Update of latest data for combined therapy for esophageal cancer using radiotherapy and immunotherapy:A focus on efficacy,safety,and biomarkers

Esophageal cancer usually has a poor prognosis.Given the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune checkpoint inhibitors(ICIs)may have a synergistic effect and good outcome in esophageal cancer.Clinical studies of immunoradiotherapy(iRT)for esophageal cancer have proliferated enormously from 2021 to the present.However,a summary of the efficacy and toxicity of combined therapy to guide esophageal cancer treatment in clinical practice is lacking.For this review,we integrate the latest data to analyze and assess the efficacy and safety of iRT for esophageal cancer.In addition,we discuss better predictive biomarkers,therapeutic options for specific populations,and other challenges to identify directions for future research design.

Combined therapy with bevacizumab and photodynamic therapy for myopic choroidal neovascularization: A oneyear follow-up controlled study

AIMTo evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.

Evaluation of modified hemodilution combined therapy in the treatment of acute ischemic stroke in the elderly

BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method. DESIGN： 1：1 paired grouping according to gender and controlled observation SETTING： Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University. PARTICIPANTS： Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items. According to 1：1 paired principle in gender, 90 enrolled patients were assigned into treated group （n=45） and control group （n=45）. There were 39 male and 6 female in the treatment group, and they were aged （76±6）years, ranging from 71 to 84 years, and hospitalized at the 14^th to 76^th hours after onset. There were 39 male and 6 female in the control group, and they were aged （76±6）years , ranging from 70 to 82 years, and hospitalized at the 16^th to 72^th hours after onset. METHODS： Therapeutic method： Patients of treated group received modified hemodilution combined therapy. 200 mL whole blood of patients was exchanged with 500 mL dextran-40 （including 20 mL danshen parenteral solution and 32 mg heparin） at the beginning of therapy; From the 2^nd day, compound huangqi tea bag （Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid） was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6^th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton（Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ） and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index： Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference （1995） was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5^th, 7^th and 14^th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time. MAIN OUTCOME MEASURES ： ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug. RESULTS： Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate： prothrombin time （PT）, activated partial thromboplastin time （APTT） and thrombin time （TT） of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group： （18.4±1.9）, （41.8±2.1）, （19.7±1.7） s, Before therapy in treated group： （13.4±1.3）, （35.8±1.3）, （12.5±0.9） s, After therapy in control group： （16.9±1.5）, （39.1±1.1）, （11.9±2.1） s, P〈 0.05]：Concentration of fibrinogen （Fbg） after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group： （3.4±0.4） g/L; Before therapy in treated group： （4.3±0.7） g/L; After therapy in control group：（4.0±0.6） g/L; P 〈 0.05]. Platelet aggregation rate decreased from （37.92 ±0.85）% before therapy to （26.42±1.01）% after therapy （P 〈 0.01）. ②Change of blood lipid level： Levels of total cholesterol （TC）, triacylglycerol（TG） and low density lipoprotein cholesterol （LDL-C） of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group： （5.2±0.9）, （1.9±0.9）, （2.08±1.1） mmol/L, before therapy in treated group： （5.9±1.2）, （2.8±0.9）, （3.94±0.5） mmol/L, After therapy in control group： （6.0±1.1）, （2.6±0.8）, （3.84±0.9） mmol/L, P 〈 0.05]. ③Change of hemorheology index： Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy： （43.84±4.55）% ;After therapy： （40.48±4.02）%;P 〈 0.05]. Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [（90±1.2）, （97±2.1） cm/s,P〈 0.01]. ⑤NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group （93%,78%, P 〈 0.05）. ⑥There was no obvious adverse effect. CONCLUSION： Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit, increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.

Treatment of Cervical Spondylopathy with a Combined Therapy

ＴｒｅａｔｍｅｎｔｏｆＣｅｒｖｉｃａｌＳｐｏｎｄｙｌｏｐａｔｈｙｗｉｔｈａＣｏｍｂｉｎｅｄＴｈｅｒａｐｙ￥ＹａｎｇＳｈｕｓｈｅｎｇ（ＴｈｅＨｅａｌｔｈＳｔａｔｉｏｎｏｆＸｉｎｇｔａｉＢｒａｎｃｈｏｆｈｅｂｅｉＣｏｌｌｅｇｅｏｆＦｉｎａｎｃｅａｎｄＥｃ...

Innovative combined therapy for multiple keloidal dermatofibromas of the chest wall: A novel case report

Dermatofibromas are benign soft tissue tumors that predominantly affect the limbs, and more rarely the chest.Keloidal dermatofibroma is a rare subtype with distinct clinicopathological features and an aggressive clinical course. By researching the evolution of the disease in this study, we aimed to summarize our experience of managing a rare patient who underwent five surgeries for keloidal dermatofibroma that developed sequentially in the upper arm and chest and propose a novel treatment for keloidal dermatofibroma. We concluded that keloidal dermatofibroma involving larger areas, high tension sites, and multiple localizations can be treated using the principles of pathological scar management.

Effective combined therapy for pulmonary epithelioid hemangioendothelioma: A case report

BACKGROUND Pulmonary epithelioid hemangioendothelioma(P-EHE)is a rare disease.Thus far,consensus on a standard treatment for P-EHE has not been established given its low incidence worldwide.Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide has been used as an effective combination treatment for human malignancies.However,the efficacy of this combination has not been reported in P-EHE cases.CASE SUMMARY We present the case of a 64-year-old woman with chest tightness,cough,and chest pain.Computed tomography showed multiple unresectable pulmonary nodules.She had been misdiagnosed with lung carcinoma and underwent gefitinib treatment at a hospital.Subsequently,the patient underwent a cardiothoracic surgery for further disease investigation.CD31,CD34,and Vimentin expression were detected in the resected nodule specimens by immunohistochemical analyses,and pathological analyses confirmed the diagnosis of P-EHE.Following this,four cycles of apatinib combined with chemotherapy with doxorubicin/cyclophosphamide were initiated.The patient demonstrated stabilization of multiple bilateral nodules and showed a dramatic improvement in the clinical presentation after combination treatment.The patient could not tolerate the side effects of chemotherapy.Therefore,she then continued apatinib monotherapy,which is ongoing to date.The patient was stable at the last follow-up after 24 mo.CONCLUSION Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide may be an effective therapeutic option for P-EHE treatment.

Photothermal and Chemotherapy Combined Therapy of B-CuS-DOX Based on/pH Dual Stimulation

Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.

Chemotactic nanomotor for multimodal combined therapy of glioblastoma

Glioblastoma(GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier(BBB) and the unique immunosuppressive mechanism, it is hard to achieve significant effects of GBM treatment. Here, a kind of chemotactic nanomotor that loaded with glucose oxidase(GOx) and carboxylated cisplatin(Pt(IV)) prodrug on the L-arginine-derived polymer is proposed. The nanomotors are driven by catalysis of glucose decomposition and the positive chemotaxis towards the GBM microenvironment where inducible nitric oxide synthase and reactive oxygen species are highly expressed. This facilitates the BBB crossing and GBM targeting of the nanomotors. In addition, the released nitric oxide(NO) during propulsion as well as the loaded GOx and Pt(IV) can exert combined NO/starvation/chemotherapy. Meanwhile, it is able to induce and enhance the immune response through multiple pathways, thus better coping with the complexities of GBM treatment.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

A Clinical Study to Assess the Effectiveness of Oral Combination Kit Therapy in Syndromic Management of Abnormal Vaginal Discharge (FEMINE Study) in Kinshasa, Democratic Republic of Congo

Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS® combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS® combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.

Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia:a prospective study

Background The primary objectives of the treatment for the lower urinary tract symptoms （LUTS） associated with benign prostatic hyperplasia （BPH） are to produce rapid, sustained, and safe improvements in the symptoms that affect the quality of life in the majority of men over 50. In this study, we evaluated the efficacy and safety of the combined therapy with terazosin （α1-adrenergic receptor antagonist） and tolterodine （anticholinergic agent） for LUTS associated with BPH. Methods This combination study included 69 patients diagnosed with LUTS associated with BPH based on the International Prostate Symptom Scores （IPSS）, urinary flow rate, prostate volume, urinary residual, and their serum prostate-specific antigen levels. Initially, 191 patients were treated with terazosin 2 mg once daily for one week. Those patients with continued LUTS after the initial treatment were allocated randomly into two groups： terazosin group （n=-36） in which patients were treated with terazosin 2 mg once daily for six weeks, and combination group （n=33） in which patients were treated with both terazosin 2 mg once daily and tolterodine 2 mg twice daily for 6 weeks. Results The IPSS were significantly improved in both groups after treatment, and the reduction of IPSS in the combination group was significantly greater than that in the terazosin group （P〈0.01）. A decrease in urgency, frequency and nocturia were the main contributory factors causing the reduction of IPSS in the combination group. The differences about the peak urinary flow rate and the residual urine from the baseline values were noted in both groups after treatment but were not significant between the two groups. The incidence of adverse effects in the combination group was higher than that in the terazosin group. As expected the most common adverse effect was mouth dryness which was associated with anticholinergic drugs such as tolterodine. Conclusions Patients with LUTS associated BPH appear the improved IPSS after combined therapy with terazosin and tolterodine. This study, although short term and limited numbers of patients, provides evidence that the combined therapy with terazosin plus tolterodine is a good approach for meeting the objectives of rapid, sustained, and safe improvements in the LUTS associated with BPH. And the profile of patients in this study might be used as the indication of such combined therapy for LUTS associated with BPH without urodynamic evaluation.

