Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.

Gastric cancer is one of the most common cancers and is considered the 5th most frequent occurring cancer worldwide. It has gained great attention from the clinicians and researchers because of high mortality rate. It is generally treated with chemotherapy, radiotherapy, and surgery. Recently, additional treatment options including immunotherapy and targeted therapy and immunotherapy have been developed. However, poor prognosis, limited survival rate of patients, and drug resistance to treatment remain critical problems. To improve treatment options or to overcome the bottleneck of treatment, identification of diagnostic and prognostic markers, determining the most effective therapeutic options, and uncovering the molecular regulations associated with treatment strategies are required. In this regard n6-methyladenosine (m6A) regulation is considered important. This reversible modification plays a crucial role in progression, development and treatment of HER2-positive gastric cancer. Here, we discuss the role of m6A modification in HER2-positive gastric cancer progression through collecting related studies at present. We further discuss the association of m6A modification with therapeutic efficacy in HER2-positive gastric cancer and list some examples. We conclude that modification of m6A can be a new strategy for improving the prognosis and survival rate of HER2-positive gastric cancer patients.

Trop2-targeted therapies in solid tumors: advances and future directions.

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.

Lipid-Based Nanocarrier by Targeting with LHRH Peptide: A Promising Approach for Prostate Cancer Radio-Imaging and Therapy.

Prostate cancer is a prevalently detected malignancy with a dismal prognosis. Luteinizing-hormone-releasing-hormone (LHRH) receptors are overexpressed in such cancer cells, to which the LHRH-decapeptide can specifically bind. A lipid-polyethylene glycol-conjugated new LHRH-decapeptide analogue (D-P-HLH) was synthesized and characterized. D-P-HLH-coated and anticancer drug doxorubicin (DX)-loaded solid lipid nanoparticles (F-DX-SLN) were formulated by the cold homogenization technique and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, differential scanning calorimetry, dynamic light scattering, electron microscopy, entrapment efficiency, and drug-release profile studies. F-DX-SLN allows site-specific DX delivery by reducing the side effects of chemotherapy. Cancer cells could precisely take up F-DX-SLN by targeting specific receptors, boosting the cytotoxicity at the tumor site. The efficacy of F-DX-SLN on PC3/SKBR3 cells by the MTT assay revealed that F-DX-SLN was more cytotoxic than DX and/or DX-SLN. Flow cytometry and confocal microscopic studies further support F-DX-SLNs' increased intracellular absorption capability in targeting LHRH overexpressed cancer cells. F-DX-SLN ensured high apoptotic potential, noticeably larger mitochondrial transmembrane depolarization action, as well as the activation of caspases, a longer half-life, and greater plasma concentration. F-DX-SLN/DX-SLN was radiolabeled with technetium-99m; scintigraphic imaging studies established its tumor selectivity in PC3 tumor-bearing nude mice. The efficacy of the formulations in cancer treatment, in vivo therapeutic efficacy tests, and histopathological studies were also conducted. Results clearly indicate that F-DX-SLN exhibits sustained and superior targeted administration of anticancer drugs, thus opening up the possibility of a drug delivery system with precise control and targeting effects. F-DX-SLN could also provide a nanotheranostic approach with improved efficacy for prostate cancer therapy.

Therapeutic efficacy and safety of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria treatment in Metehara, Central-east Ethiopia.

BACKGROUND: Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin, the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria. The World Health Organization (WHO) recommends regular surveillance of artemisinin therapeutic efficacy to inform policy decisions. METHODS: This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated P. falciparum malaria in Ethiopia since 2004. Using a single-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria in Metehara Health Centre, central-east Ethiopia. Out of 2332 malaria suspects (1187 males, 1145 females) screened, 80 (50 males, 30 females) were enrolled, followed up for 28 days, and 73 (44 males, 29 females) completed the follow up. The study was conducted and data was analysed by employing the per-protocol and Kaplan-Meier analyses following the WHO Malaria Therapeutic Efficacy Evaluation Guidelines 2009. RESULTS: The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitaemia and fever by day (D) 3. The prevalence of gametocytes decreased from 6.3% on D0 to 2.5% on D2, D3, D7, and ultimately achieving complete clearance afterward. CONCLUSION: The overall cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that AL remains a highly efficacious treatment for uncomplicated P. falciparum malaria in the study site after 20 years of its introduction in Ethiopia.

