Regulation of Notch Signaling Pathway to Innate Lymphoid Cells in Patients with Acute Myocardial Infarction.

The Notch signaling pathway is an important regulator in fate decisions and immune responses of innate lymphoid cells (ILCs). However, the function of Notch signaling in ILCs in acute coronary syndrome is still not fully elucidated. Thirty-one unstable angina pectoris (UAP) patients, 21 acute myocardial infarction (AMI) patients, and 20 controls were included in this study. Peripheral blood mononuclear cells (PBMCs) were isolated. The mRNA expression levels of Notch receptors and ligands were measured by real-time PCR, while ILC subsets were measured by flow cytometry. Lin- cells were purified and stimulated with γ-secretase inhibitor (GSI). ILC subsets, transcription factors, and secreted cytokines were assessed. Notch receptor and ligand mRNA levels were elevated in PBMCs and peripheral lin- cells from AMI patients. There was no significant difference in total lin-CD45+CD161+CD127+ ILC frequency among three groups. The CRTH2-CD117- ILC1 subset was down-regulated, while the CRTH2+ ILC2 subset was up-regulated in AMI patients. The CRTH2-CD117+ ILC3 subpopulation was comparable among the three groups. ILC1% was negatively correlated with Notch1 and Notch2 in AMI patients. Inhibition of Notch signaling pathway by GSI induced elevations in ILC1 frequency, T-bet mRNA expression, and interferon-γ secretion and reduced ILC2 frequency, GATA3 mRNA levels, and interleukin-5/interleukin-13 production by lin- cells from AMI patients. The current data indicated that activation of Notch signaling pathway might contribute to ILC1-to-ILC2 shift in peripheral blood in AMI patients.

Design and Analysis of Systematic Batched Network Codes.

Systematic codes are of important practical interest for communications. Network coding, however, seems to conflict with systematic codes: although the source node can transmit message packets, network coding at the intermediate network nodes may significantly reduce the number of message packets received by the destination node. Is it possible to obtain the benefit of network coding while preserving some properties of the systematic codes? In this paper, we study the systematic design of batched network coding, which is a general network coding framework that includes random linear network coding as a special case. A batched network code has an outer code and an inner code, where the latter is formed by linear network coding. A systematic batched network code must take both the outer code and the inner code into consideration. Based on the outer code of a BATS code, which is a matrix-generalized fountain code, we propose a general systematic outer code construction that achieves a low encoding/decoding computation cost. To further reduce the number of random trials required to search a code with a close-to-optimal coding overhead, a triangular embedding approach is proposed for the construction of the systematic batches. We introduce new inner codes that provide protection for the systematic batches during transmission and show that it is possible to significantly increase the expected number of message packets in a received batch at the destination node, without harm to the expected rank of the batch transfer matrix generated by network coding.

Vicious circle of family dysfunction and adolescent internet addiction: Do only child and non-only child exhibit differences?

The primary aim of the current study was to probe the longitudinal relationships between family dysfunction (FD) and adolescent Internet addiction (IA), as well as the group difference between only child and non-only child. Data were from a three-wave longitudinal data of 1301 Chinese adolescents, collected when adolescents were at Grade 7, Grade 8, and Grade 9. FD and IA were assessed via adolescent self-reported questionaries of Chinese Family Assessment Instrument and Internet Addiction Test. Cross-lagged panel model was constructed to estimate possible associations between FD and adolescent IA after controlling for demographic variables. Our results suggest that adolescents might get stuck in a vicious cycle of dysfunctional family and addictive Internet use: adolescents who lived in a dysfunctional family showed increased risk in IA in the subsequent year; in turn, adolescent IA further increased the possibility of FD. Moreover, multigroup comparison analysis revealed that the vicious cycle between FD and adolescent IA could be applied to both the only child and the non-only child. The findings may enrich the application of the Developmental Contextualism Theory and contribute to the identification of the starting points for intervention strategies of adolescent IA.

Sulforaphane protects myocardium from ischemia-reperfusion injury by regulating CaMKIIN2 and CaMKIIδ.

