Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.

Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

The effect of bladder function on the efficacy of transurethral prostatectomy in patients with benign prostatic hyperplasia: a retrospective, single-center study.

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

Using Whale Optimization Algorithm and Haze Level Information in a Model-Based Image Dehazing Algorithm.

Single image dehazing has been a challenge in the field of image restoration and computer vision. Many model-based and non-model-based dehazing methods have been reported. This study focuses on a model-based algorithm. A popular model-based method is dark channel prior (DCP) which has attracted a lot of attention because of its simplicity and effectiveness. In DCP-based methods, the model parameters should be appropriately estimated for better performance. Previously, we found that appropriate scaling factors of model parameters helped dehazing performance and proposed an improved DCP (IDCP) method that uses heuristic scaling factors for the model parameters (atmospheric light and initial transmittance). With the IDCP, this paper presents an approach to find optimal scaling factors using the whale optimization algorithm (WOA) and haze level information. The WOA uses ground truth images as a reference in a fitness function to search the optimal scaling factors in the IDCP. The IDCP with the WOA was termed IDCP/WOA. It was observed that the performance of IDCP/WOA was significantly affected by hazy ground truth images. Thus, according to the haze level information, a hazy image discriminator was developed to exclude hazy ground truth images from the dataset used in the IDCP/WOA. To avoid using ground truth images in the application stage, hazy image clustering was presented to group hazy images and their corresponding optimal scaling factors obtained by the IDCP/WOA. Then, the average scaling factors for each haze level were found. The resulting dehazing algorithm was called optimized IDCP (OIDCP). Three datasets commonly used in the image dehazing field, the RESIDE, O-HAZE, and KeDeMa datasets, were used to justify the proposed OIDCP. Then a comparison was made between the OIDCP and five recent haze removal methods. On the RESIDE dataset, the OIDCP achieved a PSNR of 26.23 dB, which was better than IDCP by 0.81 dB, DCP by 8.03 dB, RRO by 5.28, AOD by 5.6 dB, and GCAN by 1.27 dB. On the O-HAZE dataset, the OIDCP had a PSNR of 19.53 dB, which was better than IDCP by 0.06 dB, DCP by 4.39 dB, RRO by 0.97 dB, AOD by 1.41 dB, and GCAN by 0.34 dB. On the KeDeMa dataset, the OIDCP obtained the best overall performance and gave dehazed images with stable visual quality. This suggests that the results of this study may benefit model-based dehazing algorithms.

[Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics].

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

Adult primary testicular lymphoma: clinical features and survival in a series of patients treated at a high-volume institution in China.

BACKGROUND: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute. METHODS: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters. RESULTS: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients. CONCLUSION: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Association Between the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A Polymorphisms and Atopic Dermatitis Susceptibility: A Meta-Analysis.

Aims: The aim of this study was to summarize the currently available evidence on the associations between the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and susceptibility to atopic dermatitis (AD). Materials and Methods: Five electronic databases including PubMed, the Web of Science, Excerpta Medica dataBASE, the Cochrane Library, and the China National Knowledge Infrastructure were searched for potential studies. Studies illustrating the association of the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and AD susceptibility were included in this meta-analysis. For a study to be included, it had to have been published before September 20, 2018. Study quality was assessed using the Newcastle-Ottawa scale. Summary odds ratios and 95% confidence intervals were calculated to evaluate potential associations under five genetic models. Results: A total of 15 case-control studies comprising of 1647 AD patients and 2031 controls were included in this meta-analysis. Their methodological qualities were generally high. We confirmed an association between the IL-10-819G/A polymorphism and AD, but there was an insignificant association identified between the IL-10-1082G/A and the IL-10-592A/C polymorphisms and AD when all ethnic groups were considered together. The subgroup analyses revealed some ethnic-specific effects. For the IL-10-819G/A polymorphism, individuals with the GG-genotype seemed to have an increased risk of AD among Caucasian populations, but less so in the Asian populations. However, for the IL-10-1082G/A polymorphism, the GG-genotype carriers seemed to be more susceptible to AD in the Asian populations than in the Caucasian populations. Conclusions: This meta-analysis suggests that the IL-10-819G/A polymorphism seems to be associated with increased risk of AD among Caucasian populations, and that the IL-10-1082G/A polymorphism seems to be correlated with AD among Asian populations.

[ARV-7: A biomarker for the treatment of metastatic castration-resistant prostate cancer].

As more and more patients with metastatic prostate cancer develop resistance to androgen-deprivation therapy (ADT) and consequently castration-resistant prostate cancer (CRPC), reasonable selection of therapies is becoming increasingly important for the prediction of the therapeutic results. Many studies show that androgen receptor splice variant 7 (AR-V7) is involved in the development and progression of CRPC and that the expression of AR-V7, absolutely higher in CRPC than in hormone-nave prostate cancer, plays a significant role in the mechanisms of resistance to abiraterone, enzalutamide and taxane chemotherapies. Further more, some clinical trials have revealed that the AR-V7 level may indicate the prognosis of different therapeutic options: AR-V7 negative in circulating tumor cells suggesting the effectiveness of a new hormonal therapy and taxane chemotherapy while AR-V7 positive indicating the poor result of a new hormonal therapy. These findings show that AR-V7 could be a biomarker for therapeutic options and the prognostic evaluation of CRPC.