An update on the safety of lanreotide autogel for the treatment of patients with neuroendocrine tumors.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a rare group of tumors originating from neuroendocrine cells in various organs. They include neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which differ in biological behavior and prognosis. NETs are usually well-differentiated and slow-growing, while NECs are poorly differentiated and more aggressive. Management of NETs often involves somatostatin analogs like octreotide and lanreotide to control tumor growth and alleviate symptoms, especially in well-differentiated NETs. Lanreotide is used to control tumor growth, and both lanreotide and octreotide alleviate symptoms. Treatment approaches may vary depending on the specific type and grade of the neuroendocrine neoplasm. AREAS COVERED: This review provides an update on the safety of lanreotide autogel in treating patients with NETs, through a comprehensive review of clinical trials, post-marketing surveillance, real-world evidence, and its safety profile. Specific adverse events, side effects, and potential risks associated with lanreotide autogel are discussed, along with risk mitigation strategies and recommendations for patient monitoring. EXPERT OPINION: The findings highlight the overall safety of lanreotide autogel in managing NETs, focusing on its efficacy in controlling hormone secretion, tumor progression, and symptom management. New safety concerns and precautions are also addressed to help healthcare providers make informed decisions when prescribing lanreotide autogel.

Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction.

BACKGROUND: Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia. METHODS: In 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28. RESULTS: A total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h. CONCLUSION: Despite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.

A comparative analysis of sivelestat sodium hydrate and ulinastatin combination therapy in the treatment of sepsis with acute respiratory distress syndrome.

OBJECTIVE: This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS). METHODS: A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded. RESULTS: The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05). CONCLUSION: The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS.

Association between CD4+ T cells ATP levels and disease progression in patients with non­small cell lung cancer.

Introducing the exploration of stimulated CD4+ cells adenosine triphosphate (sATPCD4) levels for immune monitoring post non-small cell lung cancer (NSCLC) chemotherapy, the present study aimed to investigate its efficacy in gauging the potential risk of disease progression (PD) in patients with NSCLC. Therefore, a total of 89 patients with advanced NSCLC, who underwent chemotherapy between August 15 2022 and August 30 2023 at the Fifth Affiliated Hospital of Guangzhou Medical University (Guangzhou, China), were retrospectively studied. Patients were divided into the PD (n=21) and disease stability (non-PD; n=68) groups and their clinical data were compared. The thresholds for predicting PD were identified using receiver operating characteristics (ROC) curves. Multivariate logistic regression analysis was carried out to assess the association between peripheral blood markers and the incidence of PD. Therefore, post-chemotherapy, significant differences in white blood cell count, non-stimulated CD4+ cells ATP and sATPCD4 levels were obtained between patients in the PD and non-PD groups (P<0.05). In addition, sATPCD4 levels were notably decreased in the PD group compared with the non-PD group. Furthermore, ROC analysis revealed that the predictive threshold for PD was 224.5 ng/ml [area under the curve=0.887; 95% confidence interval, 0.811-0.963]. Additionally, patients with low immunity (ATP <224.5 ng/ml) exhibited a higher risk of PD compared with the high-immunity group (ATP >224.5 ng/ml; P<0.0001). Finally, multivariate logistic regression analysis suggested that sATPCD4 could serve as an independent factor for predicting NSCLC progression. Overall, the current study predicted that immune function could be possibly associated with the risk of PD in patients with NSCLC.

Beyond the Maze: Recent Advancements in Molecular and Cellular Tethered Drug Delivery Systems.

The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.

Analysis of vasoactive and oxidative stress indicators for evaluating the efficacy of continuous positive airway pressure, and relation of vasoactive and oxidative stress indicators and cardiac function in obstructive sleep Apnea Syndrome patients.

