AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

Objective    To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods    The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results    A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion    The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.

OBJECTIVE: To observe the acute toxic reaction of the Li-Dan-He-Ji granules, and to evaluate its safety. METHODS: Sixty C57BL6/J mice were randomly divided into normal control group, vehicle group and drug treatment group, with 10 females and 10 males in each group. According to the Technical guidelines for the study of toxicity of single drug administration, the maximum administration dosage (MAD) was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g (42.8 g/kg), three times within 24 hours, with an interval of 6 hours. The vehicle group was fed with the same pure water. The normal control group received no treatment. The mice were observed continuously for 14 days, and the appearance characteristics, behavioral activities, body weight changes and the number of deaths in each group were recorded. At the 14 days, blood samples were collected from the eyeballs, and routine blood tests such as white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), lymphocyte percentage (LYM%), neutrophil percentage (NEU%), red blood cell count (RBC), hemoglobin (Hb), and platelet count (PLT) were performed. And alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and other biochemical indicators. The mice were then sacrificed, and the histopathological changes of liver and kidney were observed by hematoxylin-eosin (HE) staining. The organ indexes of heart, liver, spleen, lung, kidney and thymus were calculated. RESULTS: The median lethal dose (LD₅₀) of Li-Dan-He-Ji granules were not obtained. During the MAD experiment, the animals in each group did not die, their behavioral activities were normal, and there was no significant change in liver and kidney histopathological examination. There were no significant differences in body weight, blood routine, biochemical indexes and organ index among all groups (all P > 0.05). The body weight (g) of normal control female and male group, vehicle female and male group and drug female and male group before administration were 18.96±1.14, 19.65±1.45, 19.33±1.30, 19.53±1.22, 19.28±1.69 and 19.48±1.28; 14 days after administration were 27.69±0.81, 28.19±2.22, 27.77±1.00, 27.88±1.85, 27.92±1.33 and 28.07±1.93, respectively. CONCLUSIONS The Li-Dan-He-Ji granules have low oral toxicity, combined with clinical observation, can be safely used in infants.
Animals ; Female ; Humans ; Male ; Mice ; Body Weight ; Kidney ; Leukocyte Count ; Liver ; Toxicity Tests, Acute

Objective:To explore the related factors affecting the prognosis of children with parenteral nutrition-associated cholestasis (PNAC).Methods:Twenty children with PNAC admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were selected as research objects by retrospective study. According to prognosis, children were divided into good (15 cases) and poor prognosis group (5 cases). Clinical data such as general condition, intravenous nutrition duration, related biochemical examination indexes and main treatment methods of children in the two groups were collected. Spearman correlation analysis was used to quantify the correlation between alanine aminotransferase (ALT) and poor prognosis. Univariate analysis was used to analyze the risk factors affecting the prognosis of children with PNAC, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALT on the prognosis of children.Results:There were no significant differences in gender, body weight, gestational age, age, feeding mode, duration of intravenous nutrition, direct bilirubin (DBil), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), total protein (TP), serum albumin (Alb), globulin (GLB), alkaline phosphatase (ALP), platelet count (PLT), white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), lymphocyte count (LYM), urine culture, AST/PLT ratio (APRI) and main treatment methods between the two groups. Total bilirubin (TBil), ALT, neutrophil count (NEU) and monocyte count (MONO) in the good prognosis group were significantly lower than those in the poor prognosis group [TBil (μmol/L): 120.00±48.63 vs. 175.26±29.14, ALT (U/L): 73.25±44.29 vs. 145.30±74.33, NEU (×10 9/L): 2.55±1.29 vs. 5.08±4.10, MONO (×10 9/L): 1.23±0.87 vs. 2.13±0.60, all P < 0.05]. Logistic regression analysis showed that ALT was the risk factor affecting the prognosis of children with PNAC, when ALT increased by 1 U/L, the probability of poor prognosis increased by 3.6% [odds ratio ( OR) = 1.04, 95% confidence interval (95% CI) was 1.00-1.07, P = 0.04]. Spearman correlation analysis showed that the incidence of poor prognosis was positively correlated with ALT ( r = 0.49, P = 0.03). ROC analysis showed that ALT had certain predictive value for the prognosis of children with PNAC [area under ROC cure (AUC) = 0.83, 95% CI was 0.00-1.00, P = 0.03]; when the cut-off value was 121.50 U/L, its sensitivity was 80% and specificity was 93%, suggesting that ALT could be used as the main indicator for clinical prediction of poor prognosis for PNAC. Conclusion:ALT is an independent risk factor of poor prognosis in children with PNAC.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a risk of developing non-alcoholic hepatitis, cirrhosis and liver cancer. Postmenopausal women have an increased risk of developing metabolic diseases including NAFLD under the influence of various factors such as aging, endocrine and metabolic changes. This article summarizes the latest research of NAFLD in postmenopausal women to elaborate and analyze the epidemiological characteristics, correlation between NAFLD and postmenopause, possible pathogenesis as well as feasible prevention and treatment methods.

Objective: To evaluate the relationship between bolus volume and hyoid displacement in dysphagia patients with nasopharyngeal carcinoma after radiation therapy. Methods: Twenty-three nasopharyngeal carcinoma patients with dysphagia were recruited and their swallowing of 3, 5, 10 and 20ml of liquid food was studied fluoroscopically. The vertical and horizontal displacement of the hyoid as well as its time in motion were measured, and the relationship between the bolus volume, hyoid displacement and time in motion time was evaluated. Results: The largest vertical displacement of the hyoid (1.01±0.65cm) was observed when swallowing a 10ml bolus. The hyoid showed the smallest average horizontal displacement (0.39±0.34cm), when swallowing a 3ml bolus. The average motion time of the hyoid was (2.11±0.65) seconds. It was shorter when swallowing a 10 or 20ml bolus than when dealing with a smaller one. Hyoid motion time was negatively correlated with the horizontal displacement of the hyoid bone, and the volume of a swallow was negatively correlated with the hyoid motion time but positively correlated with the penetration-aspiration scale score. Conclusion Bolus volume affects hyoid displacement and hyoid motion time in nasopharyngeal carcinoma patients with dysphagia after radiation therapy. For patients with a penetration-aspiration scale score of 5 or less, the optimum bolus volume is 5 to 10ml.

Objective To observe the influences on prognoses and airway acid and base levels while using anti-inflammatory and anti-reflux therapies combined with "Hezhong Fuzheng massage" for treatment of infants with gastric volvulus (GV) and gastroesophageal reflux (GER)-induced pneumonia in order to provide evidence for clinical diagnosis and treatment of such infant disease. Methods Sixty infants 1-6 months old admitted to the Department of Integrated Traditional Chinese and Western Medicine of Wuhan Children's Hospital from January 2013 to December 2015 were diagnosed as pneumonia combined with GV and GER by the chest radiograph and radiography of upper gastrointestinal tract (UGT) with iodine, and according to difference in diagnostic methods, they were divided into an observation 1 group (30 cases) and an observation 2 group (30 cases). In observation 1 group, 24-hour pH value in upper digestive tract especially the distal esophagus was dynamically monitored, while in observation 2 group, 24-hour multichannel intraluminal impedance (MII) combined with pH monitoring of esophagus was carried out. Furthermore, two control groups were set up, each 30 cases; after radiography of the UGT with iodine, the control 1 group was diagnosed as GV and GER without pneumonia and control 2 group was diagnosed as only simple GV. Treatment of infant pneumonia was carried out in accordance with the guidelines for the management of community-acquired pneumonia in children; the treatment of GV and GER included postural, dietary, prokinetic and Hezhong Fuzheng massage [acupoint selection and massage was undertaken in 5 steps: push from the palmar crease to Banmen (rectilinear pushing manipulation) 300 times, push abdominal Yin and Yang (finger-pushing massage) 200 times, palpate the abdomen (clockwise) 100 times, poking of Tianshu 100 times, poke alternately bilateral Zusanli 100 times. Once-daily massage, (15±2) minutes each time, for consecutive 7 days]. The results of pH monitoring of the distal esophagus in observation 1 group was recorded; All GER data concerning pH monitoring of observation 2 group and the results of esophagus multi-channel intra-luminal impedance combined with pH monitoring in control group were compared. After 7 days of continuous treatment, the clinical efficacy of pneumonia and GV, hospitalization time, prognosis and the changes of sputum pH before and after treatment in the two observation groups were compared. Results In two observation groups, the main type of 60 cases with GV was organoaxial volvulus, accounting for 91.67% (55 cases), and more than 60% patients exhibited sputum pH <7.0. The distal esophagus 24-hour pH dynamic monitoring in observation 1 group showed that there were 26 cases with acid reflux (86.67%), 4 cases with GER negative (13.33%), the proportion of pH < 4 in GER negative patients was significantly lower than that in moderate acid reflux patients [3.35% (0.77% - 8.08%) vs. 26.23% (15.19% - 42.87%), P < 0.05], the number of long reflux (> 5 minutes) in GER negative patients was significantly reduced than that in mild acid reflux patients [times: 2 (0-5) vs. 7 (2-15), P < 0.05], the longest time of reflux in GER negative patients was significantly shorter than that in either mild or moderate acid reflux patients [minutes: 5.9 (2.5-10.0) vs. 19.2 (5.9-51.0), 41.6 (16.9-121.0), both P < 0.05]. The 24-hour MII-pH monitoring of esophagus in observation 2 group showed that there were 30 cases with pathological reflux, mainly mild acid reflux accounting for 90%, in which the percentage of proximal reflux events was 46.07% in the total reflux events. The numbers of acid reflux and proximal reflux in the observation 2 group were significantly higher than those in the control 1 and 2 groups [1 305 (37.72%) vs. 795 (25.69%) and 136 (18.89%), 1 594 (46.07%) vs. 687 (22.20%) and 154 (21.39%), both P < 0.05]; there were no significant differences in total effective rate (100% vs. 100%, P > 0.05) and hospitalization time (days: 7.58±1.09 vs. 7.67±1.12, P > 0.05) between the two observation groups. Conclusions For the diagnosis of infant pneumonia combined with GV and GER, the first selection of chest radiograph and radiography of the UGT with iodine can identify the severity of pneumonia, whether it is complicated with GV and its classification, and whether GER exists at the same time. The estimation of 24-hour pH dynamic monitoring of the acid reflux in the upper digestive tract especially the distal esophagus is consistent with that of the 24-hour MII-PH monitoring of esophagus. Moreover, 24-hour MII-PH monitoring of esophagus can also identify non-acid reflux, resulting in the GER diagnosis more accurate. Since the proximal reflux ratio of infants with GV combined with GER and pneumonia is relatively high and easy to cause cough and aspiration. attention should be paid on early diagnosis and timely intervention to such patients. The sputum acidity test can reflect the airway acid-base level and its manipulation is simple, so by that the real time disease situation can be estimated, and aspiration of sputum also can help the treatment. The therapeutic schedule formulated by our group can elevate the therapeutic effect, improve the airway acid-base environment and benefit prognosis.

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size (P=0.026) and histology differentiation type (P=0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ (P=0.000) or Ⅲ (P=0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors (P<0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

Objective To observe the clinical characteristics of infants with pertussis syndrome and the influence of gastroesophageal reflux (GER) on pertussis syndrome in small infants, and provide experience for improving curative effect. Methods ① The clinical data of 807 infants with pertussis syndrome treated at Wuhan Children's Hospital from January 2015 to June 2017 were retrospectively analyzed, in which their clinical characteristics including symptoms, signs and related physical and chemical examinations were summarized. ② Prospective randomized controlled trials were performed at the Children's Hospital of Wuhan from June 2017 to June 2018, there were 120 infants with ages < 6 months diagnosed as pertussis syndrome and simultaneously accompanied by gastric volvulus (GV) and GER, and they were randomly divided into a study group and a control group according to the date sequence of definite diagnosis, 60 cases in each group. The control group was given conventional medical treatment, while in the study group, additionally the infants received massage to restore gastric proper position and anti-reflux therapy. The clinical efficacies of two groups were observed. Results ① Retrospective analysis showed that clinically, pertussis syndrome commonly occurred in infants of ages < 6 months, accounting for 88.30% (713 cases); all cases had spastic cough, and 60.00% (484 cases) infants' coughing was severer at night. In laboratory examinations, 83.27% (672 cases) of the infants had elevated platelets (PLT), 25.03% (202 cases) had abnormal myocardial zymograms, and 70.38% (568 cases) had elevated white blood cells (WBC). In the pathogen examination, only were pathogens found in 34.8% infants, mainly single pathogen infection, accounting for 86.12%. Chest radiographs suggested 71.50% of infants with pneumonia, and 73.00% of infants with GER, among which 77.92% of infants were accompanied by GV. ② The prospective study showed that in the treatment of infants with pertussis syndrome accompanied by GV and GER, manual massage should be used timely to correct GV and simultaneously anti-reflux therapy should be given, in the aspects of time required to improve cough symptoms (days: 5.36±1.40 vs. 6.59±1.56, P < 0.01) and shortening of the hospital stay (days: 6.50±1.41 vs. 8.09±1.63, P < 0.01) in the study group were superior to those in the control group; the case of respiratory failure in the study group was lower than that in the control group [2 cases vs. 8 cases, P < 0.05]. Conclusions In pertussis syndrome, lymphocytes occupy the main proportion of WBC elevation that is an important differential criterion between pertussis syndrome and infantile pneumonia with gastric volvulus and gastroesophageal reflux. PLT elevation in pertussis syndrome suggests that attention should be paid to the elevation as that might be related to the disease prognosis. It is necessary to further investigate whether the positive pathogen discovered in the course of pertussis syndrome is a pathogenic one, and attention should also be paid to the medical examination of GV and GER in the small infants with pertussis syndrome, since early proper intervention to correct GV and GER can significantly improve their clinical efficacies.