[Predictive factors for HBsAg-negative seroconversion in chronic hepatitis B after antiviral therapy].

Hepatitis B surface antigen (HBsAg) negative seroconversion (HBsAg < 0.05 IU/ml) is research hotspot in the field of hepatitis at this stage, and patients who achieve HBsAg negative seroconversion have significantly fewer liver-related complications. Presently, there are many studies with regard to HBsAg-negative seroconversion, but there are still relatively few indicators used in clinical practice to predict HBsAg-negative seroconversion. Low baseline HBsAg quantification and dynamic decline during treatment are currently recognized as the best indicators for predicting HBsAg-negative seroconversion. However, other factors such as viral genotype, elevated transaminases during treatment course, immune cell function and cytokine levels, and host factors can all influence HBsAg-negative seroconversion. This article reviews the relevant indicators and potential predictive factors for HBsAg-negative seroconversion.

[Cardio-metabolic risk and adverse pregnancy outcomes in the first trimester: findings from the Shenzhen birth cohort study].

Objective: To investigate the relationship between cardio-metabolic abnormalities in the first trimester and adverse pregnancy outcomes (APO). Methods: This cohort study recruited singleton pregnancies in the first trimester (6-13+6 weeks of gestation) from Shenzhen Maternal and Child Health Care Hospital between January 1, 2021, and October 31, 2022. Cardiometabolic markers, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were recorded during the first trimester. Incidence of APO, including gestational hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, fetal growth restriction, small for gestational age infant, and placental abruption, was documented. Cardiovascular metabolic abnormalities in the first trimester were defined as meeting one or more of the following criteria: elevated BMI (BMI≥24 kg/m²), elevated TG (TG≥1.7 mmol/L), decreased HDL-C (HDL-C<1.0 mmol/L), elevated blood pressure (systolic pressure≥130 mmHg (1 mmHg=0.133 kPa) and/or diastolic pressure≥85 mmHg), elevated FPG (FPG≥5.6 mmol/L). Enrolled women were categorized into abnormal cardio-metabolic and normal cardio-metabolic groups. Poisson regression was employed to analyze the association between cardio-metabolic abnormalities in the first trimester and APO. Results: The study included 14 197 pregnant women with an age of (32.0±4.1) years. There were 8 139 women in the normal cardio-metabolic group and 6 058 women in the abnormal cardio-metabolic group. Women with cardio-metabolic disorders in the first trimester had a younger gestational age and higher incidence rates of preterm birth, gestational hypertension, preeclampsia, and gestational diabetes mellitus (all P<0.05). In multivariable Poisson regression, elevated BMI (RR=1.22, 95%CI 1.15-1.29), elevated FPG (RR=1.59, 95%CI 1.38-1.82), elevated TG (RR=1.22, 95%CI 1.13-1.31), and elevated blood pressure (RR=1.50, 95%CI 1.39-1.63) were independent risk factors for APO, while decreased HDL-C (RR=0.93, 95%CI 0.70-1.23) was not. Elevated blood pressure (RR=5.57, 95%CI 4.58-6.78), elevated BMI (RR=1.71, 95%CI 1.40-2.09), and elevated TG (RR=1.38, 95%CI 1.10-1.74) had the greatest impact on the risk of developing preeclampsia. Elevated FPG (RR=1.70, 95%CI 1.45-1.99) had the greatest impact on the risk of gestational diabetes. Conclusions: Elevated blood pressure, BMI, TG and FPG in the first trimester are closely related to APO.

The expression of ferroptosis-related genes in osteoporosis based on GEO.

