Aim To observe the effect of betulinic acid (BA) on the migration and invasion of human gastric cancer MKN-45 cells induced by transforming growth factor-pi (TGF-β1), and to explore the effect of BA on epithelial-mesenchymal transition (EMT) and the potential mechanism. Methods The MKN-45 cells were cultivated in vitro, and the effects of different concentrations of BA on the proliferation of MKN-45 cells at 24, 48 and 72 h were detected using CCK-8 method. The effects of BA (5, 10, 20 jjunol • L) and TGF-01 inhibitor LY2109761 (10 ^mol • L"

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

OBJECTIVE: To compare the effects of different concentrations of linolenin on inhibiting apoptosis of chondrocytes in the growth plate, and to screen the optimal concentration of linolenin, so as to provide theoretical support for delaying epiphyseal closure and promoting long bone growth in rats. METHODS: Two 4-week-old male SD rats (SPF grade) with a body mass of 80 g were selected. The growth plate cartilage of rat tibia and femur was dissected and isolated in vitro to obtain growth plate chondrocytes for culture. The chondrocytes were observed and identified by inverted phase contrast microscope and typeⅡ collagen immunofluorescence test, and then 20 ng/ml IL-1β was used to induce apoptosis of growth plate chondrocytes as model group, and added with 1, 10, 20, 40 μM linolenin as the experimental group, and 5 μM letrozole as the positive control group. The cells were cultured for 24 and 48 hours respectively. The drug promoted cell proliferation was observed by MTT method, and the drug inhibited cell apoptosis was detected by flow cytometry. RESULTS: Contents 1, 10, 20, 40 μM could promote cell proliferation in varying degrees, and the principle was that the drug inhibits IL-1β induced chondrocyte apoptosis in the growth plate, and the optimal concentration of drugs to inhibit apoptosis was 20 μM. CONCLUSION The appropriate concentration of linseed lignans can significantly inhibit the apoptosis of chondrocytes in the growth plate of rats, and the optimal drug concentration is 20 μM. It provides possibility for delayed bone closure and longer growth time to promote bone growth during development.
Male ; Rats ; Animals ; Growth Plate ; Chondrocytes ; Flax ; Rats, Sprague-Dawley ; Apoptosis ; Lignans/pharmacology*

OBJECTIVES: To systematically evaluate the risk factors for necrotizing enterocolitis (NEC) in preterm infants. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data were searched for case-control studies and cohort studies on the risk factors for NEC in preterm infants published up to December 2021. RevMan 5.3 software was used to perform the Meta analysis. RESULTS: A total of 38 studies were included (28 case-control studies and 10 cohort studies). The Meta analysis showed that maternal gestational diabetes (OR=2.96, P<0.001), intrahepatic cholestasis during pregnancy (OR=2.53, P<0.001), preeclampsia (OR=1.73, P=0.020), history of neonatal asphyxia (OR=2.13, P<0.001), low gestational age (OR=1.23, P=0.010), sepsis (OR=5.32, P<0.001), patent ductus arteriosus (OR=1.57, P=0.001), congenital heart disease (OR=3.78, P<0.001), mechanical ventilation (OR=2.23, P=0.020), history of antibiotic use (OR=1.07, P<0.001), use of vasopressors (OR=2.34, P=0.040), and fasting (OR=1.08, P<0.001) were risk factors for NEC in preterm infants, while cesarean section (OR=0.73, P=0.004), use of pulmonary surfactant (OR=0.43, P=0.008), and breastfeeding (OR=0.24, P=0.020) were protective factors against NEC. CONCLUSIONS Maternal gestational diabetes, intrahepatic cholestasis during pregnancy, preeclampsia, low gestational age, fasting, sepsis, patent ductus arteriosus, congenital heart disease, and histories of asphyxia, mechanical ventilation, antibiotic use, and use of vasopressors may increase the risk of NEC in preterm infants, while cesarean section, use of pulmonary surfactant, and breastfeeding may decrease the risk of NEC in preterm infants.
Anti-Bacterial Agents ; Asphyxia ; Cesarean Section ; Cholestasis, Intrahepatic ; Diabetes, Gestational ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Pre-Eclampsia ; Pregnancy ; Pulmonary Surfactants ; Risk Factors ; Sepsis

Jichuanjian， from the Jing Yue’s Collected Works by Zhang Jingyue， a famous doctor of Ming Dynasty， is composed of Angelica， Achyranthes bidentata， Cistanche deserticola， Alismatis Rhizoma， Shengma and Fructus Aurantii. It is one of the first 100 classic prescriptions published by the National Administration of Traditional Chinese Medicine. The original book states that where the disease is related to deficiency， with impacted stool， medicines such as Xiaohuang prescription cannot be used. If the treatment is needed， Jichuanjian should be applied. Through the textual research of ancient and modern literature， it is found that the efficacy of Jichuanjian has changed from ancient to modern times. In the medical books of the Ming and Qing Dynasties and the modern ones， the treatment is mostly carried out based on the constipation due to deficiency recorded in the original book， while in contemporary times， the treatment of Jichuanjian focuses on kidney （yang）-deficiency constipation and yin-deficiency constipation. Especially since modern times， Jichuanjian is frequently used to treat kidney-deficiency constipation according to the description in the planning textbooks of traditional Chinese medicine colleges and universities， which causes doubts among the authors. To actively respond to the call of General Secretary Xi Jinping that we should strengthen the sorting and excavation of the essence of classical medical books， this paper analyzed and demonstrated the original text and the drug composition， traceability and application by future generations of Jichuanjian based on the Jing Yue’s Collected Works. It was concluded that Jichuanjian was prepared for the treatment of constipation due to weak constitution， fluid deficiency， and emergent purgation， aiming for constipation due to weak constitution and fluid consumption rather than kidney-deficiency constipation described in modern textbooks. As Jichuanjian was developed for similar syndromes， it was reasonable that it was understood by later generations of doctors from the perspective of liver and kidney as well as earth dampness and wood stagnation， which however remains to be further explored and verified in clinic. By combing and discussing the efficacy of Jichuanjian， this paper could provide theoretical basis for the clinical application and modern development of Jichuanjian.

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ²=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ²=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.
Allergens ; Animals ; Cats ; Cesarean Section ; Dander ; Dogs ; Female ; Horses ; Immunoglobulin E ; Male ; Pregnancy ; Rhinitis, Allergic

Objectives: To examine the landscape and metastases of the lymph nodes in prostatic anterior fat pad (PAFP) at radical prostatectomy (RP), and to describe the clinical characteristic of the patients with lymph node metastases in PAFP. Methods: The clinical and pathological data of 287 prostate cancer patients underwent RP from December 2019 to August 2021 in Department of Urology, Sun Yat-sen University Cancer Center were collected and analyzed retrospectively. All patients were male, aging (66±7) years (range: 42 to 83 years). The preoperative prostate-specific antigen (PSA) (M(IQR)) were 16.00(29.64) μg/L (range: 0.01 to 99.90 μg/L). There were 244 patients with localized or locally advanced prostate cancer and 43 patients with metastatic prostate cancer. All PAFP were dissected at RP routinely and were sent for pathologic analysis respectively. The PAFP was dissected from the prostate apex caudally toward the bladder neck and dissection extended to the joint of the prostate and the endopelvic fascia bilaterally. All the specimen of PAFP were examined and reported by subspecialty pathologists of genitourinary tumors. Statistical analysis was performed by Student t test, Wilcoxon rank-sum test, χ² test or Fisher exact test. Results: There were 8.0% (23/287) patients with lymph nodes in PAFP, 3.8% (11/287) patients with PAFP lymph node metastases. Pathologically upstaged occurred in 1 patient due to the PAFP lymph node as the solitary metastatic lesion. Patients with lymph node metastases in PAFP presented higher preoperative PSA (M(IQR): 48.2(73.0) μg/L vs. 15.4(26.5) μg/L, Z=3.158, P=0.002), clinical T stage and N stage (Z=2.977, P=0.003; Z=2.780, P=0.005) and preoperative Gleason score (Z=2.205, P=0.027). Conclusions: Routine dissection of PAFP at RP and separately pathological analysis may allow more lymph nodes and lymph node metastases detection. More accurate pathological N stage may be acquired and consequently may improve the survival of patients by offering more appropriate adjuvant or salvage therapy.
Humans ; Male ; Prostate/pathology* ; Lymphatic Metastasis/pathology* ; Prostate-Specific Antigen ; Retrospective Studies ; Prostatectomy ; Lymph Nodes/pathology* ; Prostatic Neoplasms/therapy* ; Adipose Tissue ; Lymph Node Excision

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases