Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Evaluation of the Strategy and Efficacy of Treatment of Chronic Viral Hepatitis C with the Sofosbuvir/Daclatasvir Combination in a Resource-Limited Country

Introduction: The treatment of viral hepatitis C (HCV), a major public health problem, has evolved considerably since the introduction of direct-acting anti-virals (DAAs). The aim of this study was to evaluate the strategy for initiating treatment with Sofosbuvir/Daclatasvir, and also to assess its efficacy. Patients and Methods: Included were patients aged at least 15 years, with detectable hepatitis C viremia and treated with a pan-genotypic Sofosbuvir/Daclatasvir regimen at the Centre “Hospitalier Universitaire la Référence Nationale de N’Djamena” between October 2019 and October 2023. The APRI score was used to assess fibrosis. Cure was defined by an undetectable viral load 12 weeks after the end of treatment. Results: A total of 835 patients were included (sex ratio 1.55, mean age 50.5 ± 13.73, extremes 20 and 84 years). The 60 - 69 age group was the most represented. The mean APRI score was 0.42 ± 0.29, with extremes of 0.019 and 1.84. The mean viral load was 2,316,193.086 IU/mL. All subjects had good renal function. Cytolysis was absent in 70% of cases. Without genotyping, a pan-genotypic regimen was used in all patients: Sofosbuvir (400 mg)/Daclatasvir (60 mg). The cure rate was 99.4%, with good tolerability. However, four cases of failure were recorded out of the 668 patients who underwent follow-up HCV-PCR testing after 12 weeks of treatment. Conclusion: The Sofosbuvir/Daclatasvir regimen is highly effective, with an excellent safety profile. However, the still high cost of these molecules limits their accessibility to a large proportion of patients.

Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Chronic social defeat stress‑induced depression reduces BCG efficacy by promoting regulatory T‑cell levels in mice

Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.

Assessment of albendazole efficacy against Ascaris lumbricoides at three sites of Andhra Pradesh,Odisha,and Kerala in India

Objective:To assess efficacy of albendazole against Ascaris(A.)lumbricoides among school-children at three sites of Rajahmundry,Sundergarh and Wayanad.Methods:Sites were selected based on soil-transmitted helminths prevalence,different sociocultural-geographical characteristics and operational feasibility.9-12 Years old children from 14 schools were included.The study was conducted in two rounds:baseline&follow up survey.All eligible children found positive for A.lumbricoides at baseline were administered supervised single tablet albendazole 400 mg under the National Deworming Day Initiative.During post-treatment follow-up survey,eligible children who provided second stool sample were included in the final analysis.Stool samples were examined using WHO recommended Kato-Katz technique.Efficacy was estimated based on cure rate(CR)and Fecal Egg Count Reduction Rate(FECRR)among children found positive in baseline and follow-up surveys.Results:328 Out of 625(52.5%)were found positive for A.lumbricoides in the baseline survey and 85 out of 178 samples(47.8%)during post-treatment follow-up survey.Overall,the estimated CR was 52.2%.FECRR(95%CI)for albendazole was 72.6%(79.2%-66.0%).The FECRR was highest in East Godaveri[89.7%(96.8%-82.6%)],followed by Sundergarh[86.4%(95.3%-77.5%)]and Wayanad[69%(81.7%-56.4%)].Conclusions:Our study confirmed overall reduction in FEC although with varying albendazole efficacy for A.lumbricoides infection at three different locations in India.However,these finding may be assessed in context of ongoing MDA under Filaria control program and further studies by in vivo as well as in vitro methods are required to reach to a conclusion on possible resistance if any.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-,2-,and 3-year survival rates of the research group(94.00%,84.00%,and 72.00%,respectively)were significantly greater than those of the control group(80.00%,64.00%,and 40.00%,respectively;P<0.05).Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade,history of hepatitis,number of tumors,tumor size,use of sorafenib,stage of liver cancer,histological differentiation,history of splenectomy and other basic data(P<0.05).Logistic regression analysis demonstrated that high Child-Pugh grade,tumor size(6–10 cm),history of hepatitis,no use of sorafenib,liver cancer stage IIIC,and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension(P<0.05).CONCLUSION Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates.The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade,tumor size(6-10 cm),history of hepatitis,lack of sorafenib use,liver cancer at stage IIIC,and prior splenectomy.

Efficacy and Safety of Micropulse Trans-Scleral Cyclophotocoagulation in Cambodian Patients with Glaucoma

Objective: To evaluate the treatment outcomes of micropulse cyclophotocoagulation in Cambodian glaucoma patients. Materials and Methods: 14 patients were enrolled in this retrospective study that was conducted with the consent over a 14-month period. The medical records were analyzed for variables such as intra-ocular pressure, the number of anti-glaucoma drugs used, visual acuity, pain level, and complications during and after treatment. The main outcome was whether or not there was success or failure, with success being defined as a pressure level between 6 and 21 mmHg and a 30% decrease in IOP by week 24 (with/without drugs). Results: In our study, the mean age of patients was 52.36 ± 9.98 years old (42 to 75 years old). The mean intra-ocular pressure before treatment was 41.00 ± 12.26 mmHg, which decreased to 21.60 ± 8.11 mmHg (41.56% reduction) and 16.94 ± 5.46 mmHg (56.04% reduction) in the 12th and 24th weeks (p p Conclusion: Micro-pulse trans-scleral cyclophotocoagulation is a safe and effective method for lowering pressure in any stage of disease without the use of invasive surgeries.

Comparison of efficacy and safety of nab-paclitaxel and oxaliplatin+S-1 and standard S-1 and oxaliplatin chemotherapy regimens for treatment of gastric cancer

BACKGROUND Gastric cancer(GC)is a relatively frequent clinical phenomenon,referring to ma-lignant tumors emerging in the gastric mucosal epithelial cells.It has a high mor-bidity and mortality rate,posing a significant threat to the health of patients.Hence,how to diagnose and treat GC has become a heated topic in this research field.AIM To discuss the effectiveness and safety of nab-paclitaxel in combination with oxaliplatin and S-1(P-SOX)for the treatment of GC,and to analyze the factors that may influence its outcomes.METHODS A total of 219 eligible patients with advanced GC,who were treated at Qinghai University Affiliated Hospital Gastrointestinal Oncology between January 2018 and March 2020,were included in the study.Among them,149 patients received SOX regimen and 70 patients received S-1 regimen.All patients underwent both preoperative and postoperative chemotherapy consisting of 2-4 cycles each,totaling 6-8 cycles,along with parallel D2 radical surgical treatment.The patients were followed up for a period of three years or until reaching the event endpoint.RESULTS The short-term and long-term efficacy of the P-SOX group was significantly higher than that of the SOX group,and the safety was manageable.Cox multivariate analysis revealed that progression-free survival was associated with perioperative chemotherapy efficacy,tumor diameter≤2cm,high differentiation,and early cTNM(T stands for invasion depth;N stands for node metastasis;M stands for distant invasion)stage.CONCLUSION In comparison to the SOX regimen,the P-SOX regimen demonstrates improved short-term and long-term efficacy with tolerable adverse reactions.It is anticipated that the P-SOX regimen will emerge as a first-line chemotherapy option for GC.Patients with GC who receive effective perioperative chemotherapy(Response Evaluation Criteria in Solid Tumors 1.1,Tumor Regression Grade),have a tumor diameter≤2cm,exhibit high degree of differentiation,and are at an early cTNM stage show better prognosis.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer

BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.

Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer:A meta-analysis

BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.

Efficacy of 1% Permethrin and 2% Permethrin Combined with 1% Piperonyl Butoxide against Rhipicephalus sanguineus Ticks in Naturally Infested Dogs

The aim of the present study was to compare the ixodicide efficacy of 1% permethrin applied as a shampoo-bath in single treatment and a combined formulation of 2% permethrin + 1% piperonyl butoxide applied as powder in a single treatment against Rhipicephalus sanguineus ticks, in naturally infested dogs. Eighteen adult cross-mixed dogs, harboring to at least 20 ticks/animal, were selected on pre-treatment live tick counts. On day 0, the dogs were then divided in 3 groups of 6 animals each, for treatment: Group 1 (G1) received 1% permethrin applied as shampoo-bath (approximately 10 ml/kg bw), according to label instructions. G2 was treated with 2% permethrin + 1% piperonyl butoxide applied as powder, and rubbed as massage on the body, as recommended by the producer. G3 served as a non-treated control. After the treatment, the dogs were checked out for live ticks counting on days 0, 1, 7, and 14. The ixodicide efficacy was assessed based on the percentage reductions of ticks on the days analyzed post-treatment, with respect to the untreated control. Results showed that permethrin alone removed ticks on 81%, 93.1% and 89.6% for days 1, 7 and 14, respectively. The combined formulation of 2% permethrin + 1% piperonyl butoxide exerted a better efficacy of 98.8, 97.7 and 97.0%, respectively. It is concluded that this combined formulation was highly effective at rapidly repelling and killing Riphicephalus sanguineus ticks on naturally infected dogs, showing a significant effect on days 1, 7 and 14 after tick exposure. The sustained high and quick level of efficacy of this combination may well interfere with the transmission of Riphicephalus sanguineus ticks. It is concluded that the sustained high level of efficacy of the permethrin + piperonyl butoxide combination may well exert an additive effect and could interfere with the transmission of Riphicephalus sanguineus ticks.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer:A network meta-analysis of randomized clinical trials