OBJECTIVE: The aim of this study was to screen the differential genes related to ferroptosis in osteoporosis patients. MATERIALS AND METHODS: GEO2R was used to screen the differential genes related to ferroptosis in osteoporosis patients by searching the relevant chips in the GEO database, and Spearman's correlation analysis was used to describe the correlation between quantitative variables without normal distribution. p-values lower than 0.05 were considered statistically significant. Another group of osteoporosis patients was selected in the GEO database to verify the significantly differentially expressed genes. RESULTS: The results showed that 10 samples in chip GSE35956 were identified as research objects, and a total of 5 ferroptosis differential genes were screened out: ATP5MC3, CDKN1A, MT1G, NCOA4, SLC1A5, of which 3 up-regulated genes (CDKN1A, MT1G, SLC1A5), 2 down-regulated genes (ATP5MC3, NCOA4). The above differential genes were placed in 19 samples of chip GSE35959 for verification, and the same expression trend was obtained, but only the MT1G difference was statistically significant. CONCLUSIONS: The gene correlation test found that MT1G and ATP5MC3 had a strong negative correlation.

Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

Claudin-10 Decrease in the Submandibular Gland Contributes to Xerostomia.

Tight junction proteins play a crucial role in paracellular transport in salivary gland epithelia. It is clear that severe xerostomia in patients with HELIX syndrome is caused by mutations in the claudin-10 gene. However, little is known about the expression pattern and role of claudin-10 in saliva secretion in physical and disease conditions. In the present study, we found that only claudin-10b transcript was expressed in human and mouse submandibular gland (SMG) tissues, and claudin-10 protein was dominantly distributed at the apicolateral membranes of acini in human, rat, and mouse SMGs. Overexpression of claudin-10 significantly reduced transepithelial electrical resistance and increased paracellular transport of dextran and Na+ in SMG-C6 cells. In C57BL/6 mice, pilocarpine stimulation promoted secretion and cation concentration in saliva in a dose-dependent increase. Assembly of claudin-10 to the most apicolateral portions in acini of SMGs was observed in the lower pilocarpine (1 mg/kg)-treated group, and this phenomenon was much obvious in the higher pilocarpine (10 mg/kg)-treated group. Furthermore, 7-, 14-, and 21-wk-old nonobese diabetic (NOD) and BALB/c mice were used to mimic the progression of hyposalivation in Sjögren syndrome. Intensity of claudin-10 protein was obviously lower in SMGs of 14- and 21-wk-old NOD mice compared with that of age-matched BALB/c mice. In the cultured mouse SMG tissues, interferon-γ (IFN-γ) downregulated claudin-10 expression. In claudin-10-overexpressed SMG-C6 cells, paracellular permeability was decreased. Furthermore, IFN-γ stimulation increased p-STAT1 level, whereas pretreatment with JAK/STAT1 antagonist significantly alleviated the IFN-γ-induced claudin-10 downregulation. These results indicate that claudin-10 functions as a pore-forming component in acinar epithelia of SMGs, assembly of claudin-10 is required for saliva secretion, and downregulation of claudin-10 induces hyposecretion. These findings may provide new clues to novel therapeutic targets on hyposalivation.

[Overview of design and construction of hypertensive disorders of a pregnancy-cohort in Shenzhen].

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.

[Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer].

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

[Preventive effect of atropine premedication on vagal reflex in patients undergoing suspension laryngoscopy during anesthesia induction].

