Artesunate Combined with Other Medications and Action Mechanism： A Review / 中国实验方剂学杂志

A sesquiterpene natural substance called artemisinin was discovered in Artemisia annua. One of its derivatives， artesunate （ART）， has the properties of economy， immediate effect， low toxicity， and good tolerance. Since it has a quick and powerful killing effect on plasmodium in the erythrocyte phase and can quickly handle clinical seizure and symptoms， it is currently mostly utilized to treat cerebral malaria and other severe instances of malaria. In addition， it has antitumor， antivirus， anti-hepatic fibrosis， anti-inflammatory， antibacterial， hepatocyte protection， immunological modulation， and other pharmacological properties and can inhibit cell proliferation， induce cell apoptosis， and reduce the incidence of sepsis. In many countries， artemisinin-based combination therapies （ACTs）， such as artemether-benflumetol， artesunate-amodiaquine， and artemether-lumefantrine， are the first-line treatments for malaria. Recent research on artesunate by Chinese and international scholars has revealed that compared with monotherapy， artesunate combination therapy offers more benefits in terms of improving pharmacological effects， shortening the duration of medicine， and minimizing adverse effects. Through systematic retrieval of Web of Science Core Collection and integration through CiteSpace （6.2.1） software， this article reviewed the mechanism of artesunate combined with other medications with regard to antimalarial， antitumor， antibacterial， and antiviral features in the previous five years， so as to provide some theoretical basis for rational development and utilization of ART and new drug research and development.

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

Desmopressin Plus Tolterodine vs Desmopressin Plus Indomethacin for Refractory Pediatric Enuresis: An Open-label Randomized Controlled Trial

Objective: To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children. Design: Open-label randomized controlled trial. Setting: Bandar Abbas Children’s Hospital, a tertiary care children’s hospital in Iran, from March 21, 2018, to March 21, 2019. Participants: 40 children older than five years with monosymptomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy. Intervention: Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months. Outcome: Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted. Results: After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I; mean (SD) percent in nocturnal enuresis reduction at 1 [58.86 (7.27)% vs 31.18 (3.85) %; P<0.001], 3 [69.78 (5.99)% vs 38.56 (3.31)%; P<0.000], and 5 [84.84(6.21)% vs 39.14 (3.63)%; P<0.001] months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I (50% vs 20%; P=0.047). None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms. Conclusion: Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.

Sequential analysis of erythrocyte aggregation in P. falciparum malaria with and without ASAQ therapy by optical signal and image analysis

The aggregation of erythrocytes is an important mechanism for blood flow through the cardiovascular system. In malaria, this is complicated by infection caused by P. falciparum and is further complicated by the severity of parasitemia. Hence analysis of this micro-mechanism is essential to know the changes in blood not only in diseased conditions but also after artemisinin combination therapy (ASAQ) to alleviate suffering. For analysis purposes, aggregation of erythrocytes was determined by LED laser aggregometer, represented in terms of various parameters related to the changes in laser transmitted intensity. Formed aggregates are further analyzed by imaging and image-processing methods. For this study blood samples from young adults (18 – 40 years old) infected with P. falciparum (n= 80), without any other serious illness, were performed. These samples were selected based on the severity of parasitemia, and were divided into low (LP), medium1 (MP1), medium 2 (MP2), and high (HP) parasitemia. For three days, the selected individuals were treated with artemisinin-based combination therapy ASAQ (Artesunate 4 mg/kg and amodiaquine 10 mg base/ kg once a day). Healthy subjects (n=20) without any history of the disease were selected as a control group. The results, as obtained by various parameters, show a significant elevation of aggregation of erythrocytes (P< 0.05) in P. falciparum malaria with the increase of parasitemia level. There was a decrease in the aggregation after treatment on day four tending towards normal. Thus the current study shows the potential beneficial role of ASAQ on erythrocytes aggregation, which may contribute to reducing the harmful effects on various organs in P. falciparum-infected blood.

