Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 ［95% confidence interval (CI) 0.70-0.97］ for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

Background Exposures to environmental pollution and specific occupational hazards exacerbate pulmonary fibrosis which has a complex pathogenesis and lacks effective therapeutic drugs. The extract from Dracocephalum moldavica L. can alleviate pulmonary fibrosis through anti-inflammatory and anti-pyroptosis pathways, but its mechanism of prevention and treatment for pulmonary fibrosis remains unclear. Objective To elucidate the targets and potential mechanism underlying the anti-pulmonary fibrosis efficacy of Dracocephalum moldavica L. extract by employing an amalgamation of network pharmacology and empirical verification. Methods The chemical composition of the extract of Dracocephalum moldavica L. was retrieved with the help of China National Knowledge Infrastructure (CNKI) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The disease targets related to pulmonary fibrosis were inquired using Gene Cards and DisGeNET. A protein-protein interaction (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The predicted potential targets were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses through the Database for Annotation, Visualization and Integrated Discovery (DAVID) and validated by molecular docking. Thirty-two rats were randomly divided into a control group, a model group, a low-dose group of Dracocephalum moldavica L. extract (100 mg·kg⁻¹), and a high-dose group of Dracocephalum moldavica L. extract (400 mg·kg⁻¹), with eight rats in each group. A rat model of pulmonary fibrosis was constructed using bleomycin (5 mg·kg⁻¹) intratracheal instillation, and an equal volume of saline was instilled into the control group. After modelling, 400 and 100 mg·kg⁻¹ of Dracocephalum moldavica L. extract were given the high-dose and low-dose groups by gavage, and an equal volume of saline was given by gavage to the control group and the model group, once per day, for consecutive 28 d. The animals were then neutralized, and lung tissues were collected. Structural changes in rat lung tissue were evaluated by observing stained pathological sections. Western blot (WB) was used to detect fibrosis-related proteins type I collagen (Col-I), α-smooth muscle actin (α-SMA), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) in lung tissues. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect α-SMA and Col-I mRNA levels in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in rats. Results A total of 378 key chemical components of the Dracocephalum moldavica L. extract and 1611 lung fibrosis-related targets were identified. Among them, 574 potential targets of Dracocephalum moldavica L. extract acting on lung fibrosis were obtained. The key targets determined by Degree value were albumin (ALB), tumour necrosis factor (TNF), AKT1, etc. The results of KEGG analysis suggested that the potential targets of Dracocephalum moldavica L. extract against pulmonary fibrosis mainly involved the PI3K-AKT, HIF-1 signaling pathway, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the binding energy between the active components (quercetin, apigenin, aesculetin, quercitrin) of Dracocephalum moldavica L. extract and the core targets of pulmonary fibrosis (TNF, IL-6, ALB, AKT1) were all <-29.288 kJ·mol⁻¹, indicating good binding ability. The animal validation results showed that compared with the control group, the rats in the model group had disrupted alveolar structure, obvious inflammatory cell infiltration, positive blue-striped collagen fibre deposition, and increased Col-I and α-SMA protein expression and transcription levels (P<0.001), p-PI3K and p-AKT expression levels (P<0.001), and levels of inflammatory factors TNF-α, IL-6, and IL-1β (P<0.001). Compared with the model group, the high- and low-dose groups of Dracocephalum moldavica L. extract alleviated the progression of pulmonary fibrosis, reduced inflammatory cell infiltration, and attenuated collagen fibre deposition in rats, with a decrease in the protein expression and transcription levels of Col-I and α-SMA (P<0.01), the expression levels of p-PI3K and p-AKT (P<0.001), and the levels of inflammatory factors IL-6 and TNF-α (P<0.05, P<0.001). Conclusion Dracocephalum moldavica L. extract manifests anti-pulmonary fibrotic properties through the modulation of the PI3K-AKT signaling cascade and the suppression of inflammatory reactions.

Objective:To establish a HPLC characteristic spectrum method of Centipeda minima based on standard decoction; To evaluate the correlation of materia medica, decoction pieces, standard decoction, intermediates and formula granule; To provide a reference for the quality standard research of Centipeda minima formula granules.Methods:The materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima were analyzed by a HPLC characteristic spectrum method, and the software "Similarity Evaluation System for Chromatographic Fingerprint of TCM" was employed to conform the common peaks. The clustering analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were adopted to find out the correlation of materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima. The Iconic components which can make differences was screened at the same time.Results:The characteristic chromatogram of materia medica, decoction pieces, standard decoction, intermediates and formula granules of Centipeda minima shared high similarity with the respective control chromatogram. Fourteen common peaks were confirmed, and eleven chromatographic peaks were identified. The results of CA and PCA were consistent, and the standard decoction, intermediates and formula granules of Centipeda minima were closer. Six differential components with VIP values greater than 1 were screened by OPLS-DA.Conclusions:The method is stable, accurate and characteristic. The study can provide a reference for the quality standard research of Centipeda minima Formula Granules by analyzing the correlation of characteristic spectrum of materia medica, decoction pieces, standard decoction, intermediates and formula granules.

