Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

OBJECTIVE: To explore the functional rehabilitation of patients with rheumatoid arthritis (RA) after total knee arthroplasty (TKA). METHODS: A retrospective analysis was conducted on 101 patients who needed TKA due to rheumatoid arthritis (RA) involving both knees from January 2017 to December 2020, including 16 males and 85 females, aged from 41 to 65 years old with an average of (58.13±5.53) years old;body mass index (BMI) ranged from 16.88 to 33.33 kg·m^-2 with an average of (23.16±3.49) kg·m^-2;63 patients with grade 1, 29 patients with grade 2, and 9 patients with grade 3 according to classification of American Society of Anesthesiologists (ASA). According to the latest follow-up results at 12 months after operation, 82 patients returned to work and 19 patients did not return to work. Visual analogue scale(VAS) was used to evaluate the degree of pain relief before operation and 12 months after operation, and work, osteoarthritis and joint replacement questionnaire (WORQ) was used to evaluate knee joint activity status of all patients before and after operation, and the working ability index was used to evaluate working ability of all patients before operation and 12 months after operation. For the 82 patients who returned to work, the labor time stopped before operation and within 12 months after operation was compared, and the changes in labor grades, types of work and labor hours of patients before and after operation were recorded. For the 19 patients who did not return to work, the specific reasons for their non-return to work was analyzed;the postoperative satisfaction of patients was evaluated by using Likert satisfaction scale. All patients were followed up for at least 12 months. VAS was decreased from (6.49±0.59) before operation to (1.10±0.43) at 12 months after operation (P<0.05);for WORQ questionnaire survey, scores of walking, sitting posture, standing and stair climbing were increased from (1.07±0.35), (1.05±0.29), (1.06±0.34) and (1.14±0.42) before operation to (3.00±0.00), (2.87±0.33), (2.95±0.21) and (2.95±0.21) after operation, respectively, had statistically significant (P<0.05);the labor work index of all patients increased from 1.11±0.46 before operation to 2.99±0.10 at 12 months after operation, and the difference was statistically significant (P<0.05). Among the 82 patients who returned to work after operation, regarding the time of stopping labor, 81 patients stopped working within 3 months before operation, 1 patient stopped working for 4 to 6 months after operation, and the number of patients who stopped working was 81, 1, and 0 respectively. Forty patients returned to work within 3 months after operation, 4 to 6 months after operation for 29 patients, and 12 months after operation for 13 patients. 95.1% (78/82) of patients engaged in light labor before operation, and 85.4% (70/82) of patients engaged in moderate labor after operation. At 12 months after operation, the types of jobs and working hours available to all patients increased compared with those before operation. Among 19 patients who did not return to work after TKA, 7 patients had poor control of rheumatoid arthritis, 5 patients still felt pain, swelling and numbness on knee joint, 2 patients had retired, and 5 patients had other reasons. Eighty-six patients (85%) expressed great satisfaction with the postoperative working ability, 8 patients (8%) expressed satisfaction with the postoperative working ability, 6 patients (6%) expressed acceptance of postoperative working ability, and 1 patient (1%) expressed dissatisfaction with postoperative working ability. CONCLUSION TKA is an effective treatment option for patients with RA. After undergoing TKA, patients could significantly improve pain and functional activities of knee joint, and effectively enhance the quality of life and working ability. For patients whose rehabilitation labor capacity is not fully met, postoperative management and personalized rehabilitation treatment need to be strengthened to achieve the best rehabilitation effect.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/rehabilitation* ; Arthritis, Rheumatoid/physiopathology* ; Middle Aged ; Aged ; Retrospective Studies ; Adult

OBJECTIVE: To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL). METHODS: A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment. RESULTS: A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group. CONCLUSION At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans ; Lymphoma, Mantle-Cell/pathology* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; ROC Curve

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents