Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

Effects of Electron Beam Local Postweld Heat Treatment on Microstructure and Properties of 30CrMnSiNi2A Steel Welded Joints

To improve the microstructure and properties of the electron beam welded joints, the vacuum or furnace whole post weld heat treatment (FWPWHT) usually should be done on it. The electron beam local post weld heat treatment (EBLPWHT) is a rather new heat treatment procedure that provides the advantages of high precision, flexibility and efficiency, energy saving and higher productivity. In this paper, the microstructure, mechanical properties, fracture toughness and fatigue properties of electron beam welded joints of 30CrMnSiNi2A steel in as-welded (AW) and EBLPWHT conditions have been investigated respectively. The results show that the microstructures of different zones of joints in as-welded condition are changed by EBLPWHT procedure, in which the welds from coarse needle martensite into lath-shaped martensite; the main structures of heat affected zones (HAZ) from lath-shaped martensite into lower bainite. The properties of welded joints can be improved by the EBLPWHT in some extent, especially the fracture toughness of the welds and the fatigue crack resistance of welded joints can be sufficiently improved. However, more appropriate heat treatment parameters of the EBLPWHT have to be studied in order to increase the mechanical properties of base metal near by the HAZ.

Temperature field analysis of main steam pipe under local post weld heat treatment

In local post weld heat treatment, the temperature difference is the criterion of the process. The temperature field in the main stream pipe under local post weld heat treatment is simulated by finite element method. A close-loop control program is designed to simulate the temperature field of two different pipes. Both the skin effect of induction heating and electro-thermal coupled effect are considered in the heating model. The local heat treatment temperature difference at the inner and outer side of the pipe is analyzed and the different convection conditions are also considered. The simulation results show that in appropriate induction heating process, the temperature difference in the pipe can be controlled within 30 ℃.

Contemporary management of locally advanced rectal cancer:Resolving issues, controversies and shifting paradigms

Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy（CRT） followed by total mesorectal excision（TME） reaches a plateau, the need for alternative strategies in locally advanced rectal cancer（LARC） has grown in relevance. Several novel strategies have been conceptualized to address this issue, including： 1） neoadjuvant induction and consolidation chemotherapy before CRT; 2） neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3） nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

NUMERICAL ANALYSIS OF RESIDUAL STRESSES IN TITANIUM ALLOY DURING ELECTRON BEAM LOCAL POST-WELD HEAT TREATMENT

The distributions of temperature and residual stresses in thin plates of BT20titanium alloy are numerically analyzed by three-dimensional finite element software duringelectron beam welding and electron beam local post-weld heat treatment (EBLPWHT). Combined withnumerical calculating results, the effects of different EBLPWHT mode and parameters, including heattreating position, heating width and heating time, on the distribution of welding residual stressesare analyzed. The results show that, the residual tensile stresses in weld center can be largelydecreased when the weld is heat treated at back preface of the plate. The numerical results alsoindicated that the magnitude of the residual longitudinal stresses of the weld and the zone vicinityof the weld is decreased, and the range of the residual longitudinal stresses is increased alongwith the increase of heating width and heating time.

TREATMENT OF LOCAL RECURRENCE OF NASOPHARYN-GEAL CARCINOMA WITH REIRRADIATION

From 1975 to 1987, 112 patients with loco-regional recurrence of nasopharyngeal carcinoma (N P C) were treated again with radiation at our hospital. All cases were proven histologically by biopsy. Of these patients, 92 had their recurrence in the nasopharynx only, 13 had additional involvement of the base of the skull, and 7 had tumor recurrences simultaneously in the nasopharynx as well as the cervical lymph nodes. Radiotherapy adopted in this series was 60Co external irradiation (X R Te) and/ or betatron in 96 patients, X R Te plus intracavitary 60Co irradiation (X R Ti) in 12 patients and X R Ti alone in the other 4 patients. The 1-, 3-, and 5-year survival rates were 86.3%, 45.8% and 30.2% respectively after the start of recurrence retreatment. The 63 patients who survived for 5 years or more were analyzed. The prognosis of the patient was related to the histological type, clinical stage, modality of treatment, and disease interval to recurrence and site of recurrence. No serious complications occurred. It is suggested that re-irradiation is appropriate in the treatment of loco-regional recurrent N P C.