Myocardial ischemia/reperfusion (I/R) injury poses a significant threat to human health. High level of reactive oxygen species (ROS) and calcium overload are the foremost causes of myocardial damage in I/R. Sulforaphane (SFN) is known for its promising antioxidant effect. Whether or not SFN has myocardial protective effect against I/R is largely unknown. This study aimed to investigate if SFN can protect myocardium from I/R injury. We found that mice or cells pre-treated with SFN showed improved cardiac functions and cell survival. SFN treatment inhibited the production of inflammatory cytokines and the increase of intracellular calcium induced by hypoxia-reperfusion (H/R), while mitochondria membrane potential was effectively maintained. Transcriptome analysis showed that CaMKIIδ expression was down-regulated by SFN treatment in I/R myocardium, while CaMKIIN2, the inhibitor of CaMKII, was upregulated. Knockdown of CaMKIIN2 not only led to increased level of total CaMKIIδ and the phosphorylated CaMKIIδ but also blocked the pro-survival effect of SFN for H/R cells. Moreover, CaMKIIN2 overexpression was sufficient to suppress CaMKIIδ activation and improve cell survival under H/R. Taken together, this study demonstrated that SFN exerts cardioprotective effect toward I/R injury through upregulating CaMKIIN2 and down-regulating CaMKIIδ.

C-Reactive Protein-to-Albumin Ratio Predicts Sepsis and Prognosis in Patients with Severe Burn Injury.

BACKGROUND: Sepsis is a leading cause of mortality among severe burns. This study was conducted to investigate the predictive role of C-reactive protein-to-albumin ratio (CAR) for sepsis and prognosis in severe burns. METHODS: Patients with severe burn injuries from 2013 to 2017 were enrolled and divided into septic and nonseptic groups based on the presence of sepsis within 30 days postburn. Independent risk factors for sepsis were performed by the univariate and multivariate logistic regression analyses. The association between CAR level at admission and postburn 30-day mortality was designed via the Kaplan-Meier method. RESULTS: Of all the 196 enrolled patients, 83 patients developed sepsis within 30 days postburn injury, with an incidence of 42.3%. TBSA percentage (OR: 1.65, 95% CI: 1.17-2.32, P = 0.014) and CAR at admission (OR: 2.25, 95% CI: 1.33-3.56, P = 0.009) were the two independent risk factors for sepsis in severe burns by the multivariate logistic regression analysis. A higher CAR level (≥1.66) at admission was associated with a lower postburn 30-day survival rate (P = 0.005). CONCLUSIONS: The CAR level at admission was an independent risk factor for sepsis and prognosis in severe burns.

TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway.

TRIM59 has been recently implicated in the carcinogenesis of several cancers such as lung cancer, gastric cancer, and bladder cancer. However, its expression pattern and clinical significance has not been investigated in human breast cancer. In the present study, we examined TRIM59 protein expression in 95 cases of breast cancer tissues using immunohistochemistry. We found that TRIM59 was upregulated in 42 out of 95 cases and correlated with TNM stage (P = 0.0056), lymph node metastasis (P = 0.0088) and poor prognosis (P = 0.0092). Importantly, TRIM59 level was higher in triple-negative breast cancer (TNBC) (P = 0.0157). Expression of TRIM59 protein was also upregulated in breast cancer cell lines compared to normal MCF-10A cell line. TRIM59 plasmid and shRNA transfection was performed in MCF-7 and SK-BR-3 cells respectively. TRIM59 overexpression promoted cell proliferation, invasion, migration, cell cycle transition, and paclitaxel resistance, whereas TRIM59 depletion showed the opposite results. Further analysis showed that TRIM59 overexpression upregulated expression of cyclinA, cyclinE, Bcl-xl, Bcl-2, p-AKT, and downregulated expression of p21, p27, p53. AKT inhibitor treatment abolished the effect of TRIM59 on Bcl-2 expression. TRIM59 overexpression also upregulated the level of p53 ubiquitination. In conclusion, TRIM59 overexpression correlates with poor prognosis and promotes malignant behavior through regulation of AKT pathway in human breast cancer.

HIV risk and sexual health among female migrants in China.