Objective:Based on latent profile analysis, the category characteristics of decisional dilemma of participating in thrombolysis decision-making agents of patients with acute myocardial infarction (AMI) are analyzed to reduce the decision-making difficulties of decision-making agents in AMI patients.Method:The 292 cases of decision-making agents of patients with AMI and treated by intravenous thrombolysis in emergency department of Xinjiang Uygur Autonomous Region People's Hospital were selected as respondents From January 2022 to June 2023.A cross-sectional survey was conducted using General Information Questionnaire, Perceived Social Support Scale, State-Trait Anxiety Inventory, Control Preference Scale, Wake Forest Physician Trust Scale and Decisional Conflict Scale.Selected Mplus 8.3 software to conduct potential profile analysis on the survey data.Results:The 281 valid questionnaires were ultimately collected, with 146 males and 135 females aged 35-72(55.61 ± 9.05) among 281 AMI patients; 135 acting decision-makers from the south, 146 females, aged 30-72(55.52 ± 6.74).The score of decisional dilemma of participating in thrombolysis of decision-making agents of patients with AMI was 45(41, 46). LPA analysis showed that decisional dilemma of participating in thrombolysis of decision-making agents can be divided into 4 latent profiles which were low-level decisional dilemma profile accounts for 16.01% (45/281), high-level decisional dilemma profile accounts for 16.38% (46/281), extra high-level decisional dilemma profile with social support restricting accounts for 35.23% (99/281) and extra high-level decisional dilemma profile with information restricting accounts for 32.28% (91/281). Multiple logistic regression analysis showed represented patients with AMI history, decision-making agent ′s age, gender, educational level, decision-making role, decision-making participation type were significant influencing factors of decisional dilemma of participating in thrombolysis of high-level decisional dilemma profile (all P<0.05);represented patients with AMI history, decision-making agent ′s age, gender, education level, decision-making role, assuming patient ′s treatment payment role, assuming patient ′s care role, perceived social support level, state anxiety level, decision-making participation type and trust doctors level were significant influencing factors of decisional dilemma of participating in thrombolysis of extra high-level decisional dilemma profile with social support restricting and extra high-level decisional dilemma profile with information restricting(all P<0.05). Conclusions:The level decisional dilemma of participating in thrombolysis of decision-making agents for intravenous thrombolysis treatment of AMI patients were high, and their decisional dilemma can be divided into low-level decisional dilemma profile, high-level decisional dilemma profile, extra high-level decisional dilemma profile with social support restricting and extra high-level decisional dilemma profile with information restricting.They should be purposively intervened based on their corresponding decisional dilemma profile.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAc^CRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAc^CRH neurons during wakefulness and rewarding stimulation. Activation of NAc^CRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAc^CRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAc^CRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAc^CRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Animals ; Septal Nuclei/metabolism* ; Nucleus Accumbens/physiology* ; Corticotropin-Releasing Hormone/metabolism* ; Wakefulness/physiology* ; Neurons/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology* ; Anxiety/physiopathology* ; Reward

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Objective To investigate clinical and epidemiological features of pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients. Methods Clinical data of 68 kidney transplant recipients admitted from July, 2021 to December, 2021 were collected. All patients were divided into the PJP group (n=11), common pulmonary infection group (n=24) and non-pneumonia group (n=33) according to the status of pulmonary infection. The incidence and treatment of PJP after kidney transplantation were analyzed. Basic characteristics and laboratory parameters of the recipients were compared among all groups. The genotyping and transmission map of PJP patients were evaluated. Results Among 64 kidney transplant recipients, 11 cases were definitely diagnosed with PJP. The most common clinical manifestations included elevated body temperature, and dry cough complicated with progressive dyspnea. Chest CT scan showed diffuse interstitial inflammation and ground glass-like lesions of bilateral lungs in all patients. After diagnosis, all patients were orally given with compound sulfamethoxazole for 3-4 weeks. Two patients received non-invasive ventilator-assisted ventilation due to severe lung infection and dyspnea, and the remaining patients were given with nasal cannula oxygenation. One patient experienced elevated serum creatinine level upon discharge, and developed renal allograft failure. The remaining 10 recipients with PJP obtained normal renal allograft function, and no recipient died. Compared with the non-pneumonia group, the rejection rate was higher, the length of hospital stay was longer, the lymphocyte count was less, the lymphocyte proportion was lower, the levels of C-reactive protein, serum creatinine and lactate dehydrogenase were higher, and the levels of serum albumin was lower and CD4⁺T cell count was less in the PJP group (all P < 0.05). Compared with common pulmonary infection group, the lymphocyte count was less, the lymphocyte proportion was lower, the CD4⁺T cell count was less and 1, 3-β-D- glucan (BDG) level was higher in the PJP group (all P < 0.05). No new genotype was detected in 10 of the 12 testing samples. It was considered that PJP mainly depended on two transmission chains and two independent transmission individuals. Conclusions Kidney transplant recipients are prone to pneumocystis jirovecii (PJ) infection due to impaired cellular immune function. The most common clinical manifestations consist of elevated body temperature and dry cough complicated with progressive dyspnea, accompanied by headache and fatigue in partial patients. Chest CT scan shows diffuse interstitial inflammation and ground glass-like lesion of bilateral lungs. PJ may be transmitted through respiratory tract. Small-scale PJP might occur in the follow-up outpatient of kidney transplant recipients. Preventive measures should be delivered in a timely manner.

OBJECTIVE: To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. METHODS: A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. RESULTS: 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CONCLUSION CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.
Humans ; Male ; Azoospermia/genetics* ; DNA Copy Number Variations ; Oligospermia/genetics* ; Infertility, Male/genetics* ; Y Chromosome