In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVES: To explore the measures to improve the follow-up rate of preterm infants after discharge, and to evaluate the effectiveness of these measures using quality improvement methodology. METHODS: The follow-up status of preterm infants discharged from March to May 2017 was used as the baseline before quality improvement, and a specific quality improvement goal for the follow-up rate was proposed. The Pareto chart was used to analyze the causes of follow-up failure, and a key driver diagram was constructed based on the links involved in improving follow-up rate. The causes of failure were analyzed to determine the key links and intervention measures for quality improvement, and the follow-up rate was monitored weekly using a control chart until the quality improvement goal was achieved. RESULTS: The follow-up rate of preterm infants after discharge was 57.92% (117/202) at baseline before quality improvement, and the quality improvement goal was set to increase the follow-up rate of preterm infants from baseline to more than 80% within 12 months. The Pareto chart analysis showed that the main causes of follow-up failure were deficiencies in follow-up file management and irregular follow-up times (33.70%, 31/92), insufficient follow-up education and poor communication (25.00%, 23/92), and the inability to meet the diverse needs of parents (18.48%, 17/92). Based on the key links for quality improvement and the main causes of follow-up failure, the following intervention measures were adopted: (1) strengthen follow-up publicity and education; (2) build a follow-up team; and (3) establish a follow-up platform and system. The control chart indicated that with the implementation of the above intervention measures, the weekly follow-up rate increased to 74.09% (306/413) in July 2017 and 83.09% (511/615) in December 2017, finally achieving the quality improvement goal. During the COVID-19 pandemic, the follow-up rate of preterm infants fluctuated between 23.54% (460/1 954) and 70.97% (1 931/2 721), and subsequently, it returned to pre-pandemic levels starting in February 2023. CONCLUSIONS The application of quality improvement methodology can help to formulate intervention measures based on the main causes of follow-up failure, thereby improving the follow-up rate of preterm infants after discharge. This quality improvement method is feasible and practical and thus holds promise for clinical application.
Humans ; Quality Improvement ; Infant, Premature ; Infant, Newborn ; Patient Discharge ; Follow-Up Studies ; Female ; Male

Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC₅₀ and CC₅₀ of compound 3 against HBV were 4.5 μmol·L^-1 and 92.3 μmol·L^-1, respectively. This is the first report of the antiviral activity of compound 3.

Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q₁, Q₃). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q₁, Q₃) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ²=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ²=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ²=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.
Enhanced Recovery After Surgery ; Female ; Gastrectomy ; Humans ; Length of Stay ; Male ; Pain ; Patient Outcome Assessment ; Postoperative Complications/surgery* ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

Objective To investigate the effect of Yipi Yanggan prescription on the malignant transformation of liver stem cells in liver precancerous lesion induced by diethylnitrosamine (DEN) and its possible molecular mechanism. Methods A total of 35 male Sprague-Dawley rats were randomly divided into normal control group (blank group), DEN model group (model group), DEN+Yipi Yanggan prescription group (Yipi Yanggan prescription group), and DEN+Hugan tablet group (Hugan tablet group), with 5 rats in the blank group and 10 rats in the other three groups. Intraperitoneal injection of DEN was performed to establish a model of liver precancerous lesion, the rats were sacrificed after 16 weeks of administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb) were measured; liver tissue was collected to observe the changes in size and appearance and calculate liver weight ratio (liver index); HE staining and Sirius Red staining were used to observe the pathological and morphological changes of rat liver tissue; immunohistochemistry was used to measure the expression of OV6 and glutathione S-transferase-Pi (GST-Pi); RT-PCR was used to measure the mRNA expression of EpCAM, CD133, and CD90, and Western blot was used to measure the protein expression of PI3K, Akt, and mTOR and their phosphorylation level. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the model group, the Yipi Yanggan prescription group and the Hugan tablet group had significant improvements in liver pathology and morphology, significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Compared with the Hugan tablet group, the Yipi Yanggan prescription group showed a more significant protective effect on the liver, with significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Conclusion Yipi Yanggan prescription can improve liver precancerous lesion induced by DEN in rats by inhibiting the malignant transformation of liver stem cells, and its mechanism of action may be associated with the PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.