Sexual behavior is the dominant mode of HIV transmission in China, and young female migrants are among the populations at highest risk. This article examines how HIV-related risk behaviors among female migrants might vary according to workplace settings. Participants were young female migrants recruited from three workplace settings-factories, restaurants and entertainment venues. In a cross-sectional survey, we assessed 457 participants' sociodemographic characteristics, HIV/AIDS-related knowledge, condom use knowledge, sexual behaviors, condom use behavior and reproductive health factors. Participants working in entertainment venues were significantly more likely than those working in factories and restaurants to report sexual behavior, unprotected sex, multiple pregnancy terminations and sexually transmitted infections (STI). However, participants working in factories and restaurants reported significantly lower levels of HIV/AIDS knowledge, condom use knowledge, condom use self-efficacy and history of HIV/AIDS counseling and testing. Independent correlates of unprotected sex included employment in an entertainment venue, abortion history and sexual self-efficacy. Independent correlates of STI or genitourinary tract infection included employment in an entertainment venue, abortion history, recent migration and recent unprotected sex. These findings indicate a need for sexual and reproductive health interventions prioritizing young female migrants, and call for programs that can be incorporated into different workplace settings.

Multiple Abortions and Sexually Transmitted Infections Among Young Migrant Women Working in Entertainment Venues in China.

We conducted a survey of 358 young migrant women working in entertainment venues in China to explore the prevalence of and factors associated with two indicators of sexual and reproductive health: (1) multiple abortions and (2) the dual risk of sexually transmitted infections (STI) and abortion history. One quarter (25.4 percent) of the women in this sample had multiple abortions during their lifetime and, of those with any abortion history, 18.3 percent had had an abortion outside of a regulated health clinic. One-third (33.0 percent) of the sample had had an STI during the past year, and approximately one-fourth (23.7 percent) of those women did not receive STI treatment in a public hospital. Approximately one-fourth (23.5 percent) of the sample reported both a history of abortion and an STI during the past year. Women with a history of multiple abortions had significantly lower income levels, were more likely to have sex with clients and with husbands, and tended more to use alcohol before sex. Women who experienced both abortion and STI risks were more likely to report having had unprotected sex, genitourinary tract infections symptoms, anxiety, illicit drug use, and suicidal ideation. Enhanced efforts are needed to improve reproductive and sexual health for female migrants in urban China, particularly those working in entertainment venues.

Risky alcohol use among migrant women in entertainment venues in China.

AIMS: The aims of this study are to describe the prevalence of hazardous drinking among migrant women working in entertainment venues in an urban setting in China and to identify specific risk factors and locations where hazardous drinking occurs. METHODS: From March to July 2012, we conducted a cross-sectional survey of 358 young migrant women working in entertainment venues in the capital city of Hefei, Anhui Province, China. Participants were asked about information regarding their demographic characteristics, sexual behavior, mental health, alcohol use and drug use. RESULTS: Overall, 203 (57%) participants had an AUDIT score ≥8 (risky drinking) and 95 (27%) women had an AUDIT ≥16 (probable dependence). Greater likelihood of probable alcohol dependence was associated with being younger (OR = 0.85, 95% CI: 0.76-0.95), working at an affluent venue (OR = 2.46, 95% CI: 1.13-5.36) and depressive symptoms during the past week (OR = 2.74, 95% CI = 1.10-6.83). CONCLUSION: Our study documents risky drinking practices among female migrants, irrespective of whether or not women reported engaging in commercial sex, working in entertainment venues. Our data suggest that entertainment venues, particularly those that are higher end (i.e. affluent) venues, should be targeted for public health interventions aimed to reduce harmful drinking practices.

HIV-related risk among female migrants working in entertainment venues in China.