THE FACTORS AND TREATMENT OF LOCAL RECURRENCE AFTER RADICAL RESECTION RESERVING THE ANUS IN THE PATIENTS WITH RECTAL CANCER

Of seventy-one patients with rectal cancer after radical resection retaining the anus, 15 developed local recurrence with a recurrence rate of 21.1%. Local recurrence was correlated with improper safety margin from the lower edge of cancer to the anal end. There was statistical significant difference between 3 cm or more and 2 cm or less. The local recurrence was also related to the pathologic stage, histologic differentiation and implant of free cancer cells. It is suggested that the surgical indication of saving the anus be strict and without stretching, the safety margin from the lower edge of cancer to the anal end should not be less than 2 cm in early rectal cancer and not less than 4 cm in advanced lesions. During the operation, no touching tumor technique, thorough rinsing of the peritoneal cavity and pre- or post-operative radiotherapy are important for prevention of local recurrence. Early local recurrent rectal cancer can be detected by periodic examinations.

Design and Optimization of Steel Car Body Structures via Local Laser-Strengthening

Continuously rising demands of legislators require a significant reduction of CO2-emission and thus fuel consumption across all vehicle classes. In this context, lightweight construction materials and designs become a single most important factor. The main engineering challenge is to precisely adapt the material and component properties to the specific load situation. However, metallic car body structures using “Tailored blanks” or “Patchwork structures” meet these requirements only insufficiently, especially for complex load situations (like crash). An innovative approach has been developed to use laser beams to locally strengthen steel crash structures used in vehicle bodies. The method tailors the workpiece hardness and thus strength at selected locations to adjust the material properties for the expected load distribution. As a result, free designable 3D-strengthening-patterns surrounded by softer base metal zones can be realized by high power laser beams at high processing speed. The paper gives an overview of the realizable process window for different laser treatment modes using current high brilliant laser types. Furthermore, an efficient calculation model for determining the laser track properties (depth/width and flow curve) is shown. Based on that information, simultaneous FE modelling can be efficiently performed. Chassis components are both statically and cyclically loaded. Especially for these components, a modulation of the fatigue behavior by laser-treated structures has been investigated. Simulation and experimental results of optimized crash and deep drawing components with up to 55% improved level of performance are also illustrated.

Local metothrexate treatment of cesarean scar ectopic pregnancy

Myometrial pregnancy developing in a previous caesarean section scar is the rarest of all ectopic pregnancies (EP) and probably one of the most dangerous of all because of the risk of rupture and hemorrhage. The recent recognition of this problem means that diagnosis and management are still in their infancy, and there is no consensus regarding the best management of CSP. Methotrexate (MTX) can be administered systemically or locally, or in both ways, with the aid of ultrasound. Patients diagnosed with caesarean scar pregnancies (CSP) in our clinic underwent transvaginal treatment of ectopic pregnancy. Safe and short treatment under transvaginal ultrasonographic (USG) guidance was performed uneventfully in all cases. The operating time ranged from 5 to 10 minutes with no blood loss. Serum β-hCG (β-subunit of human chorionic gonadotrophin) levels declined to normal levels within a month, and patients were discharged without further complications in two or three hours after the procedure. Our cases show that this treatment is effective, safe, and minimally invasive for patients diagnosed with CSP.

3D Finite Element Numerical Simulation of Residual Stresses on Electron Beam Welded BT20 Plates

A three-dimensional finite-element model (FEM) used for calculating electron beam (EB) welding temperature and stresses fields of thin plates of BT20 titanium has been developed in which the nonlinear thermophysical and thermo-mechanical properties of the material has been considered. The welding temperature field, the distributions of residual stresses in as-welded (AW) and electron beam local post-weld heat treatment (EBLPWHT) conditions have been successfully simulated. The results show that: (1) In the weld center, the maximum magnitude of residual tensile stresses of BT20 thin plates of Ti alloy is equal to 60%- 70% of its yield strength σs. (2) The residual tensile stresses in weld center can be even decreased after EBLPWHT and the longitudinal tensile stresses are decreased about 50% compared to joints in AW conditions. (3) The numerical calculating results of residual stresses by using FEM are basically in agreement with the experimental results. Combined with numerical calculating results, the effects of electron beam welding and EBLPWHT on the distribution of welding residual stresses in thin plates of BT20 have been analyzed in detail.

