This paper reports a case of a patient with sleep-related painful erections treated by acupuncture combined with abdominal vibration therapy. The main symptom was repeated painful penile erections during nighttime sleep. The syndrome was differentiated as "water failing to nourish wood" and "liver qi stagnation". Acupuncture was applied at Baihui (GV20), Sishencong (EX-HN1), Guanyuan (CV4), and bilateral Neiguan (PC6), Hegu (LI4), Taichong (LR3), Taixi (KI3), Guilai (ST29), Yongquan (KI1), Yanglingquan (GB34), and Sanyinjiao (SP6). The treatment was combined with abdominal vibration therapy. Treatment was given once daily, five times per week. After the first treatment, the severity and duration of nocturnal erection pain were reduced, and sleep quality was improved. After two weeks of treatment, nocturnal erection pain persisted but became tolerable, with significantly shortened duration.
Humans ; Male ; Acupuncture Points ; Acupuncture Therapy ; Erectile Dysfunction/physiopathology* ; Penile Erection ; Sleep

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

Objective To study the causes of two Chinese families with Branchio-oto syndrome.Methods The clinical data of two families were collected,and the pathogenic genes and variants of Branchio-oto syndrome were screened and verified by whole exome sequencing and Sanger sequencing.Results Two proband patients were diagnosed with Branchio-oto syndrome.Proband 1 presented with preauricular and anterior cervical fistulas,as well as congenital severe sensorineural hearing loss.On the other hand,proband 2 displayed a preauricular fistula and an anterior cervical cyst.At the age of 5,progressive deterioration of binaural hearing was observed,leadingtothe cur-rent diagnosis of severe mixed deafness.Genetic analysis showed that proband 1 and 2 carried nonsense variants of EYA1 gene:NM_000503.6:c.1408G＞T(p.Glu470Ter),and c.889C＞T(p.Arg297Ter).According to the guide-lines of the American College of Medical Genetics and Genomics(ACMG),the above variants were rated as patho-genic variants.After reviewing the literature,the c.1408G＞T variant had not been previously reported,and the c.889C＞T is a known variant.Conclusion The variants c.1408G＞T(p.Glu470Ter)and c.889C＞T(p.Arg297Ter)of EYA1 gene are the cause of these two families with Branchio-oto syndrome.The first report of c.1408G＞T broadens the mutational spectrum of EYA1 gene and provids a clinical reference for the diagnosis of Branchio-oto syndrome.

Objective To establish an index system for assessing the quality of hospital accreditation data and determine the hierarchical weights of indices at different levels,providing a reference for enhancing the governance of such data.Methods A quality assessment system for hospital accreditation data was developed using literature analysis method and Delphi method.The analytic hierarchy process was employed to create a pairwise comparison judgment matrix to determine the weights of indices.Results An evaluation system was constructed with the following levels:"Indicator Screening Quality-Data Reporting Quality-Data Quality Control Quality-Data On-Site Verification Quality."The system includes 4 first-level indicators and 18 second-level indicators.The indicator with the highest weight among the first-level indicators was Data Reporting Quality(0.496 5),followed by Data Quality Control Quality(0.313 2).Among the second-level indicators,Timeliness(0.428 6)and Cooperation(0.428 6)had the highest weights.Conclusion The establishment of the quality evaluation system of hospital accreditation da-ta is a strategy to optimize the control of hospital accreditation data quality and is beneficial for continuous improvement of hospital accreditation data quality.

Objective To investigate the molecular epidemiology of hypervirulent Klebsiella pneumoniae(HvKp)and its independent risk factors for infection,and to provide research basis for anti-infection treat-ment.Methods A total of 519 Klebsiella pneumoniae strains were collected from Inner Mongolia Forestry General Hospital from January 2020 to December 2022.String test was used to distinguish hypermyxoid strains(HMV-Kp)and non-HMV-KP.The rmpA,rmpA2,and iutA genes were detected by common PCR agarose gel electrophoresis to screen the HvKp strains.Multilocus sequence typing analysis was performed on 60 HvKp strains and the minimum spanning tree was drawn.Multivariate Logistic regression was used to ana-lyze the risk factors of HvKp infection.Results The positive rate of HMV-Kp was 39.69％,the positive rate of HvKp was 37.19％,and HMV-Kp accounted for 76.68％of HvKp.The detection rate of HvKp in general surgery department was the highest,and the detection rate of HvKp in pus specimens was the highest.By ST typing comparison,a total of 18 types of 60 HvKp strains were detected,ST23 type was the most common type(50.00％),followed by ST86 type(8.33％).Multivariate Logistic regression analysis showed that male,liver abscess,infection or suppuration of other tissues and organs,and use of macrolide antibiotics in the past 3 months were independent risk factors for HvKp infection(P＜0.05).Conclusion There is a strong associa-tion between HvKp and HMV-Kp strains,and ST23 type is the dominant type in this study.Male,liver ab-scess,infection or suppuration of other tissues and organs,and use of macrolide antibiotics in the past 3 months are independent risk factors for HvKp infection.