China has experienced a surge in internal migration during the past decade, and migrant populations have been identified as a high-risk group for HIV and other sexually transmitted infections (STIs). Young female migrants often find employment in entertainment venues (bars, karaoke parlors, and massage parlors) located in metropolitan cities, and sex work transactions frequently occur in these venues. We examined factors associated with risk for HIV, other STIs, and reproductive health challenges in a cross-sectional study of 358 young female migrants, ages 18-29, working in entertainment venues in a rapidly growing urban city in China. Results indicate high levels of behavioral risk for HIV and other STIs, low rates of HIV testing, and high prevalence of problem drinking and mental health problems, including recent depression symptoms and suicidal ideation. Factors associated with increased STIs and genitourinary tract infections included commercial sex work, early sexual debut, abortion history, illicit drug use, and anxiety. Factors associated with increased HIV testing included employment in an affluent entertainment venue, education level, knowledge about where to obtain free HIV tests, condom use, and general HIV/AIDS knowledge. Findings of this study highlight the insufficient coverage of current public health services to female migrants working in entertainment venues and call for more assertive prevention interventions to mitigate risk for sexual, reproductive, behavioral, and mental health problems in this mobile population.

[The status of HIV disclosure to primary sexual partners and sexual behaviors among HIV-infected men who have sex with men of 3 cities in China].

OBJECTIVE: To investigate the status of HIV disclosure to primary partners and to explore the correlates of HIV disclosure among HIV-infected men who have sex with men (MSM) in Guangzhou, Chongqing and Chengdu. METHODS: This survey was conducted in Chengdu, Chongqing and Guangzhou by using "snowballing" sample from December, 2012 to May, 2013. Participants who were eighteen years old or elder, HIV-infected, had sex with men and lived in three cities when the survey was conducted were eligible for subjects of this survey. Primary partners and disclosure status of participants were investigated. Multiple Unconditioned Logistic Regression analysis was used to analyze the influence factors associated with HIV disclosure.Of 600 participants, 541 were excluded because of logical problem or incomplete items in questionnaire and the effective response rate was 90.2%. RESULTS: Of the 541 HIV-positive MSM participants, the mean age was (30.2 ± 7.7) years old, 78.2% (423/541) of the participants had male primary partners.Of the 423 participants who had male primary partner, 10.9% (46/423) had wife, 58.9% (249/423) had one primary partner, and 41.1% (174/423) had two or more. The proportion of HIV disclosure to all male primary sexual partners and wife was 41.8% (177/423) and 4.5% (19/423) respectively, 20.3% (86/423) of them disclosure to some of male primary partners and 37.8% (160/423) not disclosure to any male primary partners. Participants who had HIV-positive male partners in the past 6 months (accounting for 35.2% (149/423)) were more likely to disclose HIV infection to their primary sexual partners (70.5% (105/149)) than those who had non-HIV-positive sexual partners (26.3% (72/274)) (χ(2) = 77.46, P < 0.01). Participants who had male unknown HIV-status sexual partners in the past 6 months(accounting for 52.7% (223/423)) were less likely to disclosure HIV infection to primary sexual partners (22.4% (50/223) ) than those who had already known HIV-status sexual partners (63.5% (127/200)) (χ(2) = 73.11, P < 0.01). The possibility of HIV disclosure to primary sexual partner among participants who had HIV-positive sexual partner increase to 6.36 (3.75-10.80) times of those who had HIV -negative partners, and the possibility among participants who had sexual partners of unknown HIV status decreased to 0.44 (0.25-0.76) times of those who had sexual partners of already known HIV status. Compared with having non-anal sex behaviors with male primary partner, the possibility of HIV disclosure to primary sexual partner decreased to 0.46 (0.22-0.95) times among participants who had anal sex behavior with male primary partners. CONCLUSION: There were low proportion of HIV disclosure to primary sexual partners among HIV-infected MSM in Guangzhou, Chongqing and Chengdu.HIV disclosure to primary sexual partners may be associated with characteristics of their sexual partners, and participants who had HIV-positive male partners were more likely to disclose HIV infection to their primary sexual partners.

Surface maturation scoring for oesophageal squamous intraepithelial neoplasia: a novel diagnostic approach inspired by first endomicroscopic 3-dimensional reconstruction.

