS), progression-free survival (PFS), and adverse events of all included patients were evaluated. RESULTS: Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen, 24 cases achieved complete response (CR)/ marrow complete response (mCR), 2 cases achieved partial response (PR), the ORR was 24/30, the median OS was 28.1 months, and the median PFS was 28.1 months. In addition, patients who achieved complete remission / marrow complete remission after treatment had a significantly longer OS than those who did not. Moreover, 12 patients were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). There were grade 3 or higher hematologic adverse events including thrombocytopenia (14 cases), neutropenia (14 cases), febrile neutropenia (10 cases) and anemia (7 cases) as well as gastrointestinal adverse events of any grade, such as vomiting (7 cases), diarrhea (5 cases), and constipation (4 cases). CONCLUSION VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS. This regimen combined with allo-HSCT can improve the prognosis of these patients. Continuous attention to the monitoring and management of adverse events is essential for the patients' safety in this combination therapy.
Humans ; Myelodysplastic Syndromes/drug therapy* ; Sulfonamides/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Female ; Male ; Treatment Outcome ; Middle Aged ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adult

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Aim To investigate the protective effect of carnosine on BV2 cell damage induced by oxygen-glu-cose deprivation/reperfusion(OGD/R)and its role in mediating pyrodeath through the ROS/NLRP3/GSDMD pathway.Methods BV2 cells were randomly divided into the control group(Con),model group(OGD/R),carnosine group(OGD/R+CAR),inhibitor group(OGD/R+MCC950),and carnosine+inhibitor group(OGD/R+CAR+MCC950).The cell survival rate was detected by MTT assay.The release rate of lactate dehydrogenase(LDH)in cell supernatant was detected by microenzyme labeling method.Cell damage was as-sessed using Hoechst 33342/SYTOX Green staining.ROS levels in cells were detected by DCFH-DA.The nucleation level of NF-κB p65 was observed by immu-nofluorescence.The protein expression levels of NLRP3,ASC,cleaved caspase-1,and GSDMD-N were detected by Western blot.The levels of IL-1 β and IL-18 in the supernatant were detected by ELISA.Results Com-pared with Con group,the survival rate of cells in the OGD/R group was significantly reduced,LDH release was significantly raised,cell morphology was damaged,and the positive rate of SYTOX Green was significantly elevated with ROS level in cells.The fluorescence in-tensity of NF-κB p65 in the nucleus increased,and the protein expression levels of NLRP3,ASC,cleaved caspase-1,GSDMD-N increased significantly,and the levels of IL-1 β and IL-18 in the cell superserum in-creased significantly.Compared with the OGD/R group,the survival rate of cells in other groups in-creased significantly,the LDH release rate significantly decreased,and the cell damage was improved to a cer-tain extent.The positive rate of SYTOX Green and ROS production in cells significantly decreased,and the fluorescence intensity of NF-κB p65 in nucleus markedly decreased.The expression levels of related proteins and the levels of IL-1 β and IL-18 in cell super-natant significantly decreased.Conclusion Carnosine can protect BV2 cells from OGD/R-induced damage by inhibiting oxidative stress and NF-κB activation,then inhibiting NLRP3/GSDMD signaling pathway.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hydrazines/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy*

Objective:To investigate the effect of early postoperative enteral nutrition(EN)on postoperative rehabilitation and inflammation after laparoscopic radical gastrectomy for gastric cancer,in order to provide reference for postoperative rehabilitation of such patients.Methods:Patients who received laparoscopic assisted radical gastrectomy in Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2022 were included in the analysis.According to the different ways of postoperative nutritional treatment,patients were divided into the observation group(early postoperative EN group)and the control group(parenteral nutrition group),and indexes such as postoperative rehabilitation,abdominal drainage flow and the level of inflammatory mediators in drainage fluid were compared between the two groups.Results:A total of 81 patients were included,including 41 in the observation group and 40 in the control group.Interval of the first postoperative exhaust(t=3.806;P＜0.001)and resuming diet day(t=5.510;P＜0.001),and length of postoperative hospital stay(t=2.401;P=0.019)in the observation group were shorter than those in the control group.Levels of peripheral blood albumin(t=14.040;P＜0.001)and prealbumin(t=9.832;P＜0.001)of the observation group at postoperative day(POD)5 were significantly higher than those of the control group,but there was no significant difference in hemoglobin level(t=1.477;P=0.144).The level of CRP in peripheral blood of the observation group at POD 5(t=7.758;P＜0.001)and the incidence of postoperative SIRS[(12.2％,5/41)vs(32.5％,13/40),x2=4.830;P=0.028)]were significantly lower than those in the control group.The average drainage volume(t=6.858;P＜0.001),drainage removal time(t=5.016;P＜0.001),and TNF-α level(t=4.993;P＜0.001)and IL-6 level(t=20.640;P＜0.001)in postoperative drainage at POD 5 were significantly lower in the observation group than those in the control group.Conclusion:Early postoperative EN could accelerate the rehabilitation process after laparoscopic radical gastrectomy,improve postoperative nutritional status,and reduce abdominal inflammation.

Objective: By means of network pharmacology, potential targets and molecular pathways of QiZhenYuanDan in the treatment of atherosclerosis (AS) were studied. Methods: TCMSP database was used to obtain the main active components and target information of Astragali Radix, Fructus Ligustri Lucidi, Corydalis Rhizoma and Salvia Miltiorrhiza in QiZhenYuanDan. Disease targets were retrieved by OMIM and other databases. Molecular networks were constructed using Cytoscape. STRING database was searched and PPI network diagram was drawn to obtain the key targets of QiZhenYuanDan in the treatment of AS; and the targets were uploaded to Metascape data platform for GO and KEGG analysis. Results: There were 118 targets of intersection between QiZhenYuanDan and AS, which were used as the predicted targets of QiZhenYuanDan on AS. GO analysis showed that the biological functions of QiZhenYuanDan in the treatment of AS targets mainly involved biological processes, such as the cytokine-mediated signaling pathway, cytokine receptor binding. KEGG pathway was mainly enriched in 155 signaling pathways, including PI3K-Akt, HIF-1, NF-κB signal pathway and inflammatory bowel disease pathway. Conclusion: Based on the result of network pharmacology study, the mechanisms of Qizhenyuandan for AS treatment was preliminarily revealed. The active ingredients such as quercetin and kaempferol act on targets such as IL-6 and PI3K-Akt, and exert anti-AS effects by inhibiting apoptosis, oxidative stress, as well as inflammatory responses. Our result indicates that QiZhenYuanDan exhibits anti-AS effect via a multi-component, multi-target and multi-route synergistic process.
Atherosclerosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.
Adrenocorticotropic Hormone ; China ; Cushing Syndrome/surgery* ; Female ; Gout ; Humans ; Hydrocortisone ; Iatrogenic Disease ; Male ; Skin, Artificial ; Wound Infection