Obtener un mejor tratamiento para el paciente con hipotiroidismo

Introducción: El hipotiroidismo es una entidad de visita frecuente al endocrinólogo, establecer el mejor tratamiento es un desafío, a pesar del manejo adecuado y de un control hormonal óptimo, en ocasiones los pacientes continúan con los síntomas que afectan su calidad de vida, por lo que el tratamiento debe ser individualizado, basado en la mejor evidencia. Objetivo: Establecer las mejores opciones terapéuticas en las diferentes formas de presentación del hipotiroidismo. Métodos: Se realizó una búsqueda bibliográfica no sistemática en las bases de datos de PubMed, Medline, LILACS, EMBASE, Redalyc y guías internacionales. Los criterios de inclusión fueron publicaciones en inglés y español, en las que el título, palabras clave o resumen incluyen información pertinente al objetivo de estudio, periodicidad no mayor a los 5 años a excepción de las guías que son las últimas revisiones. En la búsqueda se obtuvieron 30 artículos de los cuales fueron 14 seleccionados. Conclusiones: Se establecieron las opciones terapéuticas con el fin de obtener un mejor tratamiento para el paciente hipotiroideo que debe ser individualizado y basado en la mejor evidencia, para alcanzar un control adecuado de su enfermedad, mejorar la calidad de vida y evitar complicaciones relacionadas con esta patología.

Introduction: Hypothyroidism is an entity that is frequently seen at the endocrinologist´s. establishing the best treatment is a challenge, despite proper management and optimal hormonal control, sometimes patients continue with symptoms which affect their quality of life, therefore that treatment should be individualized, based on the best evidence. Objective: To establish the best therapeutic options in hypothyroidism different forms of presentation. Methods: A non-systematic bibliographic search was carried out in PubMed, Medline, LILACS, EMBASE, Redalyc databases and in the international guidelines. The inclusion criteria were publications in English and Spanish, in which the title, keywords or abstract include relevant information to the objective of the study, with a periodicity of no more than 5 years, except for the guidelines that the latest revisions were used. In the search, 30 articles were retrieved, 14 which were selected. Conclusions: The therapeutic options were established in order to find better treatment for hypothyroid patients, which must be individualized and based on the best evidence, to achieve adequate control of the disease, to improve the quality of life and to avoid related complications.

Short-term efficacy and safety analysis of TACE combined with TKI and PD-1 inhibitors in the treatment of initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in the treatment of patients with initially unresectable hepatocellular carcinoma.Methods:The clinical data of 42 patients with initially unresectable hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were included. There were 31 males and 11 females, with a median age of 56 years old (range, 45-72 years old). All patients received TACE+ TKI+ PD-1 inhibitor combined treatment. The systemic treatment cycles were calculated by the regimen of immunotherapy. The timing of local treatment depends on tumor size, blood supply and treatment response. Patients were followed up through hospitalization, outpatient visits and telephone review. The Kaplan-Meier curves were obtained for survival analysis.Results:The dosing cycle to achieve optimal imaging response in the patients was 4 (3, 7) [ M( Q1, Q3)], with a systemic treatment time of 141 (65, 194) d [ M( Q1, Q3)] and 2 (1, 3) times [ M( Q1, Q3)] of local treatments. All patients were evaluated by modified response evaluation criteria in solid tumors criteria after treatment, including nine patients with complete response (CR), 21 with partial response, eight with stable disease, and four with progressive disease. Objective response rate and disease control rate were 71.4% (30/42) and 90.5% (38/42), respectively. Treatment-related adverse reactions occurred in 85.7% (36/42) of patients and grade Ⅲ or Ⅳ adverse reactions occurred in 16.7% (7/42). There was no level Ⅳ adverse reactions. All adverse reactions were controlled after dose reduction and symptomatic treatment. Thirteen patients (31.0%, 13/42) redeemed resectable after treatment and underwent radical surgery. Seven patients had pathological CR after surgery. In two patients, the pathological residual cancer tissue was less than 10%. The cumulative overall survival rates of the 42 patients at 6 months, 1 year, 1.5 years after treatment were 100%, 91.7%, and 65.0%, respectively. The postoperative 1-year survival rate of patients undergoing surgery after successful conversion was 83.3%. Conclusion:This study preliminarily showed the safety and efficacy of TACE, TKI, and PD-1 inhibitor combined therapy in patients with initially unresectable hepatocellular carcinoma.