Effect of Ce Addition on Modifying the Microstructure and Achieving a High Elongation with a Relatively High Strength of As-Extruded AZ80 Magnesium Alloy.

Forming magnesium alloys with rare earth elements (La, Gd, Nd, Y, Ce) is a routine method for modifying their microstructure and properties. In the present work, the effect of Ce addition on the microstructure evolution and the mechanical properties of as-extruded Mg-8Al-0.5Zn (AZ80) alloy was investigated. All of the extruded AZ80-xCe (x = 0, 0.2, 0.8 and 1.4 wt %) alloys exhibited equiaxed grains formed by fully dynamic recrystallization, and the grain size of the extruded AZ80 alloy was remarkably reduced by ~56.7% with the addition of 1.4 wt % Ce. Furthermore, the bulk-shaped Al4Ce phase formed when Ce was first added, with the Ce content rising to 0.8 wt % or higher, and Al4Ce particles in both the nano- and micron sizees were well distributed in the primary α-Mg matrix. The area fraction of the Al4Ce particles expanded with increasing Ce content, providing more nuclei for dynamic recrystallization, which could contribute to the grain refinement. The results of the tensile tests in this study showed that Ce addition effectively improved the room temperature formability of the as-extruded AZ80 alloy, without sacrificing strength. The significantly improved mechanical properties were ascribed to excellent grain refinement, weakened texture strength, an increased Schmid factor, and a reduced area fraction of low-angle grain boundaries, all resulting from Ce addition to the as-extruded AZ80 alloy. The contribution of the nano-Al4Ce precipitates on improving the mechanical properties was also discussed in this paper.

[Preparation of new protein carrier of vaccine against pneumococcal otitis media with genetic engineering technology].

OBJECTIVE: To prepare pneumolysin as a new protein carrier of vaccine against otitis media with genetic engineering technology and establish the base of the study on pneumococcal conjugative vaccines. METHODS: Genomic DNA was isolated from streptococcus pneumoniae. A pair of primers which included two restriction sites was designed based on the published pneumolysin gene sequence. The pneumolysin gene was amplified from pneumococcal DNA with PCR technology. The restriction enzyme digested fragment was linked into the cloning vector PET-28a and the recombinant plasmid DNA containing pneumolysin was then transfected into host cell E. coli JM109 (DE3). RESULTS: DNA fragments were subcloned to construct the complete pneumolysin gene by a conventional coning and PCR. The inserted pneumolysin gene sequence was confirmed by DNA sequencing and the pneumolysin protein was successfully expressed. The relative molecular mass of the expressed product was 52 000. The expressed product amounted to 8% of the total host cell protein. CONCLUSIONS: The pneumolysin gene was successfully cloned into host cell using genetic engineering technology. The recombinant pneumolysin was expressed and purified for preparation. This work laid a foundation of the preparation of pneumococcal conjugative vaccines.

[Diagnosis and management of facial nerve neuromas].

OBJECTIVE: To provide the experience for early diagnosis and management of facial nerve neuromas, and to discuss the clinic and imaging feature of facial nerve schwannoma and facial nerve fibroma in 22 cases. METHODS: Twenty cases facial nerve schwannoma and two cases of facial nerve neurofibroma were diagnosed and reviewed retrospectively. Surgical removal were performed through the middle cranial fossa in 2 cases, through intratemporal approach in 8 cases, through intraparotid approach in 2 cases, and combined intra-temporal with out-temporal approaches in 10 cases. Seventeen cases underwent facial nerve graft for repairing a facial nerve defect. Great auricular nerve was used in 3 cases with intratemporal approach and 1 case with intratemporal combined intraparotid approach. Sural nerve graft was used in 5 cases with intratemporal approach and 8 cases with intra-temporal combined intraparotid approach. Two cases were employed two-stage facial muscle flap-plasty. RESULTS: Facial nerve neuromas were totally removed in 21 cases and subtotal neuroma removed in 1 case. In these cases, 20 patients were no recurrence and 1 patient was lost follow-up. One patient with subtotal neuroma removal received Gamma Knife treatment before and after surgery, and this case was no recurrence. The CT imaging of the temporal bone showed that schwannoma was separated "white mass" with smooth margin along the region of facial nerve without intact canal. But neurofibroma locate in enlarge fallopian with intact canal. Magnetic resonance imaging had the advantage of evaluating all segments of the facial nerve and showed continuity of intratemporal and intraparotid mass with the facial nerve. Pathological results indicated that 20 cases were diagnosed as facial nerve schwannoma and 2 cases were neurofibroma. CONCLUSIONS: Although tumors originating from the facial nerve are extremely rare, it is possible to make early diagnosis through finding clinical feature and imaging methods. Generally, systematic surgical approach for tumor removal and facial nerve reconstruction should be considered in the cases with facial neurinoma.