Development and Validation of Liquid Chromatographic Method for the Determination of the Related Substances of Rifampicin

A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.

Validated gradient stability indicating HPLC method for determining Diltiazem Hydrochloride and related substances in bulk drug and novel tablet formulation

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.

Analysis of bacitracin and its related substances by liquid chromatography tandem mass spectrometry

A suitable liquid chromatography quadrupole time-of-flight mass spectrometric(LC–Q-TOF–MS) method was developed for separation and characterization of related substances in bacitracin test drug. The separation was performed on Li Chrospher RP-18 column using methanol as mobile phase A and 0.2% ammonium acetate buffer solution as mobile phase B in gradient elution. A total of 12 related substances were detected through high resolution mass spectrometric determination in a positive electrospray ionization mode. They were identified as co-existing active components and degradation products of bacitracin through the analysis and elucidation of both the protonated parents and the product ions of all the related substances and their fragmentation pathways were also proposed.

Analysis of ganciclovir and its related substances using high performance liquid chromatography and liquid chromatography-mass spectrometry methods

Objective High performance liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC/MS)methods were developed for the determination of ganciclovir and its related substances.Methods A Hypersil ODS2 column(4.6 mm×250 mm,5 μm)was used with a mobile phase of 0.02 M potassium dihydrogen phosphate buffer(pH 6.0)-methanol(92∶8)at a flow rate of 1.0 mL/min,and UV detector set at 254 nm was used for monitoring the eluents.Results The method was simple,rapid,selective and capable of separating all related substances at trace level with a detection limit of 0.04 μg/mL.It has been validated with respect to accuracy,precision,linearity,and limits of detection and quantification.The linearity range was 10.2-153.0 μg/mL with r=0.9998.The percentage recoveries ranged from 96.7% to 101.6%,and RSD was 1.24%-1.96%(n=5).Conclusion The method was found to be suitable not only for monitoring the reactions during the process development but also for quality control of ganciclovir.For identification of related substances,LC/MS was used.The mainly related substances of ganciclovir active pharmaceutical ingredients(API)were determined as guanine,(1,3-dioxolan-4-yl)methyl acetate,and diacetyl guanine.

Determination of 9-Deoxo-9a-Aza-9a-Homoerythromycin A and Related Substances by High-Performance Liquid Chromatography

A high-performance liquid chromatography（HPLC） method was developed and validated for the assay of 9-deoxo-9a-aza-9a-homoerythromycin A and related substances that might coexist in products as impurities that originate from the synthesis processes. A chromatographic system comprising an ODS 150 mm× 4.6 mm I.D. column, a mobile phase of cetonitrile monobasic potassium phosphate buffer （25/75）, a flow rate of 1.2 mL/min, a temperature of 30 ℃and a UV detector set at 205 nm has shown good chromatographic separation for 9-deoxo-9a-aza-9a-homoerythromycin A and other related substances. The linearity of the calibration curves, the precision, expressed as relative standard deviations, of the HPLC method have been studied. The HPLC method under study was found to be specific, precise, accurate and reproducible, indicating stability.

Identification and characterization of related substances in EVT-401 by hyphenated LC–MS techniques

A sensitive and selective method was developed for the separation and characterization of related substances(RSs) in EVT-401 by hyphenated LC–MS techniques. Complete separation of the RSs was achieved with an Inertsil ODS-SP column(250 mm×4.6 mm, 5 μm) by linear gradient elution using a mobile phase consisting of 0.2% formic acid solution, methanol and acetonitrile. EVT-401 was found to be susceptible to acid, alkaline and oxidative stresses, while relatively stable under photolytic and thermal dry stress conditions. Fourteen RSs including six process-related substances and eight degradation products were detected and identified in EVT-401 with positive ESI high-resolution TOF-MS analysis of their parent ions and the corresponding product mass spectra elucidation, and some of them were further verified by chemical synthesis and NMR spectroscopy. The specific LC–MS method developed for separation, identification and characterization of RSs is valuable for EVT-401 manufacturing process optimization and quality control.

LC-MS/MS Method Applied to the Detection and Quantification of Ursodeoxycholic Acid Related Substances in Raw Material and Pharmaceutical Formulation

Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.

