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2.
BMC Womens Health ; 24(1): 352, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890676

ABSTRACT

PURPOSE: The aim of this study was to describe the longitudinal developmental trajectories and its influencing factors of sexual activity in patients with breast cancer during treatment. METHODS: A prospective longitudinal study was conducted, including 225 newly diagnosed breast cancer patients in A tumor specialty three-class hospital in Southwest China. We measured sexual activity at the time of admission and diagnosis (T0) and one month (T1), three months (T2), six months (T3), and nine months (T4) after diagnosis. A trajectory analysis model (GBTM) was used to explore the changes in sexual activity in breast cancer patients. Multivariate binary logistic regression analysis was used to analyse the factors that affected the classification of sexual activity trajectories. RESULTS: The ratio of sexual activity abruptly declined from 100% at baseline to 39.1% at T1. The percentage of sexual activity was improved, from 51.4% at T2 to 63.1% at T4. The optimal model was a 2-group trajectory of sexual activity in breast cancer patients,36.6% in the "low activity group" and 63.4% in the "high activity group." The multivariate binary logistic regression analysis revealed statistically significant and positive correlations between sexual activity and age (ß = 0.085, OR = 1.089, 95%CI 1.035 ∼ 1.145, P = 0.001),libido(ß = 0.774, OR = 2.168, 95%CI 1.337 ∼ 3.515, P = 0.002), vaginal lubrication(ß = 1.254, OR = 33.503, 95%CI 2.000 ∼ 6.137, P<0.001). CONCLUSIONS: Breast cancer patients exhibited varying levels of sexual activity during treatment; higher age was associated with increased sexual activity, which can contribute to the recovery of sexual function. Therefore, it is crucial to provide appropriate guidance on sexual health for younger patients.


Subject(s)
Breast Neoplasms , Sexual Behavior , Humans , Female , Breast Neoplasms/therapy , Longitudinal Studies , China/epidemiology , Middle Aged , Sexual Behavior/psychology , Adult , Prospective Studies , Aged , Age Factors
3.
Zool Res ; 45(4): 747-766, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38894519

ABSTRACT

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.


Subject(s)
COVID-19 , Disease Models, Animal , Pandemics , SARS-CoV-2 , Animals , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Humans , Mice , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pneumonia, Viral/therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus Infections/therapy , Betacoronavirus/immunology , Cricetinae
4.
J Org Chem ; 89(14): 10004-10011, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38935867

ABSTRACT

N-Alkoxyphthalimides, one kind of phthalimide derivative, have great importance in synthesis, mainly used as free radical precursors. While the phthalimide unit, for a long time, was treated as part of the waste stream. Construction of C-N bonds has always been a hot spot, especially in reductive cross-coupling. Herein, a nickel-catalyzed reductive cross-coupling reaction of N-methoxyphthalimides with alkyl halides is described, where N-methoxyphthalimides serve as nitrogen electrophiles. This tactic provides a new approach to construct C-N bonds under mild neutral conditions. Alkyl chlorides, bromides, iodides, and sulfonates are all fit to this transformation. Moreover, the reaction could tolerate a broad substrate scope, especially base-sensitive functional groups (boron or silicon groups), as well as competitive nucleophilic groups (phenols and amides), which are incompatible with traditional Gabriel synthesis under basic conditions, demonstrating a complementary role of this work to Gabriel synthesis.

5.
AIDS Res Hum Retroviruses ; 40(9): 521-530, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38535626

ABSTRACT

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.


Subject(s)
Anti-Retroviral Agents , Macaca mulatta , RNA, Viral , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus , Viral Load , Animals , Simian Acquired Immunodeficiency Syndrome/virology , Simian Acquired Immunodeficiency Syndrome/drug therapy , Simian Immunodeficiency Virus/genetics , Simian Immunodeficiency Virus/isolation & purification , Anti-Retroviral Agents/therapeutic use , DNA, Viral , Viremia/virology , Viremia/drug therapy , Virus Latency , Disease Reservoirs/virology , Virus Replication
6.
Front Pharmacol ; 15: 1298409, 2024.
Article in English | MEDLINE | ID: mdl-38375038

ABSTRACT

Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE). Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation. Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group. Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863.