Objective: To evaluate the preventive effect of atropine premedication during anesthesia induction on vagal reflex in patients undergoing suspension laryngoscopy. Methods: A total of 342 patients (202 males and 140 females) scheduled for suspension laryngoscopy under general anesthesia in Beijing Tongren Hospital from October 2021 to March 2022 were prospectively enrolled, with a mean age of (48.1±11.9) years. The patients were randomly divided into two groups using the random number table method: the treatment group (n=171) and the control group (n=171). Patients in the treatment group were administrated with 0.5 mg atropine intravenously guttae (ivgtt) while patients in the control group were given equivalent volume of normal saline. For all patients, if heart rate (HR)<50 beats/min happened during the insertion of the suspension laryngoscope, the operation should be stopped and the laryngoscope should be removed. Patients without HR recovery after the removal of the laryngoscope should be given 0.5 mg atropine, and the operation should be continued after the HR recovered. The primary outcome was the incidence of HR fluctuation over 20% (ΔHR>20%) before and immediately after suspension laryngoscope fixation, and the secondary outcomes included HR, mean arterial pressure (MAP) of the two groups recorded before and after anesthesia induction, before and immediately after suspension laryngoscope fixation, and the incidences of sinus bradycardia, laryngoscope removal and atropine treatment during operation. Results: The incidences of ΔHR>20% and bradycardia immediately after the suspension laryngoscope fixation were 14.6% (25/171) and 12.9% (22/171) in the treatment group, which were significantly lower than those in the control group [28.1% (48/171) and 29.8% (51/171)] (both P<0.05). The HR immediately after the suspension laryngoscope fixation in the treatment group [(66.4±13.5) beats/min] and in the control group [(60.8±15.7) beats/min] was significantly lower than those before the suspension laryngoscope fixation [(74.7±11.1) beats/min and (67.6±12.8) beats/min, respectively] (both P<0.05). There were no significant differences in MAP between the two groups at each time point (all P>0.05). The incidence of laryngoscope removal once plus 0.5 mg atropine administration, laryngoscope removal twice plus 0.5 mg atropine administration and laryngoscope removal twice plus 1.0 mg atropine administration was 9.9% (17/171), 1.8% (3/171) and 0 (0) in the treatment group, respectively, which was significantly lower than those in the control group [24.0% (41/171), 5.8% (10/171) and 2.3% (4/171), respectively] (all P<0.05). Conclusion: Atropine premedication during anesthesia induction can effectively reduce the occurrence of vagal reflex in patients undergoing suspension laryngoscopy.

Screening and bioinformatics analysis of senile osteoporosis genes based on GEO database.

OBJECTIVE: Despite improvements in research on osteoporosis in the elderly, the specific mechanism remains unknown. In order to develop better treatment regimens with better efficacy and fewer adverse reactions (ARs), it is vital to unravel the pathogenesis of osteoporosis in the elderly. The GEO chip was used to screen differential genes in senile osteoporosis and analyze their interaction mechanisms in order to obtain potential therapeutic pathways and targets. MATERIALS AND METHODS: GSE35956 was downloaded from GEO database and used as the research object for KEGG pathway enrichment analysis, GO enrichment analysis and protein-protein interaction (PPI) network analysis, respectively, to explore the related mechanisms of the occurrence and development of osteoporosis in the elderly. RESULTS: There were 156 differentially expressed genes in the elderly (72 years old) and middle-aged (42 years old) diagnosed with osteoporosis, of which 6 were up-regulated and 150 were down-regulated. An analysis of gene enrichment using GO (gene body) revealed that differentially expressed genes (DEG) were mainly distributed in extracellular matrix (ECM) and other cell structures. Its functions include ossification, parathyroid hormone metabolism, multicellular biological signaling pathway, vitamin catabolism, interleukisn-5 metabolism, transmembrane transporter activity, receptor signaling pathway, calcium metabolism and other molecular functions. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), an online resource, signaling pathways associated with age-related osteoporosis (OP) are significantly enriched. The DEG enrichment pathways include Wnt, ECM-receptor interaction, cGMP-PKG, GAG degradation, and calcium signaling. A protein and protein interaction (PPI) network was constructed for 14 key genes, including CD44, GRIA1, KNG1 and IL7R. CONCLUSIONS: The findings of this study indicate that CD44, GRIA1, KNG1, IL7R, and other differential genes affect the Wnt signaling pathway in the elderly, which can provide new targets for the follow-up basic research and treatment of osteoporosis in the elderly.

The Role of Endothelial Barrier Function in the Fibrosis of Salivary Gland.

In the salivary glands, fibrosis occurs in many pathological conditions. Endothelial tight junction (TJ)-based barrier function plays a vital role in maintaining the homeostasis of the salivary glands. However, whether endothelial barrier function is changed and involved in the pathogenesis of glandular fibrosis is unknown. Here, by using a mouse model in which the main excretory duct of the submandibular gland (SMG) was ligated to induce inflammation and fibrosis, endothelial barrier function and TJ protein expression and distribution were examined. Both 4-kDa and 70-kDa fluorescence-labeled dextrans permeated more in the 1-, 3-, and 7-d ligated SMGs. Meanwhile, the mRNA level of claudin-5 was increased with an obvious redistribution from apicolateral membranes to lateral membranes and cytoplasm in the fibrotic glands. Notably, the TJ sealer AT1001 significantly attenuated the disrupted endothelial barrier function and thereby ameliorated the glandular fibrosis. Cytokine array detection showed that monocyte chemoattractant protein-1 (MCP-1) was highly enriched in the 3-d ligated SMGs, and MCP-1 directly impaired barrier function, increased claudin-5 expression, induced the relocalization of claudin-5, and activated p-ERK1/2 in cultured human endothelial cells. Furthermore, the upregulation and disorganization of claudin-5 as well as the elevation of MCP-1 and p-ERK1/2 signaling were also confirmed in fibrotic SMGs from patients with chronic sialadenitis and immunoglobulin G4-related sialadenitis. Altogether, our findings revealed that disrupted endothelial barrier function contributed to the progression of glandular fibrosis, and targeting endothelial TJs might be a promising approach to alleviate salivary gland fibrosis-related diseases.

The subfamily Xerocomoideae (Boletaceae, Boletales) in China.

Xerocomoideae is an ecologically and economically important Boletaceae subfamily (Boletales) comprising 10 genera. Although many studies have focused on Xerocomoideae in China, the diversity, taxonomy and molecular phylogeny still remained incompletely understood. In the present study, taxonomic and phylogenetic studies on Chinese species of Xerocomoideae were carried out by morphological examinations and molecular phylogenetic analyses. Eight genera in Xerocomoideae, viz. Aureoboletus, Boletellus, Heimioporus, Hemileccinum, Hourangia, Phylloporus, Pulchroboletus, and Xerocomus were confirmed to be distributed in China; 97 species of the subfamily were accepted as being distributed in China; one ambiguous taxon was tentatively named Bol. aff. putuoensis; two synonyms, viz. A. marroninus and P. dimorphus were defined. Among the Chinese accepted species, 13 were newly described, viz. A. albipes, A. conicus, A. ornatipes, Bol. erythrolepis, Bol. rubidus, Bol. sinochrysenteroides, Bol. subglobosus, Bol. zenghuoxingii, H. squamipes, P. hainanensis, Pul. erubescens, X. albotomentosus, and X. fuscatus, 36 known species were redescribed, and the other 48 species were reviewed. Keys to accepted species of Aureoboletus, Boletellus, Heimioporus, Hemileccinum, Hourangia, Phylloporus, and Xerocomus in China were also provided. Taxonomic novelties: New species: Aureoboletus albipes N.K. Zeng, Xu Zhang & Zhi Q. Liang, A. conicus N.K. Zeng, Xu Zhang & Zhi Q. Liang, A. ornatipes N.K. Zeng, Xu Zhang & Zhi Q. Liang, Boletellus erythrolepis N.K. Zeng, R. Xue, S. Jiang & Zhi Q. Liang, Bol. rubidus N.K. Zeng, R. Xue, Y.J. Hao & Zhi Q. Liang, Bol. sinochrysenteroides N.K. Zeng, R. Xue & Kuan Zhao, Bol. subglobosus N.K. Zeng, R. Xue, S. Jiang & Zhi Q. Liang, Bol. zenghuoxingii N.K. Zeng, R. Xue, S. Jiang & Zhi Q. Liang, Hemileccinum squamipes N.K. Zeng, Chang Xu & Zhi Q. Liang, Phylloporus hainanensis N.K. Zeng, L.L. Wu, & Zhi Q. Liang, Pulchroboletus erubescens N.K. Zeng, Chang Xu & Zhi Q. Liang, Xerocomus albotomentosus N.K. Zeng, H.J. Xie, Chang Xu & Zhi Q. Liang, and X. fuscatus N.K. Zeng, H.J. Xie, Chang Xu & Zhi Q. Liang. Citation: Xue R, Zhang X, Xu C, Xie HJ, Wu LL, Wang Y, Tang LP, Hao YJ, Zhao K, Jiang S, Li Y, Yang YY, Li Z, Liang ZQ, Zeng NK (2023). The subfamily Xerocomoideae (Boletaceae, Boletales) in China. Studies in Mycology 106: 95-197. doi: 10.3114/sim.2022.106.03.

