Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as inter-cellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,im-mune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.

Mitochondria play a crucial role as organelles, managing several physiological processes such as redox balance, cell metabolism, and energy synthesis. Initially, the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria. Recent scholarly works, however, suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer. This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms. Specifically, we review the role of mitochondria transfer in regulating cellular metabolism restoration, excess reactive oxygen species (ROS) generation, proliferation, invasion, metastasis, mitophagy activation, mitochondrial DNA (mtDNA) inheritance, immune system modulation and therapeutic resistance in cancer. Additionally, we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Objective: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC). Methods: Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed. Results: Case 1, carrying germline MLH1 mutation, was diagnosed with Stage IIAm MMRd (International Federation of Gynecology and Obstetrics 2023) endometrial cancer (EC) at 38 years old. She received PD-1 inhibitor treatment and achieved a pathological complete response (CR) at 42 weeks. Case 2, carrying MLH1 mutation, underwent colorectal cancer surgery at 22 years and was diagnosed with EC and synchronous ovarian cancer at 39 years.After 24-week PD-1 treatment, CR of EC and ovarian cancer was achieved. Case 3, carrying MSH2 mutation, was diagnosed with endometrial atypical hyperplasia (EAH) at 35 years.After receiving 7-month progestin, she had the progressed disease with Stage IA2mMMRd EC and colon cancer was found soon after. She received PD-1 treatment for 18 weeks and achieved a CR of EC. She conceived naturally with full term delivery. Case 4, carrying MSH2 mutation, had a recurrence of Stage IBmMMRd EC 15 months after CR from EAH treated with progestin at 40 years. She received PD-1 treatment for 18 weeks and achieved CR. No recurrence was found in all cases after 3–41 months of follow-up after CR. Conclusion ICIs might be an effective choice for LS-EC patients desiring fertility preservation.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

Objective To establish a quantitative analysis of multi-compounds by single-marker(QAMS)method for the simultaneous determination of four compounds in formula granules of Pteris multifida and optimize the extraction process of total flavonoids.Methods The relative correction factors(RCFs)of lonicerin,luteolin and apigenin in the formula granules of Pteris multifida were calculated by using the UPLC method with rhoifolin as the internal reference,and their durability was investigated.The external standard method(ESM)was used to determine the content of four compounds in the formula granules of Pteris multifida,and the difference between the calculated values and the measured values was compared.The effects of ultrasonic time,ethanol volume fraction,solid-liquid ratio and ultrasonic power on the extraction rate of total flavonoids were studied by single factor experiment.On this basis,Box-Behnken test with three factors and three levels was conducted to optimize the extraction process of total flavonoids,and the verification experiment was conducted.Results The content of rhoifolin in the formula granules was 0.035%-0.056%,and the content of lonicerin,luteolin and apigenin by QAMS method was 0.085%-0.167%,0.014%-0.028%and 0.004%-0.008%,respectively,which had no significant difference with the external standard method.The optimal extraction conditions of total flavonoids were 80%ethanol water,solid-liquid ratio 1:20,40 minutes extraction,the average extraction rate was 24.46 mg·g-1.Conclusion The established QAMS method was accurate and feasible,and the optimized extraction process of total flavonoids based on Box-Behnken response surface method was simple and feasible,which could lay a foundation for the quality evaluation of the Pteris multifida formula granules.

Objective:To study the effects of electron beam irradiation and 60Co irradiation on the composition changes of four alkaloids in Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Methods:Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets were irradiated at different doses of 0, 1.5, 3, 5, 7, 10, 20, 30, 40 kGy by electron beam irradiation and 60Co irradiation. The contents of oxymatrine, oxysophocarpine, matrine and sophocarpine were determined by HPLC, and the changes of the components before and after irradiation were compared. Results:Oxymatrine, oxysophocarpine, matrine and sophocarpine were among 0.046 9-0.937 4 μg, 0.020 5-0.410 4 μg, 0.098 9-1.977 9 μg, 0.048 7-0.973 1 μg, respectively. The linear relationship was good. The average recovery rates were 98.1%, 100.1%, 100.5%, 96.6%, respectively, and the RSDs were 1.69%, 2.03%, 3.14% and 1.10%, respectively. Electron beam irradiation and 60Co irradiation had no statistical significance on the changes of oxymatrine, oxysophocarpine, matrine and sophocarpine in Sophora flavescens, but had statistical significance in the contents of intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Conclusion:The established method for the determination of matrine is accurate, reproducible, simple and practical, and can be used for the quality control of Lixieling Tablets. Irradiation has no significant effect on the content of Sophorae Flavescentis Radix, while high dose irradiation has significant effect on the intermediates and finished products of Sophorae Flavescentis Radix, which can provide a basis for quality control and sterilization irradiation of enterprises.

OBJECTIVE To establish the quality standard of Lixieling tablets. METHODS Thin layer chromatography was used to identify Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix in Lixieling tablets. The components of andrographolium and matrine were determined by HPLC. RESULTS The thin layer spots of Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix were clear, with good separation effect and repeatability. The linear relationship between andrographolide, neoandrographolide, 14-deoxygenated andrographolide, dehydrated andrographolide, sophorine, oxymatrine, sophorine and oxysophorine and their respective concentration ranges was good. The RSDs of instrument precision, repeatability, stability and recovery all met the requirements. CONCLUSION The method is simple and reproducible, and can be used for the quality control of Lixieling tablets.