Mechanisms of liver injuries caused by traditional Chinese medicines

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Clinical observation of Guipi Decoction Combined with non steroidal drugs on sleep in elderly patients with acute traumatic pain and Qi deficiency constitutionabortion

Objective:To explore the effect of Guipi Decoction Combined with non steroidal anti-inflammatory drugs on sleep time of elderly patients with traumatic pain and Qi deficiency constitution during hospitalization.Methods:A total of 52 elderly patients hospitalized in the orthopedic(trauma)ward of the Second Affiliated Hospital of Zhejiang Chinese Medical University from November 2020 to may 2021 were randomly divided into control group and treatment group.Patients in the control group were treated with loxoprofen sodium tablets immediately after admission,and placebo was added to loxoprofen sodium tablets from the second day of admission;The patients in the treatment group were treated with loxoprofen sodium tablets after admission.Guipi Decoction was added on the basis of loxoprofen sodium tablets from the second day of admission.Before and after admission,all patients used the TCM constitution classification judgment table to evaluate the score of qi deficiency and VAS;From the first day to the fourth day after admission,the bracelet was worn to monitor the sleep time(total sleep time,deep sleep time,light sleep time and awakening times)every night.The patients were scored by VAS after taking drugs every morning.Results:Finally 25 patients in the control group and 24 patients in the treatment group completed the experiment.There was no significant difference in gender,age,fracture location,chronic medical history VAS score and TCM Qi deficiency constitution score,between two groups at admission(P>0.05).At the time of discharge,the score of qi deficiency constitution in the treatment group was 33.724±12.634;The TCM Qi deficiency constitution score of the control group was 42.25±15.912,and there was significant difference between the two groups(P<0.05);and there was significant difference in VAS score between the two groups at discharge(P<0.05).There were significant differences in total sleep time,light sleep time,deep sleep time and night awakening times between the two groups on the second,third and fourth day of admission(P<0.05).Conclusion:1.Guipi Decoction can significantly improve the sleep time of patients with Qi deficiency acute traumatic pain.2.Guipi Decoction can not only improve the constitution of patients with Qi deficiency bias,but also improve the VAS score at discharge.

Complete response of a locally advanced pulmonary hepatoid adenocarcinoma patient to perioperative XELOX-containing chemoimmunotherapy

With morphological features resembling hepatocellular carcinoma,hepatoid adenocarcinoma of the lung(HAL)is a rare and aggressive subtype of lung cancer with a 5-year survival of only 8%.1 Most HAL patients present increased serum alpha-fetoprotein(AFP)levels that are commonly related to poor prognosis.Most insights into HAL have come from case series or reports,and TP53 is frequently mutated in HAL.The heterogeneity of HAL complicates the diagnosis.With no established standard,the management of HAL is modeled on that of classical lung adenocarcinoma,although with dismal outcomes.2 Herein,we reported the effective management of a stage IIIb HAL patient with perioperative chemoimmunotherapy and curative-intent surgery.The patient remained disease-free and minimal residual disease(MRD)-negative for more than one year after surgery.

Uretero-lumbar artery fistula: A case report

BACKGROUND Uretero-arterial fistula(UAF)is a disease that usually involves the aorta,common iliac artery,external iliac artery,hypogastric artery,and lumbar artery.Among them,uretero-lumbar artery fistula(ULAF)is the most unusual type.So,both in China and around the world,the diagnosis and treatment of ULAF is a big challenge.CASE SUMMARY A 55-year-old female patient with a history of pelvic radiotherapy developed unexplained massive hemorrhage during replacement of the right Resonance metallic ureteral double-J tubes due to a long-standing indwelling ureteral stent for ureteral stricture.Later,we found contrast extravasation from the patient's right L4 artery into the ureter under digital subtraction angiography(DSA)and administered polyvinyl alcohol particle embolic agent and coil embolization;hematuria was controlled.Follow-up investigations at 18 mo showed no sign of recurrence.CONCLUSION DSA is very important in the diagnosis and treatment of UAF,and DSA should be preferred when UAF is suspected.In addition,the use of softer ureteral stents in patients with primary disease and risk factors for UAF should be considered to avoid increasing the risk of the development of the disease;endovascular treatment should be preferred in patients who have developed UAF.

Paratesticular liposarcoma: Two case reports

BACKGROUND Paratesticular liposarcoma accounts for approximately 7%of scrotal tumors.They are rare lesions of the reproductive system with approximately 90%of the lesions originating from the spermatic cord.Surgery,with the goal of complete resection,is the mainstay for treatment of this disease.However,treatment consisting of extended resection to decrease local recurrence remains controversial.CASE SUMMARY We report the cases of two patients with paratesticular liposarcomas who were treated with radical testicular tumor resection without adjuvant therapy.Followup investigations at 9 mo showed no sign of recurrence.CONCLUSION Surgery is the first-line treatment,regardless of whether it is a recurrent or primary tumor.Extended resection carries a higher risk of complications and should not be performed routinely.Preoperative radiotherapy can reduce the local recurrence rate without affecting the overall survival.

Green tea and its active compounds in cancer prevention and treatment

Green tea is now widely considered as anticancer substance or food in global.Catechin,the main anticancer component in green tea,exhites the strong biological activity which not only eliminate free radicals showing antioxygenic function,but also suppress cell proliferation as well as induce cancer cell apoptosis via blocking corresponding signaling pathway.Furthermore,several studies have demonstrated it could regulate the gut microbiota.It also could regulate gut microbiota.Through these functions,it plays important roles in the occurrence and development of cancer.Here,the anticancer compounds in green tea,the theoretical basis of TCM,the clinic applications,as well as the anticancer mechanism are reviewed.

Research progress on the relationship between exercise and tumor

Tumor is a major threat of the health of Chinese people at present.Exercise has a certain relationship with tumor and is one of the hot topics in the research of tumor.In this paper,it made a review of the researches on the occurrence and development of tumor,therapeutic effect and prognosis,rehabilitation of tumor patients,and the effect of tumor on exercise in recent years.It indicates that the interaction between exercise and tumor is one of the best prevention methods for tumor and has a positive impact on the prognosis and rehabilitation of tumor patients.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Effect of thermophilic bacterium HB27 manganese superoxide dismutase in a rat model of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)

We investigated the therapeutic effects of superoxide dismutase(SOD)from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)and its underlying mechanisms.A Sprague–Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic(Tt)-SOD intragastrically for 4 weeks.Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining,and Masson staining.Alanine transaminase(ALT),aspartate transaminase(AST),serum creatinine(CR),and blood urea nitrogen(BUN)levels were assayed for all animals.Enzyme-linked immunosorbent assays(ELISA)were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde,nitric oxide,SOD,catalase,and glutathione peroxidase.Reactive oxygen species levels were detected using dichlorofluorescein diacetate.The messenger ribonucleic acid(mRNA)expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction(RT-PCR),and infiltrating inflammatory cells were examined using immunohistochemistry.Nuclear factor-κB(NF-κB)P65,P38,and inhibitor of nuclear factor-κBα(I-κBα)protein levels were determined using western blot.Tt-SOD significantly improved histopathological changes in CP/CPPS,reduced inflammatory cell infiltration and fibrosis,increased pain threshold,and reduced the prostate index.Tt-SOD treatment showed no significant effect on ALT,AST,CR,or BUN levels.Furthermore,Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity.This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3(CD3),cluster of differentiation 45(CD45),and macrophage inflammatory protein 1α(MIP1α)cells.Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBαprotein levels.These findings support Tt-SOD as a potential drug for CP/CPPS.