[Independent and combined effects of pre-pregnancy BMI and gestational diabetes on early adiposity rebound timing in children].

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.

[Effect of closed extension tube on preventing airway leakage during artificial airway clearance].

Objective: To explore the role of closed extension tube in preventing airway leakage during artificial airway clearance. Methods: The test lung was connected with a ventilator for mechanical ventilation. The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O(1 cmH2O=0.098 kPa), respectively. The circuit was connected with an open extension tube or a closed extension tube. The ventilator was set with different pressure parameters to observe the changes of airway pressure and tidal volume during airway clearance. Results: (1) The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O, and the airway pressures (in cmH2O) of circuit connected with open extension tube were (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12)and(35.65±0.31)/(9.72±0.07), respectively.Under the same ventilator pressure parameters, the airway pressures (in cmH2O) of circuit connected with close extension tube were (16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively. The airway pressure of circuit connected with open extension tube was lower than that connected with closed extension tube(P<0.05);with the increase of the pressure setting of the ventilator, the difference of the airway pressure between the two extended tubes gradually increased. When the maximum inspiratory pressure of the ventilator was set 36 cmH2O, the difference reached 1.69 cmH2O. (2) The airway pressures (in cmH2O) dropped from (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12), (35.65±0.31)/(9.72±0.07) to (13.42±0.4)/(3.15±0.14), (16.81±0.6)/(4.30±0.14), (20.22±0.5)/(5.48±0.45), (23.73±1.4)/(6.25±0.22), (24.78±0.7)/(7.13±0.21), (20.83±0.4)/(6.61±0.19)when the suction port of the open extension tube was opened (P<0.05);and the tidal volume (in L) also decreased from 0.328±0.004, 0.580±0.012, 0.621±0.003, 0.626±0.003, 0.615±0.003, 0.603±0.002 to 0.272±0.008, 0.416±0.051, 0.487±0.047, 0.396±0.116, 0.507±0.022, 0.508±0.079, respectively (P<0.05). The decrease of airway pressure and tidal volume gradually increased with the increase of ventilator setting pressure. When the ventilator setting parameter was 36/10 cmH2O, the decrease of airway inspiratory pressure was (14.82±0.51) cmH2O and the maximum reduction of tidal volume was (0.164±0.021)L. (3)The airway pressure (in cmH2O) was increased to(15.70±0.23)/(4.80±0.33), (19.01±0.81)/(5.71±0.34), (22.27±0.62)/(6.85±0.44), (25.35±2.09)/(7.94±0.16), (28.38±0.46)/(8.96±0.23), (33.34±0.71)/(9.71±0.25) when the suction tube was inserted from the suction port of the open extension tube in the open state, and the tidal volume (in L) was increased to 0.340±0.016, 0.563±0.020, 0.571±0.030, 0.556±0.026, 0.514±0.021, 0.512±0.031 as well.The airway pressure and tidal volume of the ventilation circuit were higher than those in the open state, but still lower than those in the closed state. Compared with the closed state of the suction port, the maximum pressure drop and tidal volume decrease were (3.53±0.46) cmH2O and (0.101±0.011) L, respectively. (4) The pressure of the ventilator was set between 16/5 cmH2O to 36/10 cmH2O. The airway pressure (in cmH2O) was decreased from (16.26±0.04)/(4.85±0.04), (20.74±0.15)/(6.42±0.11), (25.09±0.31)/(7.10±0.13), (29.38±0.24)/(8.17±0.09), (33.80±0.16)/(9.02±0.17), (37.89±0.19)/(9.83±0.07) to(16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively during the insertion of the suction tube from the suction port of the closed extension tube, and the tidal volume (in L) was decreased from0.361±0.005, 0.592±0.003, 0.631±0.001, 0.642±0.007, 0.633±0.007, 0.626±0.08 to 0.335±0.005, 0.588±0.008, 0.631±0.002, 0.638±0.004, 0.628±0.004, 0.618±0.005.The maximum pressure change of the ventilation circuit was (0.83±0.27) cm H2O and the maximum tidal volume change was (0.008±0.006)L. The changes of airway pressure and tidal volume were significantly lower than those of ventilation circuit connected with open extension tube under the same pressure parameters. Conclusion: The connection of closed extension tube in mechanical ventilation circuit can reduce the airway leakage during artificial airway clearance, which is worthy of clinical recommendation.