Objective:To study the cytotoxicity and malignant transformation ability of chrysotile on MeT-5A cells.Methods:In June 2016, lactate dehydrogenase (LDH) method was used to detect the cytotoxicity of chrysotile to MeT-5A cells. MeT-5A cells were treated with 5 μg/cm 2 chrysotile intermittently for 24 h a time, once a week and a total of 28 times. After the cells showed anchorage independent growth, the cell features of malignant transformation were identified by colony forming frequency in soft agar, and the soft agar colony formation rates were calculated. The activities of key speed limiting enzymes of glycolysis metabolism including hexokinase (HK) , phosphofructokinase (PFK) and pyruvate kinase (PK) were determined by UV colorimetry. Results:Chrysotile was cytotoxic to MeT-5A cells in a concentration-dependent decline. Compared with the control group, the relative survival rates of MeT-5A cells were significantly decreased after exposed to chrysotile at 10, 20, 40 and 80 μg/cm 2 ( P<0.05) . After 28 times of exposure, the growth rate of the cells in chrysotile transformed MeT-5A cells was accelerated, the arrangement was disordered, the contact inhibition was lost, and the double layer growth appeared, which could grow on soft agar. The colony forming rate of the chrysotile transformed MeT-5A cells was 18.33‰±2.49‰. Compared with the control group (0) , the difference was statistically significant ( P<0.01) . The activities of glycolysis related kinase including PK [ (19.51±1.52) U/L], PFK[ (0.12±0.02) U/10 4 cell] and HK[ (0.26±0.01) U/10 4 cell] were increased in the chrysotile transformed MeT-5A cells compared with control group [ (25.00±1.04) U/L、(0.15±0.01) U/10 4 cell and (0.33±0.01) U/10 4 cell] ( P<0.01) . Conclusion:Chrysotile can induce malignant transformation of MeT-5A cells and increase the activities of glycolysis related kinases including PK, PFK and HK.

Objective:To study the cytotoxicity and malignant transformation ability of chrysotile on MeT-5A cells.Methods:In June 2016, lactate dehydrogenase (LDH) method was used to detect the cytotoxicity of chrysotile to MeT-5A cells. MeT-5A cells were treated with 5 μg/cm 2 chrysotile intermittently for 24 h a time, once a week and a total of 28 times. After the cells showed anchorage independent growth, the cell features of malignant transformation were identified by colony forming frequency in soft agar, and the soft agar colony formation rates were calculated. The activities of key speed limiting enzymes of glycolysis metabolism including hexokinase (HK) , phosphofructokinase (PFK) and pyruvate kinase (PK) were determined by UV colorimetry. Results:Chrysotile was cytotoxic to MeT-5A cells in a concentration-dependent decline. Compared with the control group, the relative survival rates of MeT-5A cells were significantly decreased after exposed to chrysotile at 10, 20, 40 and 80 μg/cm 2 ( P<0.05) . After 28 times of exposure, the growth rate of the cells in chrysotile transformed MeT-5A cells was accelerated, the arrangement was disordered, the contact inhibition was lost, and the double layer growth appeared, which could grow on soft agar. The colony forming rate of the chrysotile transformed MeT-5A cells was 18.33‰±2.49‰. Compared with the control group (0) , the difference was statistically significant ( P<0.01) . The activities of glycolysis related kinase including PK [ (19.51±1.52) U/L], PFK[ (0.12±0.02) U/10 4 cell] and HK[ (0.26±0.01) U/10 4 cell] were increased in the chrysotile transformed MeT-5A cells compared with control group [ (25.00±1.04) U/L、(0.15±0.01) U/10 4 cell and (0.33±0.01) U/10 4 cell] ( P<0.01) . Conclusion:Chrysotile can induce malignant transformation of MeT-5A cells and increase the activities of glycolysis related kinases including PK, PFK and HK.