Analytical method development of pregabalin and related substances in extended release tablets containing polyethylene oxide

Pregabalin,(S)-3-amino methyl hexanoic acid,is a structural analogue ofγ-amino butyric acid(GABA)which has been widely used to treat partial seizures and neuropathic pain[1].It is soluble in aqueous solution and sparingly soluble in organic solvents such as ethanol,DMSO and DMF.Polyethylene oxide(PEO)has a strong negative effect on analysis of hydrophilic active ingredient and its relative substances due to extremely high viscosity of PEO in aqueous media.The aim of this study is to develop a fast and precise method for the determination of pregabalin and its relative substances in extended release tablets including PEO using sodium sulfate for the treatment of sample solution.

Correlation of gut microorganisms and non-volatile flavor substances provides new insights for breeding Scylla paramamosain

The farming of Scylla paramamosain with specific flavors has a higher commercial value,and the flavors are related to the integrated farming environment and non-volatile flavor substances,while the survival environment is one of the important ways to source gut microorganisms in the organism.In this study,the levels of dominant taxa in the gut flora of S.paramamosain from Mong Cai,Vietnam(VN),Taishan City,Guangdong Province(TS)of China,and Ninghai County,Ningbo City(NB)Zhejiang Province of China converged with those of S.paramamosain from Sanmen County,Ningbo City(CK 1,CK 2,and CK 3)at 28 d of domestication.The top 15 genera with the highest abundance of VN,TS,and NB gut flora were the same as CK 1,CK 2,and CK 3,but with different percentages,and gradually converged to CK 1,CK 2,and CK 3,respectively,at 28 d of domestication.Correlation between intestinal flora and non-volatile flavor substances in the hepatopancreas at the percentage level of relative abundance of bacterial genera found that above 28 d of domestication,Muribaculaceae,Psychrilyobacter,Clostridia_vadinBB 60_group,Halarcobacter Carboxylicivirga,Sediminispirochaeta may be the most important genera affecting flavor amino acids of VN.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Psychrilyobacter,and Pseudomonas may be the most important genera affecting flavor amino acids of NB.Sediminispirochaeta,Carboxylicivirga,Halarcobacter,Photobacterium,ZOR 0006,Vibrio,and Sphingomonas may be the most important genera affecting flavor amino acids of TS.These results show that the intestinal flora structure of crabs from different areas were domesticated in the same area for at least 28 d before they converged to that of the domesticated crab,and the most important genera affecting the flavor amino acids of TS,VN,and NB were also identified.The results of this study provide a reference and basis for the technique of directional cultivation of the flavor quality of the crab.

Occurrence,Spatial Distribution,Sources and Risk Assessment of Per-and Polyfluoroalkyl Substances in Surface Sediments of the Yellow River Delta Wetland

Per-and polyfluoroalkyl substances(PFASs)are emerging persistent organic pollutants(POPs).In this study,47 surface sediment samples were collected from the Yellow River Delta wetland(YRDW)to investigate the occurrence,spatial distribution,potential sources,and ecological risks of PFASs.Twenty-three out of 26 targeted PFASs were detected in surface sediment samples from the YRDW,with totalΣ23PFASs concentrations ranging from 0.23 to 16.30 ng g^(-1) dw and a median value of 2.27 ng g^(-1) dw.Perfluorooctanoic acid(PFOA),perfluorobutanoic acid(PFBA)and perfluorooctanesulfonic acid(PFOS)were the main contaminants.The detection frequency and concentration of perfluoroalkyl carboxylic acids(PFCAs)were higher than those of perfluoroal-kanesulfonic acids(PFSAs),while those of long-chain PFASs were higher than those of short-chain PFASs.The emerging PFASs substitutes were dominated by 6:2 chlorinated polyfluoroalkyl ether sulfonic acid(6:2 Cl-PFESA).The distribution of PFASs is significantly influenced by the total organic carbon content in the sediments.The concentration of PFASs seems to be related to human activities,with high concentration levels of PFASs near locations such as beaches and villages.By using a positive matrix factorization model,the potential sources of PFASs in the region were identified as metal plating mist inhibitor and fluoropolymer manufacturing sources,metal plating industry and firefighting foam and textile treatment sources,and food packaging material sources.The risk assessment indicated that PFASs in YRDW sediments do not pose a significant ecological risk to benthic organisms in the region overall,but PFOA and PFOS exert a low to moderate risk at individual stations.