OBJECTIVE: Loss of surface maturation and cytonuclear atypia have been regarded as the pathological 'gold standard' for the diagnosis of oesophageal squamous cell intraepithelial neoplasia. However, there has been no satisfactory endomicroscopic method similar to this pathological approach to detect surface maturation and screen for oesophageal squamous cell intraepithelial neoplasia. The aim of this study was to apply a 3-dimensional (3D) confocal endomicroscopic imaging technique to investigate the surface maturation of the oesophageal epithelium and develop new 2-dimensional confocal endomicroscopic criteria based on surface maturation. DESIGN: In the 3D reconstruction phase, intrapapillary capillary loops were reconstructed to demonstrate the stereo configuration of the oesophageal epithelium, and a novel surface maturation scoring (SMS) method for plane confocal images was developed based on the interpretation of the 3D microstructure. In the SMS diagnostic phase, 1214 patients were screened and confocal images from 64 non-invasive oesophageal lesions were independently evaluated using SMS and previous methods. RESULTS: We successfully obtained and interpreted 3D confocal images of the human oesophageal epithelium for the first time. The sensitivity (81.0%, 95% CI 58.1% to 94.6%) and specificity (90.7%, 95% CI 77.9% to 97.4%) of the newly established SMS were superior to previous confocal approaches in distinguishing squamous intraepithelial neoplasia from other non-invasive lesions. CONCLUSIONS: 3D confocal endomicroscopic imaging provides valuable insight into the stereo configuration of the human oesophageal epithelium. SMS is a novel and promising diagnostic method to distinguish neoplasia during ongoing endoscopy.

Prognostic value of hemoglobin in patients with sepsis: A systematic review and meta-analysis.

BACKGROUND: Sepsis patients have a high mortality rate and are frequently anemic. The importance of early detection and blood transfusion treatment cannot be overstated. OBJECTIVE: A systematic review and meta-analysis of published literature was conducted to evaluate the association between hemoglobin and the prognosis of patients with sepsis. METHODS: The PubMed, Embase, Cochrane Library and Chinese Biomedical Literature (CBM) databases were searched from inception to May 21, 2023. Pediatric patients were excluded, and there were no language restrictions. A random effects model was used to calculate pooled odds ratios to assess the relationship between hemoglobin and prognosis in sepsis. RESULTS: There were 110,004 patients included in 9 studies, of which 51,568 had a poor prognosis. The results of univariate and multivariate analyzes showed that hemoglobin was associated with the prognosis of patients with sepsis (univariate OR: 1.35, 95 % confidence interval (CI): 1.16-1.58; multivariate OR: 1.26, 95 % CI: 1.13-1.40). Dose-response meta-analysis showed that there was a nonlinear relationship between hemoglobin level and prognosis in patients with sepsis. CONCLUSION: The level of hemoglobin at admission is related to the prognosis of patients with sepsis, and decreases in hemoglobin level are associated with an increase in the mortality rate of patients with sepsis. Therefore, early transfusion of red blood cells should be performed in patients with sepsis, and early attention should be given to anemia in patients with sepsis. However, more robust studies are needed to further determine the level of early hemoglobin maintenance in patients with sepsis.

The effect of sitting baduanjin in patients with ST-segment elevation acute myocardial infarction after percutaneous coronary intervention: A quasi-experimental study.

BACKGROUND: Early cardiac rehabilitation plays a crucial role in the recovery of patients with ST-segment elevation acute myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). This study sought to determine the effect of a program of sitting Baduanjin exercises on early cardiac rehabilitation. OBJECTIVE: The goal of this study was to investigate the effects of sitting Baduanjin exercises on cardiovascular and psychosocial functions in patients with STEMI following PCI. METHODS: This quasi-experimental study employed a randomized, non-equivalent group design. Patients in the intervention group received daily sitting Baduanjin training in addition to a series of seven-step rehabilitation exercises, whereas those in the control group received only the seven-step rehabilitation training, twice daily. Differences in heart rate variability (HRV) indicators, exercise capacity (Six-Minute Walking Distance; 6-MWD), anxiety (Generalized Anxiety Disorder-7; GAD-7), and depression (Patient Health Questionnaire-9; PHQ-9) between the two study groups during hospitalization were analyzed. RESULTS: Patients in the intervention group exhibited lower rates of abnormalities in the time domain and frequency domain parameters of HRV. The median scores of GAD-7 and PHQ-9 in both groups were lower than those at the time of admission, with the intervention group exhibiting lower scores than the control group (P < 0.001; P < 0.001, respectively). The 6-MWD after the intervention was greater in the intervention group compared to the control group (P = 0.014). CONCLUSIONS: We found that sitting Baduanjin training has the potential to enhance HRV, cardiac function, and psychological well-being in patients with STEMI after PCI. This intervention can potentially improve the exercise capacity of a patient before discharge.

