OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells,leading to alterations in the recipient cells,suggesting that EVs play an important role in intercellular communication.EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools.At present,although the mechanisms of exosome biogenesis and secretion in donor cells are well understood,the molecular mechanism of EV recognition and uptake by recipient cells is still unclear.This review summarizes the current understanding of the molecular mechanisms of EVs'biological journey in recipient cells,from recognition to uptake and cargo release.Furthermore,we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo,which is crucial for studies applying EVs as drug-targeted delivery vehicles.Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

OBJECTIVE To prepare patchouli oil enteric-coated dropping pills, evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC). METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters. Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids. Finally, colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1; and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9 ℃, and dropping pills at the speed of 33 drops·min−1, with dropping distance set at 6 cm; the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid. Compared with free patchouli oil, patchouli oil enteric-coated dropping pills significantly alleviated the pathological symptoms such as weight loss, hematochezia and colon shortening in rats; the expression of pro-inflammatory cytokines IL-6, IL-1β, and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated. The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α was significantly down-regulated. CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective:To investigate the current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

Objective:To investigate the current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

Standardization is the universal language of the world, and standardization of traditional Chinese medicine (TCM) is essential for its communication in China and globally. However, the principles and methods of TCM acupuncture standardization have been unclear and inadequate in the early stages. Based on an investigative approach to understanding the current status, identifying problems, and finding solutions, our team has established basic principles of TCM acupuncture that embody Chinese wisdom, evaluated the international strategic environment systematically, proposed the principle of “importance of harmony and exercise of impartiality”, and established basic working principles. A series of methods for TCM acupuncture standard development and evaluation have been constructed, including general standards for the revision of TCM acupuncture standards, the first TCM acupuncture clinical research management specification, a shared full chain technology platform, a data center, and an evaluation research base for TCM acupuncture clinical research. Evaluation criteria for ancient literature and expert experience, a recommendation method for the “three main and three auxiliaries” TCM guideline for prevention were established, and quantifiable assessment methods of TCM standard applicability were proposed. These findings provide methodological guidance for TCM acupuncture standardization.

OBJECTIVE: To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM). METHODS: Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored. RESULTS: The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants. CONCLUSION The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.
Humans ; Immunoglobulin Heavy Chains/genetics* ; Multigene Family ; Mutation ; Waldenstrom Macroglobulinemia/genetics*

Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Lymphoma, Non-Hodgkin/drug therapy* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols