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*

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Eleven compounds were isolated and purified from the ethyl acetate part of 80% ethanol extract of Ferula feruloides root by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 dextran gel column chromatography and semi-preparative liquid chromatography and then modern wave spectrometry methods (NMR, MS, UV, IR) were used to identify the structures of the compounds, which were identified as baigene D (1), baigene E (2), baigene F (3), β-kirialovin (4), α-kirialovin (5), falcarindiol (6), ammoresinol (7), dshamirone (8), 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4-methyl-5-(4-methy1-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin (9), 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadi-enyl]-furo[3,2-c]coumarin (10), and baigene C (11). Compounds 1-3 are new coumarin analogues, and compounds 4-6 are firstly isolated from F. feruloides. The anti-proliferative activity of compounds 5, 7-11 against human gastric cancer (MKN-45) cells was evaluated using MTT assay, which showed that compounds 7-11 exhibited strong inhibitory activity, and compound 5 exhibited weak inhibitory activity.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To analyse the clinical efficacy of low-frequency of midnight-noon ebb-flow acupuncture-opening method(also called Ziwu Liuzhu Acupuncture,referring to the needling method based on acupoints selection according to qi and blood movement following heavenly-stems and earthly-branches cycle)in treating low myopia in children.Methods A retrospective study was conducted to collect the clinical data of 84 cases(168 eyes)of children with low myopia who received treatment at the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from January 2021 to December 2022.The children were divided into two groups according to the different treatment protocols:42 cases(84 eyes)treated with acupuncture combined with conventional optometry as the control group,and 42 cases(84 eyes)treated with low-frequency of midnight-noon ebb-flow acupuncture-opening method combined with conventional optometry as the observation group,and the treatment course of both groups was 24 weeks.The changes of refractive error and axial length before and after treatment were observed,and the clinical efficacy in the two groups of children were evaluated.Results(1)After treatment,there being statistically significant differences in the refractive error between the two groups of the children(P＜0.05),and the differential value of the refractive error of the children between the two groups before and after treatment was statistically significant(P＜0.05).(2)After treatment,there being statistically significant differences in the axial length of the children in both groups(P＜0.05).The differential value of axial lengths of the children between the two groups before and after treatment was statistically significant(P＜0.05).(3)The total effective rate of the observation group was 84.52%(71/84),and which of the control group was 63.10%(53/84),the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The low-frequency of midnight-noon ebb-flow acupuncture-opening method in treating low myopia in children can effectively postpone the degree of myopia,and decrease the growth of the axis,with exact therapeutic effect.

Objective:To investigate the expression level of NME3 in gastric cancer and its correlation with clinicopathological characteristics and prognosis.Methods:A retrospective case series study was conducted. The clinicopathological data of 156 patients with gastric cancer who received radical gastrectomy in Zhejiang Cancer Hospital between January 2013 and December 2017 were collected. The samples of cancer tissues and paracancerous tissues were taken and partial paracancerous tissues were not meet the standard. Finally, immunohistochemical staining was conducted on both cancer tissues (156 cases) and paracancerous tissues (139 cases) to detect the expression of NME3 protein; H scoring system was used to score the expression of NME3 protein and the patients were divided into NME3 high expression group (H score ≥ 6 points) and NME3 low expression group (H score < 6 points). The clinicopathological characteristics of the 2 groups were analyzed. Kaplan-Meier method was used for overall survival (OS) analysis of the 2 groups, and log-rank test was used for comparison. Univariate and multivariate Cox proportional risk models were used to determine the poor independent factors affecting the poor OS in patients with gastric cancer.Results:The median age of the 156 patients was 61 years (53 years, 68 years), including 110 males (70.5%) and 46 females (29.5%). The proportion of patients with NME3 high expression in cancer tissues was lower than that in paracancerous tissues [51.9% (81/156) vs. 75.5% (105/139)], and the difference was statistically significant ( χ2 = 17.60, P < 0.001). The proportion of patients with NME3 high expression in moderate-low differentiation and moderate differentiation group was lower than that of those in low-differentiation group [63.3% (50/79) vs. 39.4% (28/71)], the proportion of patients with NME3 high expression in pTNM staging group Ⅲ-Ⅳ was higher than that of those in pTNM staging group Ⅰ-Ⅱ [55.5% (76/137) vs. 26.3% (5/19)], and the difference was statistically significant (both P < 0.05). The proportion of patients with NME3 high expression was 62.2% (46/74), 52.0% (13/25), 39.3% (22/56), respectively in patients with Lauran intestinal type, mixed type and diffused type, and the differences were statistically significant ( χ2 = 6.69, P = 0.035). In addition, OS of patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the difference was statistically significant ( P < 0.001). The further analysis of gender subgroup showed that OS of male patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and OS of female patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the differences was statistically significant (all P < 0.05). Univariate and multivariate Cox regression analysis showed that the expression of NME3 in cancer tissues (high expression vs. low expression: HR = 0.342, 95% CI: 0.207-0.564, P < 0.001), family history (yes vs. no: HR = 2.240, 95% CI: 1.285-3.907, P = 0.004), pN staging (N 2-3vs. N 0-1: HR = 2.133, 95% CI: 1.114-4.083, P = 0.022), pM staging (M 1vs. M 0: HR = 2.761, 95% CI: 1.386-5.500, P = 0.004), carcinoma embryonic antigen (CEA) level (CEA > 5 ng/ml vs. CEA ≤ 5 ng/ml: HR = 1.688, 95% CI: 1.018-2.798, P = 0.042), carbohydrate antigen 125 (CA125) level (CA125 > 35 U/ml vs. CA125 ≤ 35 U/ml: HR = 2.913, 95% CI: 1.403-6.047, P = 0.004) were independent factors influencing OS in patients with gastric cancer. Conclusions:NME3 is lowly expressed in gastric cancer tissues, and it is highly expressed in higher-differentially, late staged and intestinal type gastric cancer. NME3 low expression is an independent risk factor for the poor prognosis of gastric cancer. It is speculated that NME3 may play a inhibitory role in gastric cancer.

Objective: To compare the effectiveness of total laparoscopic versus laparoscopic-assisted distal gastrectomy and investigate the safety and replicability of total laparoscopic distal gastrectomy in older patients. Methods: This was a retrospective cohort study. The inclusion criteria were as follows: (1) age ≥65 years; (2) malignant gastric tumor diagnosed pathologically preoperatively; (3) Eastern Cooperative Oncology Group performance status score 0-1; (4) Grade I-III American Society of Anesthesiologists physical status; (5) preoperative clinical tumor stage I-III; (6) total laparoscopic or laparoscopic-assisted distal gastrectomy performed; and (7) gastrointestinal tract reconstruction using uncut Roux-en-Y or Billroth-II+Braun procedure. Patients who had received neoadjuvant therapy, undergone conversion to open surgery, or had serious comorbidities or incomplete data were excluded. The clinical data of 129 patients who met the above criteria and had undergone laparoscopic surgery for gastric cancer from January 2012 to December 2021 in the Gastrointestinal Cancer Center in the Beijing Cancer Hospital were analyzed. According to the operation method, the patients were divided into total laparoscopic group and laparoscopic-assisted group. Variables studied comprised: (1) surgical procedure and postoperative recovery; (2) postoperative pathological findings; and (3) postoperative complications. Measurement data with skewed distribution are represented as mean(quartile 1, quartile 3). Comparisons between groups were evaluated using the Mann-Whitney U test. Results: After propensity score matching in a 1:1 ratio, there were 40 patients in the total laparoscopic distal gastrectomy group and 40 in the laparoscopic-assisted distal gastrectomy group. Baseline characteristics did not differ significantly between the two groups (all P>0.05).Compared with the laparoscopic-assisted group, the total laparoscopic group had shorter main incisions (4.1±1.0 cm vs. 8.5±2.8 cm, t=9.375, P<0.001), time to fluid intake [4.0 (3.0, 4.8) days vs. 5.0 (4.0, 6.0) days, Z=2.167, P=0.030], and duration of indwelling abdominal drainage catheter [6.0 (6.0, 7.0) days vs. 7.0 (6.0, 8.0) days, Z=2.323, P=0.020]. Numerical Rating Scale scores on postoperative days 1 and 2 were higher in the total laparoscopic than the laparoscopic-assisted group [2.5 (1.0, 3.0) vs. 1.5 (1.0, 2.0), Z=1.980, P=0.048; 2.0 (1.0, 3.0) vs. 1.0 (1.0, 2.0), Z=2.334, P=0.020, respectively]. However, there were no significant differences between the groups in operation time, intraoperative blood loss, white blood cell count, hemoglobin concentration, or albumin concentration on postoperative day 1, time to ambulation, mean time to bowel movement, postoperative admission to the intensive care unit, length of postoperative hospital stay, or Numerical Rating Scale scores on postoperative day 3 (all P>0.05). There were also no significant differences between the two groups in maximum tumor diameter, pathological tumor type, total number of lymph nodes dissected, or total number of positive lymph nodes (all P>0.05). The incidence of postoperative complications was 15.0% (6/40) in the total laparoscopic group and the laparoscopic-assisted group; these differences are not significant (χ²<0.001, P>0.999). Conclusions: Compared with laparoscopic-assisted radical gastrectomy for distal gastric cancer, total laparoscopic surgery has the advantages of shorter incision, shorter time to fluid intake, and shorter duration of indwelling abdominal drainage catheter in older patients (age ≥65 years). Total laparoscopic radical gastrectomy for distal gastric cancer does not increase the risk of postoperative complications and could therefore be performed more frequently.
Aged ; Humans ; Gastrectomy/methods* ; Laparoscopy/methods* ; Postoperative Complications ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Surgical Wound ; Treatment Outcome

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q₁, Q₃) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
Male ; Humans ; Middle Aged ; Aged ; Adult ; Female ; Beijing ; Follow-Up Studies ; Herpes Zoster/epidemiology* ; Pain/epidemiology* ; Exanthema

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q₁, Q₃) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
Male ; Humans ; Middle Aged ; Aged ; Adult ; Female ; Beijing ; Follow-Up Studies ; Herpes Zoster/epidemiology* ; Pain/epidemiology* ; Exanthema

OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Apoptosis ; Benzothiazoles ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Paclitaxel/therapeutic use* ; Phenylurea Compounds ; RNA, Messenger ; STAT5 Transcription Factor/pharmacology* ; Signal Transduction ; fms-Like Tyrosine Kinase 3