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis

Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug in multiple sclerosis （MS） therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. Methods Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2＇,3＇-cyclic nucleotide 3＇- phosphodiesterase （CNP）/myelin basic protein （MBP）/the precursor form of nerve growth factor （proNGF）/p75/inducible nitric oxide synthase （iNOS） proteins in cerebral cortex of EAE were detected by Western blotting. Results The combined treatment group had a lower clinical score （0.61±0.06） and demyelinating score （1.33±0.33） than the groups with normal saline （clinical score： 1.39±0.08, P 〈0.001; demyelinating score： 2.75±0.49, P 〈0.05） or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP （1.14±0.06 vs. 0.65±0.04, P 〈0.001）, MBP （1.28±0.14 vs. 0.44±0.17, P 〈0.001）, and decreased expressions of proNGF （1.08±0.10 vs. 2.32±0.12, P 〈0.001）, p75 （1.13±0.13 vs. 2.33±0.17, P 〈0.001）, and iNOS （1.05±0.31 vs. 2.17±0.13, P 〈0.001） proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP （1.28±0.14 vs. 1.01±0.15, P 〈0.05） expression and downregulate iNOS （1.05±0.31 vs. 1.35±0.14, P 〈0.05） expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment （1.08±0.10） than that in UTI （1.51±0.24, P 〈0.05） or methylprednisolone （1.31±0.04, P 〈0.05） treatment group. Conclusion Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.

Application of ablative therapy for intrahepatic recurrent hepatocellular carcinoma following hepatectomy

The post-hepatectomy recurrence rate of hepatocellular carcinoma(HCC)is persistently high,affecting the prognosis of patients.An effective therapeutic option is crucial for achieving long-term survival in patients with postoperative recurrences.Local ablative therapy has been established as a treatment option for resectable and unresectable HCCs,and it is also a feasible approach for recurrent HCC(RHCC)due to less trauma,shorter operation times,fewer complications,and faster recovery.This review focused on ablation techniques,description of potential candidates,and therapeutic and prognostic implications of ablation for guiding its application in treating intrahepatic RHCC.

COMBINED THERAPY OF CAPTOPRIL AND SPIRONOLACTONE FOR REFRACTORY CONGESTIVE HEART FAILURE

It is traditionally considered that angiotensin-converting enzyme inhibitor(ACEI) and spironolactone could not be used simultaneously because of the assumed risk of hyperkalemia.

A combined treatment for patients with dry eye and associated laryngopharyngeal reflux:a real-life approach

AIM:To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome(DES)and associated laryngopharyngeal reflux(LPR).METHODS:The study was retrospective,open,observational,and conducted in a real-life setting.Patients had pathological symptom assessment in dry eye(SANDE)and reflux symptom index(RSI)at baseline.Patients were re-assessed after 1mo and at the end of treatment.The treatment consisted of a three-month course based on the combined therapy:Gastroftal eye drops,one drop three times a day,and Gastroftal tablets,two tablets after lunch and two tablets after dinner.Tear break-up-time(TBUT)test,Schirmer test,RSI,and SANDE questionnaire were evaluated.RESULTS:The study included 253 patients.The mean age was 58±11.19y.TBUT test score and Schirmer’s test significantly increased(both P<0.001)after 1mo and at the end of treatment.The RSI score and SANDE scores significantly decreased(both P<0.001)after 1mo and at the end of treatment.CONCLUSION:The current,retrospective,and open study shows that combined therapy using Gastroftal eye drops and tablets could represent a valuable option in managing patients with DES associated with LPR.