Hot topics in perioperative immune combination therapy for liver cancer / 中华肝胆外科杂志

Most patients with primary hepatocellular carcinoma (HCC) are already in advanced stage when they are diagnosed, with a short survival period and an extremely poor prognosis. HCC seriously threatens the life and health of Chinese people. In recent years, breakthroughs have been made in systemic treatment of HCC, especially in immunotherapy represented by immune checkpoint inhibitors, which has broken the single therapy situation of molecular targeted drugs. And the strategy of immunotherapy combined with anti-angiogenic therapy has shown superiority and profoundly changed the treatment strategy of HCC. This article focuses on several hotspots of immune checkpoint inhibitors combined with anti-angiogenic targeted drugs in the perioperative scenario of HCC, and takes stock of the latest research progress of immunotherapy combined with anti-angiogenic drugs regimens in the perioperative application of HCC.

Advances and the status of radiotherapy in advanced esophageal cancer / 中华放射肿瘤学杂志

Radiotherapy plays an important role in the treatment of advanced esophageal cancer. Under the premise of effective systemic treatment, selecting patients who may benefit from local radiotherapy can effectively relieve symptoms and improve quality of life, and it is expected to prolong the survival time of patients. Moreover, immunotherapy plays an increasingly significant role in advanced esophageal cancer, and the efficacy of radiotherapy combined with immunotherapy is promising.

Research progress on tumor treating fields combined with radiation therapy in the treatment of glioblastoma / 中华放射肿瘤学杂志

For patients with newly diagnosed glioblastoma, tumor treating fields (TTF) combined with temozolomide after radiation therapy is currently one of the standard therapeutic regimens. Recently, TTF has been increasingly applied in combination with radiation therapy since it can delay tumor DNA repair and increase DNA replication stress. The efficacy of TTF has been proven in clinical studies. However, no consensus has been reached regarding the theoretical basis, radiation dose, actual clinical operation, patients' benefit and safety, which remain controversial. In this article, research progress on these topics was reviewed.

Review of advances in chemotherapy for thyroid cancer / 中华内分泌外科杂志

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Advances in Molecular Targeted Drugs for Hepatocellular Carcinoma / 中山大学学报(医学科学版)

Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.

Effects of acute-phase monotherapy and combination therapy on quality of life in patients with depressive disorders / 四川精神卫生

BackgroundThe treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values， quality of life is thus of relatively high evaluative value. In China， there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder. ObjectiveTo explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase， so as to provide references for optimizing the outcome of treatment for such patients. MethodsA prospective follow-up cohort study from August 24， 2020 to November 29， 2021 was conducted， including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes， recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into monotherapy group （n=969） and combination therapy group （n=361） according to the acute phase treatment protocol. At baseline， the end of the first half month as well as the 1st， 2nd， 3rd， 6th， 9th and 12th months of treatment， patients were assessed with Inventory of Depressive Symptomatology Self-report （IDS-SR30）， Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form （Q-LES-Q-SF）， Concise Health Risk Tracking Scale （CHRT） and Siehan Disability Scale （SDS）. Frequency， Intensity， and Burden of Side Effects Rating （FIBSER） was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk， adverse reactions and impaired social functioning among patients. ResultsAt the end of three months of treatment， the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group， and the difference was statistically significant （Z=2.008， P<0.05）. The time effects of both treatment protocols possessed statistical significance （F=111.393， P<0.01）. At the end of three months of treatment， the Q-LES-Q-SF score was negatively correlated with CHRT and SDS scores， respectively， in both monotherapy group and combination treatment group （r=-0.660， -0.712， -0.634， -0.718， P<0.01）. ConclusionBoth monotherapy and combination therapy can facilitate the improvement of the life quality of patients with acute depressive disorder， but monotherapy may achieve better than the combination therapy in this aspect. ［Funded by The National Key Research and Development Program of China "Research on the Prevention and Control of Major Chronic Non-communicable Diseases" （number， 2017YFC1311101）］

Correlation Between ERK1/2 Signal Transduction and Ovarian Cancer / 肿瘤防治研究

Ovarian cancer is one of the common tumors in female reproductive organs and accounts for about 4% of all malignant tumors in women. It is also the leading cause of death among various gynecological tumors. Surgery combined with chemotherapy is the frequently used treatment for ovarian. Chemotherapy resistance is one of the main reasons for the recurrence and poor prognosis of ovarian cancer. Various components of the MAPK pathway, also known as the RAS-RAF-MEK-ERK signaling cascade, are related to cancer, and ERK1/2 is an indispensable key site in this pathway. Continuous research has found that ERK1/2 is a "ferryman" involved in regulating the occurrence, development, and drug resistance mechanisms of ovarian cancer. This article briefly introduces the activation mechanism and pathway of the ERK1/2 signaling pathway, summarizes its relationship to ovarian cancer, and emphasizes that ERK1/2 inhibitors may be a new treatment strategy with potential advantages in improving poor prognosis in patients with ovarian cancer.