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a breathing disorder during sleep. The work was to evaluate the relationship between vasoactive and oxidative stress indicators and cardiac function in Obstructive Sleep Apnea Syndrome (OSAS) patients. Methods: OSAS patients (n=120) were treated with CPAP from May 2021 to June 2022. According to the clinical efficacy, the patients were divided into effective and ineffective groups. Vasoactive factors and oxidative stress indices were compared between the two groups to evaluate their clinical efficacy. The changes in cardiac function indices in the two groups were tested, and the correlation between vasoactive factors and oxidative stress indices and cardiac function was analysed. Results: The effective rate of CPAP was 63.33% (76/120). Ang II, ET-1, and MDA levels were lower, and the SOD level was higher in the effective group than in the ineffective group after treatment. The AUC of the four indicators was all greater than 0.75. LPWT and IVST values of the effective group were lower than the ineffective group. A positive correlation was identified between the levels of Ang II, ET-1, and MDA with LPWT, between levels of ET-1 and MDA with IVST, and a negative correlation between SOD with LPWT and IVST. Conclusions: CPAP treatment can effectively improve vascular activity and reduce the oxidative stress response in OSAS patients, and the combined detection of vasoactive factors and oxidative stress indicators is valuable for evaluating the efficacy of CPAP and is related to the cardiac function of patients.

Advancements in the use of nanopharmaceuticals for cancer treatment.

OBJECTIVE: Advances in nanotechnology make it possible to specifically target therapies to cancer cells and neoplasms, guide the surgical resection of tumors, and optimize the effectiveness of radiological treatments. This research article provides a concise synthesis of current knowledge in the field of galenic pharmacy focused on targeted drug delivery in oncology. This research article synthesizes current knowledge in galenic pharmacy, focusing on targeted drug delivery in oncology and reviewing recent advancements in nanopharmaceuticals for cancer treatment. DATA SOURCE: The data for this review are derived from a comprehensive analysis of the most cited scientific literature (Pubmed). Recent studies, clinical trials, and technological breakthroughs related to nanopharmaceuticals have been rigorously examined. This diverse source ensures a comprehensive representation of the latest developments in the field. SUMMARY OF DATA: The results highlight the emergence of nanopharmaceuticals as a promising approach to cancer treatment. The most common in oncology remain liposomes, nanopolymers, and nanocrystals. From a galenic point of view, these three forms offer a wide range of improvements compared to conventional forms such as improvement in solubility as well as stability. The same observation is in the clinic where treatment response rates are significantly improved. The most advantageous form will depend on the specific characteristics of each patient and each type of cancer. The precise design of nanocarriers allows for targeted drug delivery, enhancing therapeutic efficacy while reducing side effects. Concrete examples of clinical applications are presented, illustrating the practical potential of these advancements. CONCLUSION: In conclusion, this review provides a holistic overview of recent developments in galenic pharmacy for targeted drug delivery in oncology. The stability of nanocarriers is a crucial challenge because it conditions the effectiveness and safety of the drugs transported. Environmental and biological variations encountered in the body can compromise this stability, jeopardizing the therapeutic effectiveness and safety of treatments. Likewise, personalized approaches are essential to address interindividual variations in treatment response, as well as patients' pharmacogenomic profiles, in order to optimize therapeutic effectiveness and minimize adverse effects.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

Deciphering the Drug Delivery Potential of Milk Exosome Nanovesicles for Aminobenzylpenicillin Therapeutic Efficacy against Contagious Staphylococcus Aureus in Bovine Mastitis.

The emergence of antimicrobial resistance and failure of antibiotic treatment are challenging tasks for managing bovine mastitis, which is mainly caused by the contagious Staphylococcus aureus (S. aureus).To overcome these difficulties, there is an urgent need for a novel drug system. In the present study, the aim is to develop next-generation therapeutics against S. aureus by harnessing the drug delivery potential of milk nanovesicles called milk exosomes (mENs). In the present work, a drug system is developed by encapsulating aminobenzylpenicillin (AMP) in mENs (mENs-AMP). Electron microscopy and zeta-sizer results indicate that the size of mENs-AMP ranged from 55.79 ± 2.8 to 85.53 ± 7.4 nm. The AMP loading efficiency in mENs is 88.61% with its sustained release. Fluorescence spectroscopy results indicated that mENs are biocompatible with mammary epithelial cells. In vitro studies show that the antibacterial activity and the minimum inhibitory concentrations of mENs-AMP are eleven times greater and four times lower than that of unencapsulated AMP, respectively. The mENs-AMP exhibit significantly higher therapeutic efficacy than AMP at the same dosage and treatment frequency. Validation of this approach is demonstrated in mastitis-affected animals through an observation in the reduction of somatic cell counts and bacterial loads in the milk of treated animals.

Plasma Thioredoxin Reductase as a Potential Diagnostic Biomarker for Breast Cancer.