7.
Natl Sci Rev ; 11(2): nwad324, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38314400

ABSTRACT

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively, and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.

8.
Adv Sci (Weinh) ; 11(9): e2306923, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38088530

ABSTRACT

Transition metal-catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late-stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel-catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross-electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late-stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process.

9.
Chinese Journal of School Health ; (12): 503-508, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016869

ABSTRACT

Objective@#To analyse associated factors of campus bullying in schools, and to construct a nomogram model to predict the risk of campus bullying, so as to provide a theoretical basis for campus bullying prevention and control.@*Methods@#In September 2023, 89 117 middle and high school students were selected by stratified cluster random sampling method within 12 cities (103 counties) in Inner Mongolia, and were surveyed with self administered questionnaire. Among them, there were 62 381 participants in the training set and 26 736 participants in the testing set. Statistical analysis was conducted using χ 2 test and multiple Logistic regression, and a nomogram model was drawn for predicting campus bullying.@*Results@#The prevalence of campus bullying was 3.49%. Living in a suburban county, living in an unstable family, not the only child, having a father with a college degree or above, sometimes or never eating breakfast, being overweight or obese, living on campus, being scolded by parents in the past 30 days, smoking, Internet addiction, experiencing depression, anxiety symptoms, recreational soluble solvents use, cough medicine abuse, nonprescribed use of sedatives were all positively correlated with campus bullying ( OR =1.18, 1.40, 1.12, 1.33, 1.13, 1.72 , 1.12, 1.17, 1.82, 1.32, 1.83, 3.92, 2.40, 2.25, 1.51, 1.63, P <0.01).There were a negative correlation between high school students, female students, and the number of physical education classes per week (2-3, ≥4) with campus bullying ( OR =0.67, 0.58, 0.72, 0.83, P <0.01). The prediction model of campus bullying risk was established by nomogram model. The area under curve (AUC) was 0.82, and the calibration curve showed that the predicted value was close to the actual value.@*Conclusions@#Bullying among middle and high school students are related to family intimacy, poor daily behaviour and psychological factors. Targets of bullying intervention in schools should be identified, and preventive and control measures against bullying in secondary schools should be formulated, so as to reduce the occurrence of campus bullying.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1018699

ABSTRACT

Objective To analyze the relationship between MyD88L265P and CD79B mutations in tumor tissue and the prognosis of primary central nervous system lymphoma(PCNSL).Methods 18 PCNSL patients with normal immune function(no history of HIV infection and immunosuppressants administration)who were diagnosed by craniotomy or stereotaxic biopsy in the Second Hospital of Lanzhou University from August 2018 to November 2020 were retrospectively analyzed.Real-time quantitative PCR and first-generation sequencing techniques were respectively used to detect MyD88L265P and CD79B mutations in tumor tissues of 18 PCNSL patients.Univariate analysis and Cox regression multivariate analysis were performed for indicators that may be associated with first progression-free survival(PFS)and overall survival in PCNSL.Results The mutation rate of MyD88L265P was 38.9%,the mutation rate of CD79B was 33.3%,and the co-mutation rate of MyD88L265P/CD79B was 27.8%in PCNSL tissue of 18 patients.Univariate analysis showed that the PCNSL patients with multiple lesions,deep involvement of lesions,and tissue CD79B mutation had a statistically significant shorter time of PFS(P<0.05).Multivariate analysis showed that deep lesion involvement(HR=0.135,95%CI 0.023-0.799,P<0.05)and CD79B mutation(HR=0.149,95%CI 0.028-0.800,P<0.05)in PCNSL tissue were independent prognostic factors for PCNSL patients.Conclusion The frequency of MyD88L265P and CD79B mutations was high in tumor tissues of 18 PCNSL patients,and these two gene mutations may be associated with poor prognosis of PCNSL,especially CD79B mutation.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1021443