The Prevalence of Overweight/Obesity and Related Comorbidities among HIV-Positive and HIV-Negative Patients Attending the Same Clinics in Gaborone, Botswana

Context: Antiretroviral therapy (ART) helps restore the health status of people living with HIV (PLHIV). Likewise, it increases the risk of overweight/obesity and related comorbidities among the recipients. In countries like Botswana where ±84% of PLHIV is on ART, the paucity of data comparing overweight/obesity between HIV-positive on ART and HIV-negative patients may impede clinical and policy decision-making. This study sought to estimate and compare: i) the prevalence of overweight/obesity between HIV-positive on ART and HIV-negative patients;ii) the prevalence of hypertension (HTN), diabetes mellitus (DM)/coronary heart disease (CHD) between HIV-positive patients on ART and HIV-negative patients attending same outpatient departments of general clinics in Gaborone, Botswana. Patients and Methods: Five hundred eighty-one (581) outpatients were recruited in four major clinics of Gaborone, Botswana, between June and July 2019;294 or 51% of them were HIV-negative and 287 or 49% were HIV-positive on ART. The prevalence of overweight/obesity and of HTN and DM/CHD were calculated and examined using stratified analysis. Subgroups were compared using Chi-square analysis with Yates correction or Fisher exact test and t-student test for continuous data. Results: Major findings after stratification of the study population by HIV status were: i) the prevalence of all categories of (BMI), including overweight/obesity, were comparable between HIV-negative-patients and HIV-positive. In fact, there were 24 (8.0%) cases of underweight among HIV-negative-Patients and 15(5%) cases among HIV-positive patients, p = 0.2;145 (49%) HIV-negative-patients and 128 (45%) HIV-positive, p = 0.07 cases of normal weight;72 (25%) HIV-negative-patients and 87 (30%) HIV-positive, p = 0.08, were overweight;53 (18%) HIV-negative-patients and 57 (20%) HIV-positive, p = 0.12, were obese;125 (43%) HIV-negative patients and 144 (50%) HIV-positive, p=0.06 were overweight/obese;ii) the prevalence of HTN and DM/CHD among HIV-positive-patients were significantly lower (p < 0.05) compared to HIV-negative patients: There were 32 (10.9%) cases of HTN among HIV-negative patients compared to 18 (6.3%) cases of HTN among HIV-positive patients, p = 0.001;32 (11%) cases of DM/CHD HIV-negative patients compared to 4 (1.4%) cases of DM/CHD among HIV-positive patients, p = 0.001. Conclusion: the prevalence of overweight/obesity observed between HIV-negative and HIV-positive patients may suggest that the two groups shared the same exposure factors. That HTN and DM/CHD prevalence was lower among HIV-positive compared to HIV-negative patients, is possibly due to interplay factors of ART, HIV or the host population. Further studies are, however, recommended for clarifications.

Research Progress of Volatile Substances Analysis and Sensory Evaluation of Soymilk

Soybean is one of the important crops in China. Soymilk, a traditional neutral plant-based protein drink, is rich in high quality proteins. Although soybean milk is rich in nutrients, its marketing among consumers, especially those in Western countries who are used to peaceful flavor, has been limited due to the adverse flavor impact brought by its special composition. In recent years, with the increasing attention to the nutritional value of soymilk, the flavor of soymilk has become a popular research object for scholars at home and abroad. The flavor components of soymilk are mainly volatile small molecular compounds produced by enzymatic reactions catalyzed by lipoxygenase(LOX). After formation, they interact with protein macromolecules to form the overall flavor of soymilk. At present, there are many methods to control the off-odor of soymilk at home and abroad, including physical heating methods, chemical methods, biological enzymatic digestion methods, mask methods, and a variety of breeding methods. These methods effectively reduce the off-odor of soymilk, but all of them have shortcomings. Currently, the sensory characteristics of the beany odor in soymilk are evaluated mainly by traditional human sensory scoring along with the assistance of modern instrument analysis of volatile flavor substances using headspace solid phase microextraction(SPME) gas chromatography coupled with-mass spectrometry(GC-MS). This paper summarized the research results of volatile flavor substances in soymilk in recent years and the sensory evaluation methods of soymilk at home and abroad, and looked forward to the future development direction, hoping to provide some theoretical bases and reference detection methods for solving the problem of soymilk flavor in the future.

