Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of combination regimen containing daratumumab in multiple myeloma (MM) patients. METHODS: The clinical data of 14 newly diagnosed MM patients and 58 relapsed refractory MM patients treated with combination regimen containing daratumumab from November 2020 to March 2023 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. The efficacy and safety of combination regimen were analyzed. RESULTS: The median age of the 72 patients was 62 (38-78) years, including 35 males and 37 females. The overall response rate (ORR) of patients receiving first-line, second-line, and third-line or above treatment was 92.9% (13/14), 68.2% (30/44), and 42.9% (6/14), respectively. The median progression-free survival (PFS) was not reached, 15.4 months, and 9.7 months in three groups, respectively (all P <0.05), while the median overall survival (OS) was all not reached. Among relapsed refractory patients, the ORR of those treated with DVd, DPd and DRd regimen was 50.0% (12/24), 40.0% (4/10) and 100% (10/10), the median PFS was 2.8 months, 10.3 months and not reached, and the median OS was 15.4 months, not reached and not reached, respectively. Furthermore, the PFS and OS in the DRd group were superior to those in the other two groups (all P <0.05). Cox univariate and multivariate analysis showed that lactate dehydrogenase (LDH) ≥250 U/L and extramedullary disease were independent adverse prognostic factors for PFS, and LDH ≥250 U/L was also an independent adverse prognostic factor for OS. Hematologic adverse reactions were mainly lymphopenia (87.5%) and thrombocytopenia (52.8%), while non-hematologic adverse reactions were mainly infusion-related reactions (19.4%) and infections (11.1%). CONCLUSIONS The combination regimens containing daratumumab can be used as first-line treatment for patients with newly diagnosed MM. In patients with relapsed refractory MM, early use of regimens containing daratumumab may improve treatment response rate and prolong PFS. The DRd regimen has better therapeutic response and survival advantages. LDH is an independent prognostic factor affecting PFS and OS in MM patients.
Humans ; Multiple Myeloma/drug therapy* ; Middle Aged ; Aged ; Male ; Female ; Antibodies, Monoclonal/administration & dosage* ; Adult ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective:To evaluate the relationship between superoxide dismutase 2 (SOD2) lactylation and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy-ferroptosis during cerebral ischemia-reperfusion (IR) in mice.Methods:Thirty-six clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=9 each) using a table of random numbers: sham operation group (Sham group), cerebral IR group (IR group), IR+ glycolysis inhibitor 2-DG group (IR+ 2-DG group), and IR+ 2-DG+ NCOA4 overexpression group (IR+ 2-DG+ LvNCOA4 group). The model of cerebral IR injury was established by occlusion of the middle cerebral artery for 1 h followed by 24 h of reperfusion using the intraluminal suture method in anesthetized animals. 2-DG 250 mg/kg was intraperitoneally injected at 90 min before ischemia in IR+ 2-DG and IR+ 2-DG+ LvNCOA4 groups. The lentivirus overexpressing NCOA4 2 μl was injected into the ventricles at 7 days before ischemia in IR+ 2-DG+ LvNCOA4 group. The percentage of cerebral infarct volume was determined, the viable neurons were counted, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were measured by enzyme-linked immunosorbent assay. The expression of SOD2, lysine 114 lactylation of superoxide dismutase 2 (SOD2-K114la), NCOA4, microtubule-associated protein 1 light chain 3β (LC3B), and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined by Western blot. Mitochondrial morphology was examined by electron microscopy. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, the expression of SOD2-K114la, NCOA4, LC3B and ACSL4 was up-regulated, the expression of SOD2 was down-regulated ( P<0.05), and the mitochondrial injury was aggravated in IR group. Compared with IR group, the percentage of cerebral infarct volume was significantly decreased, the number of viable neurons was increased, the mitochondrial injury was alleviated, the levels of ROS and MDA were decreased, the content of GSH was increased, the expression of SOD2-K114la, NCOA4 and ACSL4 was down-regulated, and the expression of SOD2 and LC3B was up-regulated in IR+ 2-DG group ( P<0.05). Compared with IR+ 2-DG group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, and the expression of NCOA4, LC3B and ACSL4 was up-regulated ( P<0.05), no significant change was found in the expression of SOD2 and SOD2-K114la ( P>0.05), and the mitochondrial injury was aggravated in IR+ 2-DG+ LvNCOA4 group. Conclusions:SOD2 lactylation promotes NCOA4-mediated ferritinophagy-ferroptosis by enhancing oxidative stress, thereby contributing to the cerebral IR injury in mice.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.