[Changes in the types and daily treatment costs of anti-glaucoma eye drops in China in recent 15 years].

Objective: To investigate the changes in the types of anti-glaucoma eye drops and daily treatment costs in 2021 compared with 2006 in China. Methods: The information of the main anti-glaucoma eye drops in 2021 was obtained from the database of Yaozhi.com. The daily cost of each eye drop was calculated by recording the number of drops in a single bottle and pricing in the national market, and the corresponding information of anti-glaucoma eye drops collected in 2006 was compared. Based on the income of Chinese residents in 2006 and 2021, the proportion of the daily cost of anti-glaucoma eye drops in the annual income of residents was analyzed. Results There were 32 kinds of anti-glaucoma eye drops in 2021, and the daily cost was 0.34 to 16.00 yuan. The daily cost is 0.34 to 6.77 yuan after removing the single-dose package. The number of drugs in 2021 was significantly higher than that in 2006 (16). In 2021, prostaglandins accounted for the highest proportion of 31.25%. There was a significant increase in the number of generic drugs, fixed formulations and preservative-free single-dose packages. In 2021, the price of imported drugs was significantly reduced, with the daily cost falling by 29.28% to 53.78% compared with 2006. In 2021, the daily cost of the most expensive drugs accounted for 12.32% and 30.85% of the daily income of urban and rural residents, respectively (5.21% and 13.05% after removing single-dose packaged drugs), which were significantly lower than 37.46% and 122.79% in 2006. Conclusions Compared with 2006, the variety of anti-glaucoma eye drops increased significantly in 2021, and the daily treatment cost and the proportion of daily income were significantly reduced.

[Establishment and application of new techniques for submandibular gland preservation].

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

The effect of BMP2/Smads pathway mediating platelet-rich fibrin on rat bone mesenchymal stem cells.

OBJECTIVE: We explored the influences on platelet-rich fibrin (PRF) to rat Bone Mesenchymal Stem Cells (BMSCs), as well as the role of bone morphogenetic protein 2 (BMP2)/maternal signal protein homolog (Smads) pathway. MATERIALS AND METHODS: The proposed research is approved by the ethics board of the Second Affiliated Hospital of Harbin Medical University. The BMSCs were isolated and purified. The BMSCs were assigned to a control group arbitrarily, PRF group, BMP activator group and BMP inhibitor group (hereinafter referred to as activator group and inhibitor group). Each group of BMSCs in the logarithmic growth phase was detected for the alkaline phosphatase (ALP) activity since 3 days and 14 days of culture; CCK-8 assay was conducted for detection of the proliferation of BMSCs; Real time PCR was conducted for detection of the osteogenic differentiation marker collagen I (COL-I), BMP2, Runt-related transcription factor 2(RUNX2), osteocalcin (OCN) mRNA relative expression levels; Western-Blot detection of BMP2, OCN, P-SMAD1/5/8, relative expression level of RUNX2 protein. RESULTS: In contrast to the control group, BMSCs' the ALP activity of the PRF group, activator group, as well as inhibitor group increased for 3 days and 14 days, and the activator group>PRF group>inhibitor group (p≤0.05). ALP activity in each group was elevated with the increase in culture time, the ALP activity of the control group, PRF group, activator group and inhibitor group increased (p≤0.05). In comparison to the control group, the relevant expression levels of COL-I, BMP-2, RUNX2 and OCN in the PRF group, activator group, and inhibitor group increased, and the activator group>PRF group>inhibitor group (p≤0.05). The relative expression levels of BMP2, OCN, p-SMAD1/5/8 and RUNX2 protein in each group were statistically different, the activator group>PRF group>control group>inhibitor group (p≤0.05). CONCLUSIONS: PRF can promote the proliferation and osteogenic differentiation of BMSCs by activating the BMP2/Smads signaling pathway.