Evaluation of Rhizobium tropici-Derived Extracellular Polymeric Substances on Selected Soil Properties, Seed Germination, and Growth of Black-Eyed Peas (Vigna unguiculata)

Rhizobium tropici-derived extracellular polymeric substances (EPS) have been used in soils to enhance soil structures and mitigate soil erosions. However, information on their use to improve soil health and fertility indicators, and plant growth is limited. In a greenhouse study, we investigated their effects on some soil health, soil fertility indices, and the growth of black-eyed peas (Vigna unguiculate). Results showed that soils incubated with EPS significantly increased basal soil respiration, soil microbial biomass, permanganate oxidizable carbon (POC), and potentially mineralizable nitrogen (PMN). The EPS shifted microbial populations from bacteria to fungi and Gram (−ve) to Gram ( ve) bacteria. However, it had little or no effects on soil pH, soil organic matter (SOM), and cation exchange capacity (CEC). The EPS decreased soil moisture loss, increased soil aggregate stability, but delayed blacked-eyed peas germinations in the soils. At 0.1% (w/w) concentrations in soils, there was increase in plant root nodulations and vegetative growth. This study was carried out within 40 days of incubating soils with EPS or growing the black-eyed peas in a greenhouse study. The plant growth parameters were taken before flowering and fruiting. Further studies of the effects of incubating soils with the extracellular polymeric substances on plant growth. Soil microbial biomass, microbial diversities, and other soil fertility indices are deemed necessary.

Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune cells.Developing precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial drugs.This,in turn,holds the potential to mitigate the alarming issue of bacterial drug resistance.Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds.Considering the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric materials.This ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches.In this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions.Additionally,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric methods.Furthermore,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges.This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm formation.This insight opens up a new avenue for exploration within this research domain.

Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Evaluation of internal void related defects in reinforced concrete slab using electromagnetic wave properties

This study aims to develop a damage-detection algorithm based on the electromagnetic wave properties inside a reinforced concrete structure.The proposed method involves employing two algorithms based on data measured using ground-penetrating radar—a common electromagnetic wave method in civil engineering.The possible defect area was identified based on the energy dissipated by the damage in the frequency-wavenumber domain,with the damage localized using the calculated relative permittivity of the measurements.The proposed method was verified through a finite difference time-domain-based numerical analysis and a testing slab with artificial damage.As a result of verification,the proposed method quickly identified the presence of damage inside the concrete,especially for honeycomb-like defects located at the top of the rebar.This study has practical significance in scanning structures over a large area more quickly than other non-destructive testing methods,such as ultrasonic methods.

The Impact of Finerenone on Changes in Pulse Wave Velocity, Arterial Pressure and Heart Related Deaths in Hemodialysis Patients—Study Perspective

The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.

A Germplasm Resource Repository:The Book Review of Illustrated Flora of Food Crops and Their Wild Related Plants in China

Illustrated Flora of Food Crops and Their Wild Related Plants in China systematically examines the botanical and morphological characteristics of China's major food crops,such as rice,wheat,corn,sweet potato,potato,mung bean,and buckwheat.Featuring more than 5000 color photos and 200 line drawings,it offers a comparative study that highlights the kinship and internal connections between cultivated and wild species.The book is an invaluable resource for breeders,offering a comprehensive morphological and genetic database that aids in the development of high-yielding,high-quality,and disease-resistant crop varieties.

Preserving the Ozone Layers: Battling Illegal Trade in Ozone-Depleting Substances

The depletion of the ozone layer, a vital shield protecting the Earth from harmful ultraviolet (UV) radiation, is now a worldwide environmental concern. Human activities, particularly the release of ozone depleting substances (ODS), have led to the thinning of this protective layer over recent decades. Simultaneously, illegal trade has emerged as a global challenge, giving rise to economic issues, losses of tax revenue, heightened criminal activities, health risks, and environmental hazards. The depletion of the ozone layer, a critical shield protecting the Earth from harmful ultraviolet (UV) radiation, has become a global environmental concern. This paper delves into the legal dimensions surrounding ozone-depleting substances (ODS), their impact on the ozone layer, and the subsequent risk of skin cancer. As countries navigate international agreements, domestic regulations, and enforcement mechanisms, the intricate interplay between legal frameworks and the health implications of ozone layer depletion comes to the forefront. The paper highlights particular instances of illegal trade in ozone depleting substances, drawing from data reported by the parties to the Montreal Protocol. Notably, China stands out as a significant source of contraband ODS, with other countries such as Bulgaria, Lithuania, Poland, and France reporting numerous cases. Analyzing these case instances offers insights into the efficacy of legal frameworks and enforcement measures. The paper offers a comprehensive set of recommendations to strengthen global control and enforcement against the illegal trade of ozone depleting substances. These recommendations span diverse aspects such as production monitoring, customs collaboration, mutual verification, cross-border agreements, public-private partnerships, international cooperation, detection equipment, global regulatory standards, resource allocation, public awareness campaigns, alternative substance development, and controlling the trade at its source. By applying these recommendations and enhancing enforcement measures, we aim to protect the ozone layer and create a healthier and safer world for future generations and achieve sustainable development goals.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.