The role of a drug-loaded poly(lactic co-glycolic acid)(PLGA) copolymer stent in the treatment of ovarian cancer

Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.

Microstructure and fatigue crack growth behaviour of electron beam welding in 30CrMnSiNi2A steel

The effects of two post-weld heat treatment processes on the microstructure and fatigue properties of the electron beam welded joints of 30CrMnSiNi2A steel were studied. Electron beam local post-weld heat treatment (EBLPWHT), in a vacuum chamber, immediately after welding and a traditional furnace whole post-weld heat treatment (FWPWHT) were accepted. The experimental results show that, after EBLPWHT, the main microstructure of weld is changed from coarse acicular martensite into lath martensite, and base metal is changed from ferrite and perlite into upper bainite and residual austenite, however the microstructures of different zones of joints in FWPWHT conditions are tempered sorbite. The fatigue crack growth rate da/dN of welds and base metal are not obviously changed among EBLPWHT, FWPWHT test and as-welded (AW) test, as the mechanical properties of materials have a certain but not large effect on the da/dN of welded joints. The resistance to near threshold fatigue crack growth data of welded joints can be largely improved by EBLPWHT and it is related to microstructure and crack closure effect.

Recent update on comprehensive therapy for advanced hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.The treatment methods for HCC are diverse,mainly including surgical resection,ablation,and liver transplantation.The curative effect can be achieved only for early stage HCC,and it is easy to recur and metastasize after surgery,with a 5-year recurrence rate as high as 70%.Most patients with HCC are in the middle and advanced stage at the time of diagnosis and lose the chance of surgical resection.In recent years,with the in-depth study of the pathogenesis of HCC and the progress of medical science and technology,the systemic treatment of advanced HCC has made a breakthrough.At present,multidisciplinary comprehensive treatment including targeted therapy and immunotherapy has become an effective strategy and inevitable trend for the treatment of advanced HCC.Combined therapy has greatly improved the prognosis of HCC patients and opened up a new milestone in the treatment of this malignancy.In this article,we focus on the treatment progress of advanced HCC to further guide clinical practice.

Clinical outcomes of patients with duodenal adenocarcinoma and intestinal-type papilla of Vater adenocarcinoma

BACKGROUND Duodenal adenocarcinoma(DA)and intestinal-type papilla of Vater adenocarcinoma(it-PVA)are rare malignancies of the gastrointestinal tract.Current therapeutic options are translated nowadays from treatment strategies for patients with colorectal cancer due to histopathological similarities.AIM To retrospectively investigate the clinical outcome of patients with DA and it-PVA.METHODS All patients with DA and it-PVA diagnosed between 2000 and 2017 were included at two academic centers in the Netherlands.All patients with histopathologically-confirmed DA or it-PVA were eligible for inclusion.Clinical outcome was compared between DA and it-PVA per disease stage.In the subgroup of stage IV disease,survival after local treatment of oligometastases was compared with systemic therapy or supportive care.RESULTS In total,155 patients with DA and it-PVA were included.Patients with it-PVA more often presented with stage I disease,while DA was more often diagnosed at stage IV(P<0.001).Of all patients,79%were treated with curative intent.The median survival was 39 mo,and no difference in survival was found for patients with DA and it-PVA after stratification for disease stage.Seven(23%)of 31 patients with synchronous stage IV disease underwent resection of the primary tumor,combined with local treatment of oligometastases.Local treatment of metastases was associated with an overall survival of 37 mo,compared to 14 and 6 mo for systemic therapy and supportive care,respectively.CONCLUSION Survival of patients with DA and it-PVA is comparable per disease stage.These results suggest a potential benefit for local treatment strategies in selected patients with oligometastases,although additional prospective studies are needed.

Pulsed-Laser Annealing of NiTi Shape Memory Alloy Thin Film

Local annealing of amorphous NiTi thin films was performed by using an Nd：YAG 1064 nm wavelength pulsed laser beam. Raw samples produced by simultaneous sputter deposition from elemental Ni and Ti targets onto unheated Si （100） and Silica （111） substrates were used for annealing. Delicate treatment with 15.92 W/mm^2 power density resulted in crystallization of small spots; while 16.52 and 17.51 W/mm^2 power densities caused ablation of the amorphous layer. Optical microscopy, scanning electron microscopy, X-ray diffraction and atomic force microscopy were performed to characterize the microstructure and surface morphology of the amorphous/crystallized spot patterns.