[Effects of different eye protection methods during head and neck surgery under general anesthesia].

Objective: To compare the protective effects of vitamin A eye gel combined with 3M transparent tape and erythromycin eye ointment combined with 3M transparent tape on the eye surface during head and neck surgery under general anesthesia. Methods: From June to December 2021, a total of 120 patients undergoing elective head and neck surgery under general anesthesia in Beijing Tongren Hospital, Capital Medical University were enrolled. Each participant was randomly received vitamin A eye gel (vitamin A eye, n=60) or erythromycin eye ointment (erythromycin eye, n=60), followed by 3M transparent tape on one eye, and taping 3M transparent tape alone for the other eye. The hand-held slit lamp examination was performed 3 times at before induction of anesthesia, after resuscitation in the post anesthesia care unit (PACU) and 1 day after surgery. The primary outcome was corneal fluorescein sodium staining (CFS) score. Secondary outcomes included symptom assessment in dry eye (SANDE) questionnaire score, basic tear secretion test (Schirmer I test, SIt), break-up time (BUT) and incidence of adverse reactions. Results: Comparison within groups showed that CFS scores were significantly higher in vitamin A eyes and erythromycin eyes at PACU than before induction (P<0.05). Comparison between groups showed that CFS score at PACU in erythromycin eyes (0.62±0.16) was significantly higher than that in vitamin A eyes (0.13±0.01, P=0.007). Compared with before induction, SIt at PACU was significantly increased in the erythromycin eyes [(16.0±1.3) vs (11.4±4.9) mm, P=0.017],and was significantly decreased in vitamin A eyes [(10.2±3.6) vs (12.4±5.5) mm, P=0.046]. The BUT in PACU of erythromycin eyes, vitamin A eyes were (6.4±2.5) s, (6.8±2.1) s, respectively,and were significantly decreased compared with before induction (P<0.05). Comparison between groups showed that there was no significant difference in BUT and SANDE in PACU between two groups (P>0.05). For erythromycin eyes, discomfort symptoms in PACU included viscosity (66.7%, 40/60), conjunctival congestion (21.7%, 13/60), tingling (8.3%, 5/60), blurred vision (58.3%, 35/60). The incidence of these complications in vitamin A eye was 30.0% (18/60), 5.0% (3/60), 0 and 6.7% (4/60), respectively, and all the incidences were significantly higher than those of vitamin A eyes (all P<0.05). Conclusion: For patients undergoing head and neck surgery under general anesthesia, the combination of vitamin A ocular gel and 3M transparent tape is more effective in prevent postoperative ocular surface injury than the combination of erythromycin ointment and 3M transparent tape.

[Effect of ultrasound-guided serratus plane block combined with pectoral nerve block I on postoperative analgesia after radical mastectomy].