ABSTRACT

BACKGROUND:Subepithelial connective tissue grafts are generally considered as the gold standard for soft tissue augmentation.However,it needs a second surgical site,which will prolong the surgical time and increase patients'pain. OBJECTIVE:To compare the histological and thickness changes of attached gingiva following grafting with different soft tissue substitutes in the labial region of the cuspids. METHODS:In three Beagle dogs,attached gingival augmentation was performed with double-layer allogeneic acellular dermal matrix membrane(AADM),bovine-derived acellular dermal matrices(BADM)combined with concentrated growth factor membrane or BADM combined with collagen sponge.Thickness of attached gingiva was measured before augmentation,and 1,2,3,and 4 months after augmentation.Histological analyses were performed after 4 months. RESULTS AND CONCLUSION:The mean values of attached gingival thickness and attached gingival thickness augmentation were higher in the double-layer AADM group than in the other two groups(all P<0.05)from the 1st to 4th month after surgery.At 1 month after surgery,the attached gingival thickness of the three groups increased significantly and then decreased.At 3 months after surgery,the BADM combined with collagen sponge group and the BADM combined with concentrated growth factor membrane group showed no significant difference in the attached gingival thickness of the graft area compared with that before surgery(P>0.05).At 4 months after surgery,the mean value of attached gingival thickness in the double-layer AADM group was still significantly increased compared with that before surgery(P<0.05).The value of attached gingival thickness was highest in the double-layer AADM group,followed by the BADM combined with collagen sponge group,and the lowest in the BADM combined with concentrated growth factor membrane group at 1-4 months after surgery.Histological analyses revealed that AADM was well integrated with the host gingival tissue,and new fibrous connective tissue and fibroblasts grew into the AADM.But the grafts in the other two groups were absorbed and the augmentation area was remodeled into a structure consistent with the surrounding host tissue.To conclude,AADM is superior to BADM combined with concentrated growth factor and BADM combined with collagen sponge with regard to gingival augmentation.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1031583

ABSTRACT

【Objective】 To investigate the mechanism of C-C motif chemokine ligand 5 (CCL5) modulation by extracellular matrix stiffness in non-small cell lung cancer (NSCLC) and to determine the effect of CCL5 on the immunotherapy response of NSCLC. 【Methods】 The correlation between extracellular matrix stiffness and CCL5 expression in NSCLC was analyzed with the TCGA database. Polyacrylamide hydrogels with different stiffness were designed according to the extracellular matrix stiffness of NSCLC, and H1299 cells responding to the mechanical loading of hydrogel matrix stiffness were subjected to transcriptome sequencing. High matrix stiffness was verified to promote the expression of CCL5 by using sequence. 【Results】 High extracellular matrix stiffness upregulated CCL5 expression, and interferon-γ mediated signaling pathway might be involved in the process. NSCLC patients with high CCL5 expression had a greater abundance of cytotoxic T-cells in tumor tissue and reacted favorably to anti-programmed cell death protein 1 treatment. 【Conclusion】 Increased extracellular matrix stiffness promotes CCL5 synthesis, and CCL5 enhances immunotherapy responsiveness in NSCLC by increasing cytotoxic T cell infiltration in tumor tissue.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005248