BACKGROUND Gastric cancer(GC)is the fifth most commonly diagnosed malignancy worldwide,with over 1 million new cases per year,and the third leading cause of cancer-related death.AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC.METHODS A comprehensive literature search was conducted,focusing on phase II/III randomized controlled trials(RCTs)assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC.The R0 resection rate,overall survival(OS),disease-free survival(DFS),and incidence of grade 3 or higher nonsurgical severe adverse events(SAEs)associated with various perioperative regimens were analyzed.A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.RESULTS Thirty RCTs involving 8346 patients were included in this study.Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone,and the former had the highest probability of being the most effective option in this context.Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS.Owing to limited data,no definitive ranking could be determined for DFS.Considering nonsurgical SAEs,FLO has emerged as the safest treatment regimen.CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC.Further studies are required to validate these findings.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function

BACKGROUND Hepatectomy is the first choice for treating liver cancer.However,inflammatory factors,released in response to pain stimulation,may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies.AIM To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.METHODS Clinical data from patients with liver cancer admitted to Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed.Thirty-five patients underwent laparoscopic hepatectomy for liver cancer(liver cancer resection group)and 35 patients underwent medical image-guided microwave ablation(liver cancer ablation group).The short-term efficacy,complications,liver function,and immune function indices before and after treatment were compared between the two groups.RESULTS One month after treatment,19 patients experienced complete remission(CR),8 patients experienced partial remission(PR),6 patients experienced stable disease(SD),and 2 patients experienced disease progression(PD)in the liver cancer resection group.In the liver cancer ablation group,21 patients experienced CR,9 patients experienced PR,3 patients experienced SD,and 2 patients experienced PD.No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups(P>0.05).After treatment,total bilirubin(41.24±7.35 vs 49.18±8.64μmol/L,P<0.001),alanine aminotransferase(30.85±6.23 vs 42.32±7.56 U/L,P<0.001),CD4+(43.95±5.72 vs 35.27±5.56,P<0.001),CD8+(20.38±3.91 vs 22.75±4.62,P<0.001),and CD4+/CD8+(2.16±0.39 vs 1.55±0.32,P<0.001)were significantly different between the liver cancer ablation and liver cancer resection groups.CONCLUSION The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar,but liver function recovers quickly after microwave ablation,and microwave ablation may enhance immune function.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma

BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Skin care efficacy study of recombinant humanized collagen based on in vitro level

Studying the skin care efficacy of recombinant humanized collagen based on in vitro level.The stability of the recombinant humanized collagen was first analyzed by treating at different temperatures,then its skincare efficacy based on in vitro level was evaluated by detecting the inhibition rate of elastase,the inhibition rate of collagenase,the protein content of type I collagen in human fibroblasts,the inhibition of reactive oxygen species(ROS)with human keratinocytes,and the effects of the recombinant humanized collagen on the expression of hyaluronic acid(HA),filaggrin(FLG)and transglutaminase 1(TGM1)in keratinocytes.The results showed that recombinant humanized collagen was able to maintain stability at temperatures below 70℃.With regard to its skincare efficacy,recombinant humanized collagen could inhibit elastase and collagenase activities and promote the increase of type I collagen content in human fibroblasts.It also showed good inhibition of ROS in keratinocytes in vitro and could increase the expression of HA,FLG,and TGM1 in keratinocytes.In short,the recombinant humanized collagen exhibited a favourable skin care effect in vitro level.This study proved that it has potential firming,anti-wrinkle,moisturizing,and repairing efficacy,and is a valuable cosmetic raw material.

Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer:A multicenter,open-label,single-arm phase II trial

Background:Currently,the need for new therapeutic strategies involving programmed cell death protein-1(PD-1)monoclonal antibodies in the second-line setting of small cell lung cancer(SCLC)is urgent.This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.Methods:This study included the patients from Cohort 4 of a single-arm,open-label,multicenter,phase II clinical trial.A safety run-in phase was performed under anlotinib(10/12 mg quaque die[QD],days 1–14)plus penpulimab(200 mg intravenously[IV],day 1)in a 21-day cycle,followed by the formal trial in which the patients received anlotinib(12 mg QD,days 1–14)plus penpulimab(200 mg IV,day 1)in a 21-day cycle.The primary endpoint of the safety run-in phase was safety.The primary endpoint of the formal trial phase was the objective response rate(ORR).Results:From April 28,2020,to November 24,2020,21 patients were enrolled from 11 hospitals,including 2 in the safety run-in phase and 19 in the formal trial phase.In the formal trial phase,the ORR was 42.1%(8/19;95%confidence interval[CI]:17.7–66.6%).The median progression-free survival was 4.8 months(95%CI:2.9–11.3 months),and the median overall survival was 13.0 months(95%CI:4.6–not applicable[NA]months).The incidence of grade 3 treatment-related adverse events(TRAEs)was 52.4%(11/21),and the incidence of treatment-related serious adverse events(AEs)was 28.6%(6/21).Two AE-related deaths occurred.The most common AEs were hypertension(57.1%,12/21),hypothyroidism(42.9%,9/21),and hypertriglyceridemia(38.1%,8/21).Conclusions:In patients with SCLC who progressed after first-line platinum-based chemotherapy,the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile,which warrants further investigation.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.