Objective: To study the effect of ultrasonic-guided serratus plane block combined with pectoral nerve block Ⅰ on postoperative analgesia after radical mastectomy. Methods: A total of 30 patients, all female, aged [M (Q1, Q3)] 53 (43, 62) years old, who underwent radical mastectomy in Beijing Tongren Hospital from May to August 2021 were selected. The patients were divided into two groups (n=15 in each group) using a random number table: general anesthesia alone+patient controlled intravenous analgesia (PCIA) group (control group) and serratus plane block combined with pectoral nerve block Ⅰ before general anesthesia+PCIA group (combined group). Numerical rating scale (NRS) at rest in both groups were detected in the post anesthesia care unit (PACU) and 4, 8, 12, 24, 36 and 48 h after operation. The time of first pain, the time of first pressing of the automatic analgesic device after the operation, the dosage of remifentanil during operation, cumulative dosages of sufentanil at 24 h and 48 h postoperatively, and the incidence of adverse effects were all recorded. Results: The NRS scores in combined group in the PACU and 4, 8, 12 and 24 h after surgery were (2.1±1.7), (1.7±1.5), (1.5±1.4), (1.5±1.3) and (1.7±1.3), respectively, while the NRS scores in control group at each time points were (4.5±2.0), (3.2±1.4), (2.7±0.9), (2.8±0.9) and (2.4±0.8), respectively, and the NRS scores in combined group were significantly lower than those in control group (all P<0.05). The NRS scores in combined group at 36 and 48 h after surgery were (1.8±1.6) and (1.6±1.2), while the NRS scores in control group were (2.2±0.9) and (2.1±0.8), and the differences between the two groups were not statistically significant (both P>0.05). The time of first pain and the time of the first pressing of the automatic analgesic device in combined group were (573±174) min and (962±313) min, which were significantly longer than those of control group [(13±6) min and (135±41) min] (both P<0.05). The dosage of remifentanil during operation and cumulative dosage of sufentanil at 24 h postoperatively in combined group were (410±129) µg and (14±4) µg, which were lower than those in control group [(580±225) µg and (21±11) µg] (both P<0.05). Cumulative dosage of sufentanil at 48 h postoperatively in combined group was (29±11) µg, while in control group was (36±14) µg, and the difference between the two groups was not statistically significant (P=0.131). The incidence of postoperative dizziness in combined group was 6.7% (1/15), which was lower than that of control group [40.0% (6/15)] (P=0.031). The incidence of nausea and pruritus was 6.7% (1/15) and 0 in combined group, while 20.0% (3/15) and 6.7% (1/15) in control group, with no statistical significance (both P>0.05). Conclusion: Serratus plane block combined with pectoral nerve block Ⅰ can effectively relieve postoperative pain, decrease the need for opioids, and reduce the incidence of adverse effects.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

[Comparison of the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery].

Objective: To compare the anesthetic effects of mivacurium and cisatracurium besylate in laser laryngeal microsurgery, and to provide clinical evidence and reference for further optimization of muscle relaxation application. Methods: From October 2021 to January 2022, fifty-six patients of Beijing Tongren Hospital, Capital Medical University, scheduled for laser laryngeal microsurgery with general anesthesia, were enrolled. These patients, aged 18-65 years old, 25 males and 31 females, were divided into two groups (n=28) by random number table method. Cisatracurium besylate group (group C): cisatracurium besylate was injected at 0.1 mg/kg. Normal saline was continuously infused during operation. Mivacurium group (group M):Mivacurium was injected at 0.25 mg/kg and continuously infused at 0.3 mg·kg-1·h-1 during operation.The intubation time, the extubation time, recovery index, Cooper's score, Cormack-Lehane grade, surgical condition grade, postoperative residual neuromuscular block and allergic related adverse events were compared between the two groups. Results: The intubation time and the extubation time of group M were (3.7±1.1) and (16.2±5.0) min, which were statistically significant shorter than those of group C (4.9±0.7) and (26.4±8.6) min (all P<0.05). The recovery indexes of the patients in group M and group C were (4.5±3.4) and (6.2±5.0) min. The Cooper's scores of the two groups were both 9(9, 9). The Cormack-Lehane grades of the two groups were all grade Ⅰ. The number of cases with good/excellent surgical condition grades in group M and group C were 5/23 and 0/28. There were no significant differences in recovery index, Cooper's score, Cormack-Lehane grades and surgical condition grades between the two groups (all P>0.05). The TOF ratio of group M in the post anesthesia care unit (PACU) was (95.7±2.6) %, which was significantly higher than (92.9±3.9) % of group C(P=0.015). There were no significant differences in MAP and HR between the two groups at different time points (all P>0.05). The incidence of skin flushing in group M and group C was 10.7% (3/28) and 0, and the difference was not statistically significant (P=0.074). There were no cases of severe hypotension, significantly elevated airway pressure or airway spasm in both groups. Conclusion: In laser laryngeal microsurgery, compared with cisatracurium besylate, mivacurium has shorter intubation time and extubation time, stable hemodynamics, no significant increase in allergic related adverse events. mivacurium is safe and effective.