OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

[Objective] To explore the influencing factors of quality monitoring index on the nucleic acid pooling detection mode and continuously improve the detection quality of nucleic acid laboratory. [Methods] The quality monitoring indicators (NAT reactive rate, NAT resolution reactive rate, NAT invalid batch rate, NAT invalid result rate, equipment failure rate) and causes of invalidity in our laboratory from January 1, 2020 to December 31, 2022 were retrospectively analyzed. The quality monitoring indicators of the laboratory during 2020 to 2022 were compared longitudinally. The quality monitoring indicators of the laboratory in 2022 were compared horizontally with the overall level in Shandong for the same period to find the differences. [Results] From 2020 to 2022, a total of 218 686 samples were detected, the NAT reactive rate was 0.15‰ (32 samples in total), the resolution reactive rate was 39.02%, the invalid batch rate was 1.06%, the invalid result rate was 1.18%, and the equipment failure rate was 3.58%. There were no differences in the NAT reactive rate, NAT resolution reactive rate and NAT invalid batch rate among different years (P>0.05), but there were differences in the invalid result rate (P<0.05). Equipment failure was the main cause of invalid results (56.53%). Compared with other laboratories in Shandong, there were differences in the NAT reactive rate and invalid result rate (P<0.05). There were differences in the reaction rate, resolution rate and invalid result rate among different reagents (P<0.05). Compared with other two laboratories using the same manufacturer's reagent, there were differences in the reactive rate and invalid result rate (P<0.05), but no difference in the resolution rate and invalid batch rate (P>0.05). [Conclusion] Establishing quality indexes for process control and regular analysis can timely detect potential risks in laboratory operation. The use of quality indicators to implement self-comparison and inter-laboratory comparison can help the laboratory systematically and scientifically evaluate its own operating status and formulate corresponding quality management strategies, thereby improving the laboratory's testing capacity and ensure the safety of blood use.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

[This corrects the article DOI: 10.1016/j.apsb.2020.12.008.].

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

OBJECTIVE: To investigate the relationship between mean perfusion pressure (MPP) and the risk of sepsis-associated acute kidney injury (SA-AKI) and its prognosis, and to determine the optimal cut-off value of MPP for predicting SA-AKI. METHODS: A retrospective cohort study was conducted. The clinical data of adult patients with sepsis were collected from the Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2) database. The patients were divided into two groups based on the occurrence of SA-AKI. Baseline characteristics, vital signs, comorbidities, laboratory indicators within 24 hours of intensive care unit (ICU) admission, and clinical outcome indicators were collected. Mean MPP was calculated using the average values of mean arterial pressure (MAP) and central venous pressure (CVP), MPP = MAP-CVP. Cox regression models were constructed, relevant confounding factors were adjusted, and multivariate Logistic regression analysis was used to investigate the associations between MPP and the risk of SA-AKI as well as ICU death. The predictive value of MPP for SA-AKI was evaluated using receiver operator characteristic curve (ROC curve) analysis, and the optimal cut-off value was determined. RESULTS: A total of 6 009 patients were ultimately enrolled in the analysis. Among them, SA-AKI occurred in 4 755 patients (79.13%), while 1 254 patients (20.87%) did not develop SA-AKI. Compared with the non-SA-AKI group, the MPP in the SA-AKI group was significantly lowered [mmHg (1 mmHg≈0.133 kPa): 62.00 (57.00, 68.00) vs. 65.00 (60.00, 70.00), P < 0.01], and the ICU mortality was significantly increased [11.82% (562/4 755) vs. 1.59% (20/1 254), P < 0.01]. Three Cox regression models were constructed: model 1 was unadjusted; model 2 was adjusted for gender, age, height, weight and race; model 3 was adjusted for gender, age, height, weight, race, heart rate, respiratory rate, body temperature, hemoglobin, platelet count, white blood cell count, anion gap, HCO₃^-, blood urea nitrogen, serum creatinine, Cl^-, Na⁺, K⁺, fibrinogen, international normalized ratio, blood lactic acid, pH value, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, sequential organ failure assessment score, Charlson comorbidity index score, use of vasopressors, mechanical ventilation, and urine output. Multivariate Logistic regression analysis showed that when MPP was treated as a continuous variable, there was a negative correlation between MPP and the risk of SA-AKI in model 1 and model 2 [model 1: odds ratio (OR) = 0.967, 95% confidence interval (95%CI) was 0.961-0.974, P < 0.001; model 2: OR = 0.981, 95%CI was 0.974-0.988, P < 0.001], and also a negative correlation between MPP and the risk of ICU death (model 1: OR = 0.955, 95%CI was 0.945-0.965, P < 0.001; model 2: OR = 0.956, 95%CI was 0.946-0.966, P < 0.001). However, in model 3, there was no significant correlation between MPP and either SA-AKI risk or ICU death risk. when MPP was used as a multi-categorical variable, in model 1 and model 2, referring to MPP ≤ 58 mmHg, when 59 mmHg ≤ MPP ≤ 68 mmHg, as MPP increased, the risk of SA-AKI progressively decreased (OR value was 0.411-0.638, all P < 0.001), and the risk of ICU death also gradually decreased (OR value was 0.334-0.477, all P < 0.001). ROC curve showed that MPP had a certain predictive value for SA-AKI occurrence [area under the ROC curve (AUC) = 0.598, 95%CI was 0.404-0.746], and the optimal cut-off value was 60.5 mmHg. CONCLUSION MPP was significantly associated with the risk of SA-AKI, with an optimal cut-off value of 60.5 mmHg, and also demonstrated a significant correlation with the risk of ICU death.
Humans ; Acute Kidney Injury/physiopathology* ; Retrospective Studies ; Sepsis/physiopathology* ; Middle Aged ; Prognosis ; Male ; Female ; Aged ; Risk Factors ; Intensive Care Units ; Adult ; Logistic Models ; Proportional Hazards Models

OBJECTIVE To evaluate the clinical value of dose-escalated postoperative radiotherapy(PORT)in improving local control and survival outcomes for head and neck adenoid cystic carcinoma(ACC)patients.METHODS This retrospective study analyzed 336 ACC patients treated with surgery plus PORT at Beijing Tongren Hospital from January 2015 to January 2021.Cohort stratification compared high-dose(>60 Gy,n=146)and conventional-dose(≤60 Gy,n=190)regimens.Survival analysis employed Kaplan-Meier estimates with log-rank testing,complemented by multivariate Cox regression for risk adjustment.RESULTS The cohort demonstrated 39.29%(132/336)cumulative local failure rate.The overall survival rates at 1,3,and 5 years after surgery were 98.81%,94.05%,and 90.48%,respectively.Dose-response relationships revealed:1.Significantly reduced local recurrence with high-dose PORT(28.08%vs.47.89%,P<0.001),corresponding to 41.37%lower recurrence risk(a HR=0.59,95%CI=0.38-0.91;P=0.041);2.Superior progression-free survival in the high-dose group(3-year:86.99%vs.76.32%;5-year:82.19%vs.66.32%,all P<0.05);3.Comparable overall survival between groups(median OS:200 vs.160 months,P=0.292).CONCLUSION Dose escalation beyond 60 Gy significantly enhances locoregional control and progression-free survival in head and neck ACC without conferring overall survival advantage,likely reflecting the disease's characteristic indolent metastatic progression.These results establish>60 Gy as an optimal dose threshold for PORT in high-risk ACC management.

【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.