Injectable thermo-responsive nano-hydrogel loading triptolide for the anti-breast cancer enhancement via localized treatment based on “two strikes” effects

The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient delivery.Herein,a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL.Based on the amphiphilic structure of poly(N-isopropylacrylamide-co-acrylic acid)-g-F68 copolymer,it was able to form nano-micelles to efficiently encapsulate TPL,and then turn into a hydrogel at 37C.TPL@nano-gel exhibited a sustained drug release profile in vitro and a stronger anticancer effect caused by"two strikes".The"first strike"was its enhanced cytotoxicity compared to free TPL,due to the enhanced pro-apoptosis effect observed in both MDA-MB-231 and MCF-7 cells caused by the regulation of endogenous mitochondrial pathways.Furthermore,TPL@nano-gel exhibited a"second-strike"through its anti-angiogenesis capabilities mediated through VEGFR-2 signaling inhibition.As expected,after intra-tumoral injection at a 0.45 mg/kg TPL-equivalent dose three times over 14 days in 4 T1 tumor-bearing mice,TPL@nano-gel led to lower systemic toxicity and higher antitumor efficacy compared to multiple injections of TPL.In this regard,these findings indicate that this injectable thermo-responsive hydrogel carries great potential for TPL as a safe and effective cancer therapy.

Local treatment of osteoporosis with alendronate-loaded calcium phosphate cement

Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures.We term this strategy as the ＂local treatment of osteoporosis＂.The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement （CPC） as a novel drug delivery system for local treatment of osteoorosis.Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate （ALE,0,2,5,10 weight percent （wt％））.The microstructure,setting time,infrared spectrum,biomechanics,drug release,and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE.An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups：normal,Sham （ovariectomized （OVX） ＋ Sham）,CPC with 2％ ALE,5％ALE,and 10％ ALE groups.At 4 months after the implantation of the composite,animals were sacrificed and the caudal vertebrae （levels 4-7） were harvested for micro-CT examination and biomechanical testing.Results The setting time and strength of CPC was significantly faster and greater than the other groups.The ALE release was sustained over 21 days,and the composite showed good biocompatibility.In micro-CT analysis,compared with the Sham group,there was a significant increase with regard to volumetric bone mineral density （BMD） and trabecular number （Tb.N） in the treated groups （P ＜0.05）.Trabecular spacing （Tb.Sp） showed a significant increase in the Sham group compared to other groups （P ＜0.01）.However,trabecular thickness （Tb.Th） showed no significant difference among the groups.In biomechanical testing,the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro,which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.

The survival and prognostic factors of primary testicular lymphoma- two-decade single-center experience

This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma （PTL） patients. We retrospectively reviewed the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis. The Kaplan-Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival （PFS）, overall survival （OS）, and determine prognosis predictors. The median follow-up time was 30 months. Median OS and PFS were 96 months and 49 months, respectively. In univariate analysis, advanced Ann Arbor stage （Ill/IV） （P 〈 0.001）, B symptoms （P 〈 0.001）, and extranodal involvement other than testis （P = 0.001） were significantly associated with shorter OS and PFS. In multivariate analysis, Ann Arbor stage was significantly associated with OS （OR = 11.58, P = 0.049）, whereas B symptom was significantly associated with PFS （OR = 11.79, P = 0.049）. In the 10 patients with the systemic usage of rituximab, bilateral intervention could improve median OS from 16 to 96 months （P = 0.032）. The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.

NUMERICAL MODELLING OF FREE-SURFACE FLOWS WITH BOTTOM AND SURFACE-LAYER PRESSURE TREATMENT

A new non-hydrostatic numerical model with the three-dimensional Navier-Stokes equations on structured grids was constructed and discussed. The algorithm is based upon a staggered finite difference Crank-Nicholson scheme on a Cartesian grid. The eddy viscosity coefficient was calculated by the efficient k-ε turbulence model. A new surface-layer non-hydrostatic treatment and a local cell bottom treatment were introduced so that the three-dimensional model is fully non-hydrostatic and is free of any hydrostatic assumption. The developed model is second-order accuracy in both time and space when semi-implicit coefficient is set to 0.5. The validity of the present solution algorithm was demonstrated from its application to the three-dimension channel flow and the wave propagation over a submerged bar problems.

DOX/IL-2/IFN-g co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment

Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.