Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma(aGC),it may lead to an adverse prognosis.Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients.AIM To determine the efficacy and safety of cetuximab(CET)combined with the FOLFOX4 regimen(infusional fluorouracil,folinic acid,and oxaliplatin)as firstline therapy for patients with aGC,who received evidence-based care(EBC).METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled.Of these,60 in the research group(RG)received CET+FOLFOX4 as first-line therapy,whereas 57 in the control group(CG)received FOLFOX4.The efficacy[clinical response rate(RR)and disease control rate(DCR)],safety(liver and kidney dysfunction,leukopenia,thrombocytopenia,rash,and diarrhea),serum tumor marker expression[STMs;carbohydrate antigen(CA)19-9,CA72-4,and carcinoembryonic antigen(CEA)],inflammatory indicators[interleukin(IL)-2 and IL-10],and quality of life(QOL)of the two groups were compared.RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG,with an equivalent safety profile between the two groups.RG exhibited notably reduced CA19-9,CA72-4,CEA,and IL-2 levels following treatment,which were lower than the pre-treatment levels and those in the CG.Post-treatment IL-10 was statistically increased in RG,higher than the pre-treatment level and the CG.Moreover,a significantly improved QOL was evident in the RG.CONCLUSION The CET+FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC.It facilitates the suppression of STMs,ameliorates the serum inflammatory microenvironment,and enhances QOL,without increased adverse drug effects.

Clinical Effects of the Follicular Phase Long Regimen and Luteal Phase Long Regimen on Ovulation Induction in IVF-ET Treatment: A Meta-Analysis

Objective:To systematically evaluate the clinical effects of the follicular phase long regimen and the luteal phase long regimen on ovulation induction in IVF-ET treatment.Methods:Databases including PubMed,Embase,Cochrane Library,CNKI,Chinese Biomedical Literature(CBM),VIP,Wanfang,and others were searched up to January 2021.Clinical studies on ovulation induction using the follicular phase long regimen and luteal phase long regimen in IVF-ET treatment were identified.Literature screening,data extraction,and quality evaluation were conducted based on inclusion and exclusion criteria.Meta-analysis was performed using RevMan 5.3 software.Results:After screening,a total of 11 studies were included,comprising 21,544 patients:9,974 in the follicular phase long regimen group and 11,570 in the luteal phase long regimen group.The meta-analysis results were as follows:(1)The number of Gn days and the total amount of Gn in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05);(2)The number of eggs obtained in the follicular phase long regimen was higher than that in the luteal phase long regimen(P<0.05).There were no significant differences in the rate of embryo optimization and cycle cancellation between the two groups(P>0.05);(3)The embryo implantation rate and clinical pregnancy rate in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05),while the abortion rate in the follicular phase long regimen was lower than that in the luteal phase long regimen(P<0.05).Conclusion:Compared to the luteal phase long regimen,the follicular phase long regimen involves more Gn days and a higher total amount of Gn.The optimal embryo rate and cycle cancellation rate were similar between the regimens,but the follicular phase long regimen resulted in more eggs,significantly improved the implantation and clinical pregnancy rates,and reduced the abortion rate.However,these conclusions require further validation through more multicenter,large-sample RCT studies.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Adjusting phosphate feeding regimen according to daily rhythm increases eggshell quality via enhancing medullary bone remodeling in laying hens

Background Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle.The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms.There is lack of information about the impact of adjusting phosphate feeding regimen according to daily rhythm on the phosphorus homeostasis and bone remodeling of laying hens.Methods and results Two experiments were conducted.In Exp.1,Hy-Line Brown laying hens(n=45)were sampled according the oviposition cycle(at 0,6,12,and 18 h post-oviposition,and at the next oviposition,respectively;n=9 at each time point).Diurnal rhythms of body calcium/phosphorus ingestions and excretions,serum calcium/phosphorus levels,oviduct uterus calcium transporter expressions,and medullary bone(MB)remodeling were illustrated.In Exp.2,two diets with different phosphorus levels(0.32%and 0.14%non-phytate phosphorus(NPP),respectively)were alternately presented to the laying hens.Briefly,four phosphorus feeding regimens in total(each included 6 replicates of 5 hens):(1)fed 0.32%NPP at both 09:00 and 17:00;(2)fed 0.32%NPP at 09:00 and 0.14%NPP at 17:00;(3)fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00;(4)fed 0.14%NPP at both 09:00 and 17:00.As a result,the regimen fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00,which was designed to strengthen intrinsic phosphate circadian rhythms according to the findings in Exp.1,enhanced(P<0.05)MB remodeling(indicated by histological images,serum markers and bone mineralization gene expressions),elevated(P<0.05)oviduct uterus calcium transportation(indicated by transient receptor potential vanilloid 6 protein expression),and subsequently increased(P<0.05)eggshell thickness,eggshell strength,egg specific gravity and eggshell index in laying hens.Conclusions These results underscore the importance of manipulating the sequence of daily phosphorus ingestion,instead of simply controlling dietary phosphate concentrations,in modifying the bone remodeling process.Body phosphorus rhythms will need to be maintained during the daily eggshell calcification cycle.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Evaluation of <i>In-Vitro</i>Anti-Tuberculosis Activity of <i>Tetrapleura tetraptera</i>Crude and Fractions on Multidrug Resistant <i>Mycobacterium tuberculosis</i>

The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of Tetrapleura tetraptera against Mycobacterium tuberculosis and MDR-TB and the phytochemical present. The leaves of Tetrapleura tetraptera were collected, weighed, dried and pulverized to powder. The pulverized leaves of Tetrapleura tetraptera were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques. M. tuberculosis and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible M. tuberculosis and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that Tetrapleura tetraptera crude had activities against M. tuberculosis at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of M. tuberculosis at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. T. tetraptra possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

SARS-COV-2 Infection and Anti-Tuberculosis Immunity: Temporal Association or Real Protective Role?

Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies;it would have large positive repercussions for developing countries.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

Early efficacy of individual regimens containing bedaquiline in patients with drug resistant tuberculosis

Objective:To evaluate early efficacy of sputum conversion within 6 months of individual regimens containing bedaquiline in patients with drug resistant tuberculosis.Methods:We conducted a retrospective study among patients with drug resistant tuberculosis who were receiving individual regimens containing bedaquiline.The primary outcome was sputum conversion of both smear and culture within 6 months of treatment.We used medical records of drug resistant tuberculosis patients from January 2020 to December 2021.The study was conducted at Dr.Soetomo Hospital,Indonesia from August to October 2022.Results:In this study,44 eligible drug resistant tuberculosis patients were initiated on regimens containing bedaquiline.There were 52.3%males and the median age was 45.5 years.The rates of previous treatment(70.5%)and lung cavity(36.4%)were high.The most common companion drugs included clofazimine,cycloserine,levofloxacin,and linezolid.Sputum smear and culture conversion was seen in 79.4%and 82.1%at the 2nd month,respectively.More than 97%patients had smear and culture conversion at the end of 6 months.Conclusions:Among drug resistant tuberculosis patients,individual regimens containing bedaquiline were associated with high rates of smear and culture conversion at the end of 6 months.Early efficacy of regimens containing bedaquiline can be used to predict cure rate at the end of treatment.

The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

含多西环素和左氧氟沙星的四联补救方案治疗幽门螺杆菌初次根除失败患者的临床效果研究

目的探究含多西环素、左氧氟沙星的四联补救方案治疗幽门螺杆菌(Hp)初次根除失败患者的临床效果。方法选择广西壮族自治区玉林市第一人民医院自2021年1月至2023年2月收治的166例Hp初次根除失败患者进行临床研究,采用随机数字表法分为对照组和观察组,各83例。对照组患者采用含左氧氟沙星的四联补救方案治疗,观察组患者采用含多西环素、左氧氟沙星的四联补救方案治疗,2组均连续治疗14 d。比较2组患者治疗总有效率、Hp根除率、上腹部胀痛、腹痛、嗳气、反酸等临床症状积分、血清炎症因子水平、免疫功能指标、治疗成本效益及不良反应发生率。结果观察组治疗后总有效率及Hp根除率均高于对照组[98.8%(82/83)比81.9%(68/83)、97.6%(81/83)比80.7%(67/83)],差异均有统计学意义(P<0.05)。治疗后,观察组上腹部胀痛、腹痛、嗳气、反酸临床症状积分,血清炎症因子C反应蛋白、肿瘤坏死因子α、白细胞介素6及白细胞介素8水平均低于对照组(P<0.05)。治疗后,观察组CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)比值高于对照组,CD_(8)^(+)水平低于对照组(均P<0.05)。观察组治疗成本效益优于对照组(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P=0.915)。结论含多西环素、左氧氟沙星的四联补救方案治疗Hp初次根除失败患者的临床效果显著,能快速缓解患者躯体不适症状和炎症反应,提高其免疫力及Hp根除率,且药物安全性高,治疗成本效益更优。

贝达喹啉联合背景方案治疗耐药肺结核的疗效

目的:探讨贝达喹啉联合背景方案治疗耐药肺结核的疗效。方法:回顾性选择2022年1月至2023年1月广东省广州市胸科医院收治的159例耐药肺结核患者,按随机对照原则分组。对照组(80例)接受常规背景方案治疗,研究组(79例)在其基础上联合贝达喹啉治疗。于6个月后评估两组病灶吸收率、痰菌转阴率及空洞闭合率,对比两组治疗前后血清肝功能指标、心电图QTc变化,统计两组不良反应发生率。结果:研究组病灶吸收率、痰菌转阴率及空洞闭合率均较对照组高(P<0.05)。两组治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平升高(P<0.05);研究组治疗后ALT、AST水平与对照组相比,差异无统计学意义(P>0.05)。两组治疗后QTcF值升高,心率降低(P<0.05)。且研究组治疗后QTcF值比对照组高,心率比对照组低(P<0.05)。两组转氨酶升高、白细胞减少及胃肠道反应发生率对比,差异无统计学意义(P>0.05);研究组QT间期延长发生率显著高于对照组(P<0.05)。结论:贝达喹啉联合背景方案治疗耐药肺结核的疗效较佳,未引起肝功能指标异常,但QT间期延长发生率较高。

通关藤注射液联合SOX方案治疗进展期胃癌临床观察

目的观察通关藤注射液联合SOX方案治疗进展期胃癌的疗效。方法将60例进展期胃癌患者随机分为对照组和观察组,每组30例。对照组患者接受标准SOX方案化学治疗;观察组患者加用通关藤注射液治疗。治疗前后分别检测患者血清癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原(carbohydrate antigen,CA)125、CA153、CA199水平,以及肝肾功能和血清白蛋白,并检测血小板、淋巴细胞、中性粒细胞、单核细胞计数及中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、血小板与淋巴细胞比值(platelet-to-lymphocyte ratio,PLR),采用卡氏功能状态量表(Karnofsky’s performance status,KPS)评价患者生活质量,比较两组患者总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)。结果观察组在降低血清CA125、CA199、PLR水平,提高KPS评分,防止血清白蛋白和淋巴细胞水平降低,延长OS和PFS方面均显著优于对照组(P<0.05)。结论通关藤注射液联合SOX方案治疗进展期胃癌具有增效减毒作用,可降低化学治疗药物不良反应,延长患者生存期。