BACKGROUND: Early diagnosis of breast cancer is critical to the treatment and prognosis of breast cancer patients. Our aim is to explore more practical and effective diagnostic methods to facilitate early treatment and improve prognosis for breast cancer patients. MATERIALS AND METHODS: The Mann-Whitney U test, receiver operating characteristic curve, Youden index, Chi-square test, and Fisher's exact test were used to determine whether plasma thioredoxin reductase (TrxR) could be used for the clinical diagnosis of breast cancer. The Wilcoxon signed-rank test was used to validate the prognostic potential of plasma TrxR activity assessment. RESULTS: A total of 761 patients were included, including 537 cases of breast cancer and 224 cases of benign breast diseases. Plasma TrxR activity in the breast cancer group [8.0 (6.0, 9.45) U/mL] was significantly higher than that in the benign group [3.05 (1.20, 6.275) U/mL]. The diagnostic efficiency of TrxR for breast cancer was higher than that of other conventional breast cancer biomarkers, with an area under the curve of 0.821 (95% CI = 0.791-0.852). In addition, TrxR can be used in combination with conventional tumor markers to further improve the diagnostic efficiency. The optimal TrxR threshold for identifying benign and malignant diseases is 7.45 U/mL. We detected plasma TrxR activity and serum tumor markers before and after antitumor therapies in 333 breast cancer patients and found that their trends were basically the same, with a significant decrease in plasma TrxR activity after treatment. CONCLUSION: Plasma TrxR activity can be used as a suitable biomarker for breast cancer diagnosis and efficacy assessment.

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

Background: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

Therapeutic effect of curcumin nanoemulsion on cystic echinococcosis in BALB/c mice: a computerized tomography (CT) scan and histopathologic study evaluation.

BACKGROUND: This study aimed to determine the therapeutic efficacy of curcumin nanoemulsion (CUR-NE) in mice infected with Echinococcus granulosus sensu stricto protoscoleces. METHODS: Forty-two inbred BALB/c mice were divided into seven groups of six animals each. Six groups were inoculated intra-peritoneally with 1500 viable E. granulosus protoscoleces, followed for six months and used as infected groups. The infected groups were named as: CEI1 to CEI6 accordingly. The 7th group was not inoculated and was named cystic echinococcosis noninfected group (CENI7). CEI1 and CEI2 groups received 40 mg/kg/day and 20 mg/kg/day curcumin nanoemulsion (CUR-NE), respectively. CEI3 received nanoemulsion without curcumin (NE-no CUR), CEI4 received curcumin suspension (CUR-S) 40 mg/kg/day, CEI5 received albendazole 150 mg/kg/day and CEI6 received sterile phosphate-buffered saline (PBS). CENI7 group received CUR-NE 40 mg/kg/day. Drugs administration was started after six months post-inoculations of protoscoleces and continued for 60 days in all groups. The secondary CE cyst area was evaluated by computed tomography (CT) scan for each mouse before treatment and on the days 30 and 60 post-treatment. The CT scan measurement results were compared before and after treatment. After the euthanasia of the mice on the 60th day, the cyst area was also measured after autopsy and, the histopathological changes of the secondary cysts for each group were observed. The therapeutic efficacy of CUR-NE in infected groups was evaluated by two methods: CT scan and autopsied cyst measurements. RESULTS: Septal calcification in three groups of infected mice (CEI1, CEI2, and CEI4) was revealed by CT scan. The therapeutic efficacy of CUR-NE 40 mg/kg/day (CEI1 group) was 24.6 ± 26.89% by CT scan measurement and 55.16 ± 32.37% by autopsied cysts measurements. The extensive destructive effects of CUR-NE 40 mg/kg/day (CEI1 group) on the wall layers of secondary CE cysts were confirmed by histopathology. CONCLUSION: The current study demonstrated a significant therapeutic effect of CUR-NE (40 mg/kg/day) on secondary CE cysts in BALB/c mice. An apparent septal calcification of several cysts revealed by CT scan and the destructive effect on CE cysts observed in histopathology are two critical key factors that suggest curcumin nanoemulsion could be a potential treatment for cystic echinococcosis.

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

Chinese patent medicine combined with calcium channel blockers in the treatment of essential hypertension:a Bayes network meta-analysis and systematic review.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis. Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger's test and represented with funnel plots. All statistical analyses were executed within the R statistical framework. Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosis.

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.