Research progress on drug combination therapy against Candida albicans / 药学实践杂志

Candida albicans is one of the most common species of Candida, which is an important cause of invasive candidiasis in clinic. Due to the frequently use of classical antifungal agents, there are amounts of drug resistant C. albicans being isolated, causing the significantly decreasing of the efficacy of some antifungal agents in clinical treatment. Besides, the use of some compounds in clinic has been limited because of their toxicities. In such a context, drug combination therapy shows great potential on antifungal because of the synergy of different drugs or therapeutic methods that could bring, which could improve the weaknesses of single drug.

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Synergistic activation of AMPK by AdipoR1/2 agonist and inhibitor of EDPs-EBP interaction recover NAFLD through enhancing mitochondrial function in mice

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

In vitro bacteriostatic and serum pharmacological tests of Qiguiyin decoction combined with levofloxacin against pseudomonas aeruginosa / 中国药理学通报

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI

Single - nucleotide polymorphisms of artemisinin resistance - related Pfubp1 and Pfap2mu genes in Bioko Island, Equatorial Guinea from 2018 to 2020 / 中国血吸虫病防治杂志

Objective To investigate the prevalence of single nucleotide polymorphisms (SNPs) of artemisinin resistance-related Pfubp1 and Pfap2mu genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea, so as to to provide baseline data for the formulation of malaria control strategies in Bioko Island. Methods A total of 184 clinical blood samples were collected from patients with P. falciparum malaria in Bioko Island, Equatorial Guinea from 2018 to 2020, and genomic DNA was extracted. The Pfubp1 and Pfap2mu gene SNPs of P. falciparum were determined using a nested PCR assay and Sanger sequencing, and the gene sequences were aligned. Results There were 159 wild-type P. falciparum isolates (88.83%) from Bioko Island, Equatorial Guinea, and 6 SNPs were identified in 20 Pfubp1-mutant P. falciparum isolates (11.17%), in which 4 non-synonymous mutations were detected, including E1516G, K1520E, D1525E, E1528D. There was only one Pfubp1gene mutation site in 19 Pfubp1-mutant P. falciparum isolates (95.00%), in which non-synonymous mutations accounted for 68.42% (13/19). D1525E and E1528D were identified as major known epidemic mutation sites in the Pfubp1 gene associated with resistance to artemisinin-based combination therapies (ACTs). At amino acid position 1525, there were 178 wild-type P. falciparum isolates (99.44%) and 1 mutant isolate (0.56%), with such a mutation site identified in blood samples in 2018, and at amino acid position 1528, there were 167 wild-type P. falciparum isolates (93.30%) and 12 mutant isolates (6.70%). The proportions of wild-type P. falciparum isolates were 95.72% (134/140), 79.25% (126/159) and 95.83% (161/168) in the target amplification fragments of the three regions in the Pfap2mu gene (Pfap2mu-inner1, Pfap2mu-inner2, Pfap2mu-inner3), respectively. There were 16 different SNPs identified in all successfully sequenced P. falciparum isolates, in which 7 non-synonymous mutations were detected, including S160N, K199T, A475V, S508G, I511M, L595F, and Y603H. There were 7 out of 43 Pfap2mu-mutant P. falciparum isolates (16.28%) that harbored only one gene mutation site, in which non-synonymous mutations accounted for 28.57% (2/7). For the known delayed clearance locus S160N associated with ACTs, there were 143 wild-type (89.94%) and 16 Pfap2mu-mutant P. falciparum isolates (10.06%). Conclusions Both Pfubp1 and Pfap2mu gene mutations were detected in P. falciparum isolates from Bioko Island, Equatorial Guinea from 2018 to 2020, with a low prevalence rate of Pfubp1 gene mutation and a high prevalence rate of Pfap2mu gene mutation. In addition, new mutation sites were identified in the Pfubp1 (E1504E and K1520E) and Pfap2mu genes (A475V and S508G).

Macrophage-camouflaged epigenetic nanoinducers enhance chemoimmunotherapy in triple negative breast cancer

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.