A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

Objective To explore the effect of Dong's extraordinary point acupuncture combined with medium frequency pulse electrotherapy on lumbar disc herniation.Methods Eighty patients with lumbar disc herniation who were admitted to Xiangshan Hospital of Traditional Chinese Medicine from January 2021 to October 2023 were selected and randomly divided into study group and control group,with 40 cases in each group.Twelve patients were lost during treatment,and eventually 68 patients were enrolled in this study,including 34 in the study group and 34 in the control group.The control group was treated with conventional acupuncture combined with medium frequency pulse electrotherapy,and the study group was treated with Dong's extraordinary point acupuncture with medium frequency pulse electrotherapy,both for 2 weeks,3 times a week.Visual Analogue Scale(VAS)score,Japanese Orthopaedic Society(JOA)score and Oswestry Disability Index(ODI)were compared between the two groups before and after treatment.Results VAS score and ODI were significantly decreased and JOA score was significantly increased after treatment in both groups(P<0.001).VAS score and ODI in the study group were lower than those in the control group after treatment,while JOA score in the study group was higher than that in the control group(P<0.001).Conclusion Dong's extraordinary point acupuncture combined with medium frequency pulse electrotherapy is superior to conventional acupuncture combined with medium frequency pulse electrotherapy in treatment of lumbar disc herniation.It can faster relieve clinical symptoms and restore lumbar disc function,and is worthy of clinical application with satisfactory safety.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Objective:To evaluate the efficacy and safety of radiofrequency introduction of L-vitamin C in patients with melasma.Methods:From March to June 2019, 20 patients with melasma were admitted to the Department of Dermatology, the Seventh Medical Center of PLA General Hospital, including 19 females and 1 male, aged 30-60 years, with an average age of 43.5 years. All patients were treated with 22 percent of L-vitamin C once a week, a total of 8 times of treatment and followed up for 12 weeks. Each subject was assessed with standardized clinical photo, skin tests (VISIA skin image analyzer and CK multifunctional skin tester) and patient self-assessment. In addition, the adverse reactions were recorded.Results:Physician evaluation and patient self-evaluation showed that skin symptoms were improved obviously after treatment. 90% of the subjects thought that all of the skin moisture, pores, fine lines, glossiness, and color spots were improved after 12 weeks. The skin texture, ultraviolet stain and the brown spots which were detected with VISIA skin image analyzer were all improved after one week and one month. Difference was statistically significant ( P<0.05). Skin glossiness was significantly improved, skin moisture content increased and melanin decreased, which were detected with CK multifunctional skin tester. The differences were statistically significant ( P<0.05). But there was no significant change in transdermal water loss and red pigment index ( P>0.05). Conclusions:22% L-vitamin C can be used to treat melasma and improve photoaging safely without affecting skin barrier function.

Objective:To explore the risk factors for myelosuppression in elderly lung cancer patients undergoing chemotherapy and construct a risk prediction model for myelosuppression in elderly lung cancer patients undergoing chemotherapy.Methods:Using the convenient sampling method, data of 228 elderly patients with lung cancer undergoing chemotherapy in Respiratory Department of a Class Ⅲ Grade A hospital in Zhenjiang from May 2018 to May 2019 were selected, and risk factors of adverse reactions of myelosuppression in patients were analyzed statistically. The binomial Logistic regression was applied to construct the prediction model and the area under the ROC curve was used to test the prediction effect of the model. The patient data from January to May 2020 were collected to validate the model.Results:Among the 228 patients, 75 patients developed myelosuppression, with an incidence of 32.89%. Multivariate analysis results showed that platinum-containing chemotherapy regimens, combined with other adverse reactions, decreased albumin before chemotherapy and decreased hemoglobin before chemotherapy were independent risk factors for myelosuppression in elderly lung cancer patients during chemotherapy ( P<0.05) , which were included in the model. The area under the ROC curve of the final model was 0.823, the maximum Youden index was 0.5, sensitivity was 81.3%, and specificity was 70.5%. The results of the verification data showed that the area under the ROC curve was 0.846, sensitivity was 90.4% and specificity was 68.2%. Conclusions:The prediction effect of this model is good, which can provide reference basis for clinical treatment and formulating nursing measures to prevent myelosuppression.

Objective To study miRNA expression differences in ovalbumin(OVA)- induced murine asthma models of mice and mast cells stimulated by inflammatory cytokines stimulation,and to better understand asthma deve-lopment so as to provide potential target for its prevention and treatment. Methods OVA - induced murine asthma models were validated by detecting cells in bronchoalveolar lavage fluid(BALF)and histopathology. And miRNA ex-pression differences in the lung tissues between the model group and the normal control group were detected by real -time polymerose chain reaction PCR . After tumor necrosis factor - α(TNF - α),interleukin 12(IL - 12)stimulation, miRNA expression differences in murine mast cells P815 were detected. Results The number of total cells and eosino-phil cells both increased in BALF of the model group[(12. 8 ± 2. 2)x 107 / L vs(5. 6 ± 2. 5)x 107 / L,t = 4. 760,P ﹤0. 05;(6. 6 ± 1. 9)x 107 / L vs(0. 8 ± 0. 8)x 107 / L,t = 8. 068,P ﹤ 0. 05]. In addition,histopathology showed more inflammatory cell infiltration in the model group than that in the normal control group,indicating that the models were validated. The expression of miRNA - 155 was up - regulated approximately 5. 0 - fold in the lung tissues of the model group(P ﹤ 0. 05),while miRNA - 192 showed no differences compared with the controls. After TNF - α and IL - 12 stimulated P815 mast cells,miRNA - 192 expressions in P815 were expression in P815 was up - regulated approximate-ly 1. 9 - fold and 1. 7 - fold after TNF - α and IL - 12 stimulation,respectively(P ﹤ 0. 05). Conclusions It is conclu-ded that miRNAs are differentially expressed in the presence of OVA - induced murint asthma models and mast cells stimulated by inflammatory cytokines. These differentially expressed miRNAs may regulate the function of mast cells and involved in the pathogenesis of asthma.