ObjectiveTo evaluate the effect of transcranial direct current stimulation (tDCS) on the cognitive function and quality of life in patients with Parkinson's disease. MethodsRandomized controlled trials (RCTs) on tDCS for Parkinson's disease were searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang Data from the inception to September, 2023. Control group was administered standard Parkinson's medications or placebo, physical therapy, and cognitive rehabilitation, while treatment group received tDCS additionally. The quality of the researches was evaluated using the Cochrane Risk of Bias Tool. Data synthesis and analysis were performed using RevMan 5.4 and Stata 17.0, with heterogeneity and sensitivity analyses. ResultsEight articles were included. tDCS significantly improved the scores of Montreal Cognitive Assessment (MD = 2.00, 95%CI 1.13 to 2.87, P < 0.001). However, there was no significant difference in the scores of Parkinson's Disease Questionnaire (MD = 0.73, 95%CI -5.78 to 7.23, P = 0.830), Beck Depression Inventory-Ⅱ(MD = -0.77, 95%CI -7.14 to 5.60, P = 0.810), and Unified Parkinson Disease Rating Scale-Ⅲ (MD = 1.60, 95%CI -0.77 to 3.97, P = 0.190). ConclusiontDCS may improve cognitive function of patients with Parkinson's disease.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

  Objective  To investigate the predictive value of albumin-bilirubin (ALBI) score combined with liver function index and carcinoembryonic antigen (CEA) for liver metastasis of colorectal cancer.  Methods  We retrospectively analyzed the clinical data of patients with colorectal cancer who underwent surgical treatment in the Second Hospital & Clinical Medical Hospital, Lanzhou University from January 2016 to July 2021 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into liver metastasis group and non-liver metastasis group, and were randomly divided into modeling group and validation group by a ratio of 2∶1. The risk factors of liver metastasis in the patients with colorectal cancer were analyzed. Lasso-Logistic regression was used to construct the prediction model. Bootstrap method was used for internal verification. Receiver operating characteristic curve, calibration curve and clinical decision curve were used to evaluate the reliability of the prediction model. Finally, a nomogram was drawn to show the prediction results.  Results  A total of 195 patients who met the inclusion and exclusion criteria were enrolled, including 130 in the modeling group and 65 in the validation group. Through Lasso regression variable screening and Logistic regression analysis, the results showed that ALBI score(OR=8.062, 95% CI: 2.545-25.540), alanine transaminase (ALT) (OR=1.037, 95% CI: 1.004-1.071) and CEA (OR=1.025, 95% CI: 1.008-1.043) were independent predictors of liver metastasis in colorectal cancer. The area under curve (AUC) of the combined prediction of liver metastasis of colorectal cancer in the modeling group was 0.921, the sensitivity was 78%, the specificity was 95%, the C-index was 0.921, the H-L fitting curve χ²=0.851, P=0.654, and the slope of the calibration curve was close to 1, suggesting that the accuracy of the model was high, and the DCA curve showed that the model had good clinical application value. For the data of the modeling group, the Bootstrap method was used for internal verification of 1000 resamplings. The accuracy was 0.869, the kappa consistency was 0.709, and the AUC was 0.913. When ALBI score, ALT and CEA were used to diagnose liver metastasis of colorectal cancer alone, the AUC of CEA was the largest (0.897), and the combination of the three had the highest efficacy in the diagnosis of liver metastasis of colorectal cancer. In the validation group, the AUC, sensitivity, specificity, C-index of the combined prediction of liver metastasis of colorectal cancer were 0.918, 85.0%, 95.6%, 0.918, respectively, and H-L fitting curve χ²=0.586, P=0.746.  Conclusions  ALBI score, ALT and CEA have certain predictive value for liver metastasis of colorectal cancer. The combined diagnosis of liver metastasis of colorectal cancer has high efficacy, and the risk prediction model constructed has a good predictive effect.