ABSTRACT

In the quality control of Chinese medicine, the detection of active components and toxic and harmful components are two important links. Although conventional methods such as high performance liquid chromatography and liquid chromatography-mass spectrometry can accurately quantify the above substances, they have shortcomings such as complicated operation, high costs, inability of detection at any time, difficult detection of insoluble and macromolecular substances. Enzyme-linked immunosorbent assay (ELISA) can adsorb antigens or antibodies on the surface of solid carriers and realize qualitative or quantitative analysis of targets by using the specific reactions of antigens and antibodies. This method is praised for the simple operation, high sensitivity, strong specificity, simple requirements for experimental equipment, a wide application range, and low costs. In recent years, ELISA has been widely used in the quality control of Chinese medicine, especially in the content determination of mycotoxins represented by aflatoxin and the qualitative and quantitative analysis of active components. ELISA plays an increasingly important role with its unique advantages, providing new methods and ideas for the rapid quality examination of large quantities of Chinese medicines. This paper reviews the research progress in ELISA for the quality control of Chinese medicine in recent years and prospects its technical development and application prospects, aiming to provide reference and research ideas for further using this method to ensure the quality, safety, and controllability of Chinese medicine.

14.
China Pharmacy ; (12): 601-606, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012580

ABSTRACT

OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol, thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed, Embase, Cochrane Library, CBM, CNKI, and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria, thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them, 4 studies provided the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) (ΔSBP and ΔDBP); 4 involving the change (ΔLVEF) of left ventricular ejection fraction (LVEF). Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group (AA) and mutation group (AG+GG) of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD=0.17,95%CI (-0.97,1.31), P=0.77], ΔDBP [SMD=-0.01,95%CI (-0.65,0.62), P=0.97]}; there was no statistical significance in the improvement of ΔLVEF [SMD=-0.61, 95%CI (-2.74,1.53), P=0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP, DBP, and LVEF in cardiovascular patients who use bisoprolol.

15.
China Pharmacy ; (12): 750-757, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013114

ABSTRACT

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists and dexamethasone (referred to as “triple therapy”) in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed, Embase, the Cochrane Library, CNKI and Wanfang data, randomized controlled trials (RCTs) about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone (referred to as “dual therapy”) were collected during the inception to May 2023. After literature screening, data extraction and literature evaluation, network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included, involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone (FPD) was most effective in terms of acute nausea and vomiting control rate, followed by fosaprepitant + granisetron + dexamethasone (FGD) and aprepitant + ramosetron + dexamethasone (AMD). In terms of acute nausea control rate, FPD was the most effective, followed by aprepitant + palonosetron + dexamethasone (APD) and FGD. In terms of acute vomiting control rate, FPD was the most effective, followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

16.
Chem Commun (Camb) ; 59(97): 14439-14442, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37982295

ABSTRACT

Manganese is a cheap and environmentally friendly metal on Earth. Herein, we report a manganese-promoted reductive cross-coupling using easily available and odorless disulfides as thiolating agents in an excellent 100% sulfur atom economy. The protocol featured a broad substrate scope, including various alkyl disulfides and excellent functional group compatibility, constructing diverse thioethers under simple conditions. Ultimately, thioethers can be prepared in gram-scale reactions and further transformed into structurally complex molecules.

17.
Chem Rev ; 123(22): 12313-12370, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37942891

ABSTRACT

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of the synthesis of natural products, drugs, and complex compounds. It is anticipated that late-stage functionalization would improve drug discovery's effectiveness and efficiency and hasten the creation of various chemical libraries. Consequently, late-stage functionalization of natural products is a productive technique to produce natural product derivatives, which significantly impacts chemical biology and drug development. Carbon-carbon bonds make up the fundamental framework of organic molecules. Compared with the carbon-carbon bond construction, the carbon-carbon bond activation can directly enable molecular editing (deletion, insertion, or modification of atoms or groups of atoms) and provide a more efficient and accurate synthetic strategy. However, the efficient and selective activation of unstrained carbon-carbon bonds is still one of the most challenging projects in organic synthesis. This review encompasses the strategies employed in recent years for carbon-carbon bond cleavage by explicitly focusing on their applicability in late-stage functionalization. This review expands the current discourse on carbon-carbon bond cleavage in late-stage functionalization reactions by providing a comprehensive overview of the selective cleavage of various types of carbon-carbon bonds. This includes C-C(sp), C-C(sp2), and C-C(sp3) single bonds; carbon-carbon double bonds; and carbon-carbon triple bonds, with a focus on catalysis by transition metals or organocatalysts. Additionally, specific topics, such as ring-opening processes involving carbon-carbon bond cleavage in three-, four-, five-, and six-membered rings, are discussed, and exemplar applications of these techniques are showcased in the context of complex bioactive molecules or drug discovery. This review aims to shed light on recent advancements in the field and propose potential avenues for future research in the realm of late-stage carbon-carbon bond functionalization.