[Retrospective Study of Bronchoscopic Intervention Therapy for Bronchopleural Fistula Induced by Pulmonary Surgery].

BACKGROUND: As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. METHODS: Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. RESULTS: For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. CONCLUSIONS: BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Co-delivery of siBcl-2 and PTX with mitochondria-targeted functions to overcoming multidrug resistance.

Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary pharmaceutical agent for treating recurrent and metastatic breast cancer, the emergence of PTX resistance frequently results in therapeutic shortcomings, representing a substantial obstacle in clinical breast cancer management. In response, we developed a delivery system exhibiting dual specificity for both tumors and mitochondria. This system facilitated the sequential administration of small interfering B-cell lymphoma-2 (siBcl-2) and PTX to the tumor cytoplasm and mitochondria, respectively, with the aim of surmounting PTX resistance in tumor cells through the activation of the mitochondrial apoptosis pathway. Notably, we employed genetic engineering techniques to fabricate a recombinant ferritin containing the H-subunit (HFn), known for its tumor-targeting capabilities, for loading siBcl-2. This HFn-siBcl-2 complex was then combined with positively charged Triphenylphosphine-Liposome@PTX (TL@PTX) nanoparticles (NPs) to formulate HFn/siBcl-2@TL/PTX. Guided by HFn, these nanoparticles efficiently entered cells and released siBcl-2 through the action of triphenylphosphine (TPP)-mediated "proton sponge," thereby precisely modulating the expression of Bcl-2 protein. Simultaneously, PTX was directed to the mitochondria through the accurate targeting of TL@PTX, synergistically initiating the mitochondrial apoptosis pathway and effectively suppressing PTX resistance both in vitro and in vivo. In conclusion, the development of this dual-targeting delivery system presents a promising therapeutic strategy for overcoming PTX resistance in the clinical treatment of breast cancer.

[A Case of Multidomain Integrated Treatment Strategy 
for Complex Primary Pulmonary Sarcomatoid Carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
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The antidepressant effect of Shexiang Baoxin Pills on myocardial infarction rats with depression may be achieved through the inhibition of the NLRP3 inflammasome pathway.

BACKGROUND: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). METHODS: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence. RESULTS: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1ß, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1ß, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. CONCLUSION: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.).

Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B.

Signal peptide (SP) is essential for protein secretion, and pathogenic variants in the SP of FIX have been identified in hemophilia B (HB). However, the underlying mechanism for the genotype-phenotype correlation of these variants has not been well studied. Here we systematically examined the effects of 13 pathogenic point variants in the SP of FIX using different approaches. Our results showed that these point variants lead to HB by missense variants and/or aberrant pre-mRNA splicing. The missense variants in h-region mainly affected the co-translational translocation function of the SP, and those in c-region caused FIX deficiency mainly by disturbing the co-translational translocation and/or cleavage of the SP. Almost absolute aberrant pre-mRNA splicing was only observed in variants of c.82T>G, but a slight change of splicing patterns was found in variants of c.53G>T, c.77C>A, c.82T>C, and c.83G>A, indicating that these variants might have different degree to affect pre-mRNA splicing. Although two 6-nt deletion aberrant pre-mRNA splicing products caused FIX deficiency by disturbing the SP cleavage, but they could produce some functional mature FIX and vitamin K could increase the secretion of functional FIX. Taken together, our data indicated that pathogenic variants in the SP of FIX caused HB through diverse molecular mechanisms or even a mixture of several mechanisms, and vitamin K availability could be partially attributed to varying bleeding tendencies in patients carrying the same variant in the SP.

Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. METHODS: Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF(+/-) mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF(+/+) mice following different doses of BDNF administration. RESULTS: Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF(+/-) than in BDNF(+/+) mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF(+/-) mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF(+/+) mice. CONCLUSIONS: The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.