18.
Signal Transduct Target Ther ; 8(1): 169, 2023 04 24.
Article in English | MEDLINE | ID: mdl-37095086

ABSTRACT

Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 µM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 µM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.


Subject(s)
COVID-19 , HIV Infections , Pregnancy , Animals , Female , Humans , SARS-CoV-2 , Nelfinavir/pharmacology , Macaca mulatta , Prospective Studies , China , Antiviral Agents/pharmacology
19.
Ren Fail ; 45(1): 2195012, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37013479

ABSTRACT

IgA nephropathy (IgAN), an immune-mediated chronic inflammatory kidney disease, is the most common primary glomerular disease in Asia, especially in China and Japan. The pathogenesis of IgAN is complex, and the main cause of IgAN is explained by the 'multiple hit' theory, which states that the deposition of immune complexes in renal mesangial cells induces chronic inflammation that leads to kidney damage. Chronic inflammation is associated with iron metabolism, which also plays an essential role in the pathogenesis, progression, diagnosis and prognosis of IgAN. Overall, this review aimed to explore the application of iron metabolism in IgAN by systematically elaborating the relationship between iron metabolism and chronic inflammation in IgAN to speculate on the possible diagnostic and therapeutic significance of iron metabolism indicators in IgAN.


Subject(s)
Glomerulonephritis, IGA , Renal Insufficiency, Chronic , Humans , Glomerulonephritis, IGA/pathology , Immunoglobulin A , Kidney/pathology , Renal Insufficiency, Chronic/complications , Inflammation , Iron
20.
Front Endocrinol (Lausanne) ; 14: 1037773, 2023.
Article in English | MEDLINE | ID: mdl-36843611

ABSTRACT

Background: Dyslipidemia is closely related to kidney disease. We aimed to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and prognosis of IgA nephropathy (IgAN) and build a nomogram prognostic model. Methods: 519 IgAN patients with 61 months median follow-up were enrolled and divided into two groups based on the cut-off value of baseline LDL-C (2.60 mmol/L): the high group (n=253) and the low group (n=266). Renal survival was assessed by Kaplan⁃Meier (KM) survival curve. Risk factors were identified by COX regression analysis. The area under the receiver operating characteristic (ROC) curves (AUC), concordance index (C-index), and calibration curves were applied to evaluate the nomogram model. Results: KM survival curve analysis showed that the high LDL-C group had worse renal survival than the low LDL-C group (χ2 = 8.555, p=0.003). After adjusting for confounding factors, Cox regression analysis showed the baseline LDL-C level was an independent risk factor of end-stage renal disease (ESRD) in IgAN (HR=3.135, 95% CI 1.240~7.926, p =0.016). LDL-C, segmental sclerosis, tubular atrophy/interstitial fibrosis, the prevalence of cardiovascular disease, 24-hour proteinuria were identified and entered into the nomogram models, with AUC of 0.864, 0.827, and 0.792 respectively to predict the 5-, 8-, and 10-year risk of ESRD in IgAN. The C-index of this prediction model was respectively 0.862, 0.838, and 0.800 and was well-calibrated. Conclusion: Elevated LDL-C level is a predictive factor for the prognosis of IgAN. We developed a nomogram model that can predict the risk of ESRD in IgAN by using LDL-C ≥ 2.60 mmol/L.


Subject(s)
Glomerulonephritis, IGA , Kidney Failure, Chronic , Humans , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/epidemiology , Prognosis , Cholesterol, LDL , Nomograms , Kidney Failure, Chronic/etiology
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