Research Progress of Upadacitinib in the Treatment of Crohn’s Disease / 中山大学学报(医学科学版)

Crohn’s Disease （CD） is a destructive， relapsing and remitting chronic inflammatory bowel disease that usually progresses to irreversible intestinal structural and functional changes， such as intestinal lumen stenosis， fistula formation and perianal lesions， severely affecting the quality of life of patients. This review summarized the research progress on the mechanism， clinical application and safety of upadacitinib in the treatment of CD. Upadacitinib can increase the clinical remission and endoscopic response rates in patients with CD， improve the long-term outcome of CD patients and provide a new idea for the treatment of CD patients by using biological agents.

Exploration and practice of Peking University Model to improve the clinical teaching effect of clinical postgraduates majoring in periodontology / 中华口腔医学杂志

The number of patients with periodontal disease in China is large, and the ratio of doctors to patients is seriously imbalanced, especially in the insufficient number of periodontal specialists and periodontal teachers. Strengthening the cultivation of professional postgraduates in periodontology can effectively solve this problem. This paper summarizes the experiences of Peking University School and Hospital of Stomatology in the teaching of periodontal postgraduate students for more than 30 years, in cluding teaching objectives formulation, teaching resources allocation and enhancement of the quality control system of clinical teaching, for ensuring that the periodontal professional postgraduates could reach the expected level after training. This formed the current "Peking University Model". There are both opportunities and challenges in clinical teaching of periodontal postgraduates in domestic stomatology community. The authors hope that the continuous exploration and improvement of this teaching system will promote the vigorous development of clinical teaching for the postgraduates majoring in periodontology in China.

Outcome analysis of pregnancy termination and expectant treatment in pregnant women with suspected invasive placenta accreta spectrum disorders in the second trimester / 中华妇产科杂志

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.

The histopathological characteristics of peri-implantitis / 中华口腔医学杂志

Peri-implantitis (PI) has been defined as an inflammatory lesion of the mucosa surrounding an endosseous implant and with progressive loss of supporting peri-implant bones. In recent years, histopathological differences between PI and periodontitis of natural teeth had been described in animal experiments and a certain number of human experiments. In this paper, we review the histopathological differences between PI and periodontitis reported in the existing literature and try to find the differences in the occurrence and progression of these two diseases. Overall, inflammatory cell infiltrate (ICT) is more extensive in PI than in periodontitis, extending to the alveolar ridge, with dense infiltration of plasma cells, lymphocytes, macrophages, polymorphonuclear leukocytes and a greater number of osteoclasts in the connective tissue, but with less vascular density within ICT than in periodontitis. In addition, foreign bodies are found in PI lesions. The histopathological differences between the two diseases in terms of inflammatory infiltration, vascularity, bone loss, and foreign bodies could partially explain the more rapid progression of PI than periodontitis, suggesting that PI should be taken seriously by physicians. Early diagnosis and treatment are essential to control the progression of PI. In addition, targeted therapy against specific inflammatory cells may become a new direction for PI treatment; reducing titanium particles released into peri-implant tissue by friction or electrochemical corrosion may help to prevent PI.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

Effectiveness and risk factors of supramalleolar osteotomy in treatment of varus-type ankle arthritis / 中国修复重建外科杂志

OBJECTIVE@#To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure.@*METHODS@#The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m 2 (range, 20.43-30.15 kg/m 2). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed.@*RESULTS@#The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05).@*CONCLUSION@#SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.

Gene polymorphisms of cytochrome B-245 alpha chain (CYBA) and cholesteryl ester transfer protein (CETP) and susceptibility to generalized aggressive periodontitis / 北京大学学报(医学版)

OBJECTIVE@#To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP).@*METHODS@#The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model.@*RESULTS@#The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P < 0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P < 0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P < 0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P < 0.01), compared with those carrying CC and AA/AG genotypes.@*CONCLUSION@#CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.

Analysis of vitamin D status among children under 7 years of age in some regions of China / 中华儿科杂志

Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.

Research on the application of comprehensive simulated delivery room skill training combined with improved objective teaching in obstetric nursing teaching / 中华医学教育探索杂志

Objective:To explore the application of comprehensive simulated delivery room skill training combined with improved objective teaching in obstetric nursing teaching.Methods:A total of 84 nurses who practiced in the Department of Obstetrics of Nanjing Hospital of Traditional Chinese Medicine from August 2019 to August 2020 were selected as the research objects, and were divided into control group and research group according to the sequence of admission of practice nurses, with 42 nurses in each group. The control group adopted traditional teaching methods, and the research group adopted comprehensive simulated delivery room skill training combined with improved target teaching mode. The teaching effect of the two groups of practice nurses was evaluated by theoretical assessment, skill operation assessment and teaching satisfaction rate. SPSS 22.0 was used for t test and chi-square test. Results:The total score of theory assessment, single choice, multiple choice, blank filling, noun explanation, short answer and case analysis of practical nursing students in the study group were better than those in the control group, with statistically significant differences ( P<0.05). The results of practical skills operation and comprehensive quality ability evaluation of practice nurses in the study group were better than those in the control group, and the difference was statistically significant ( P<0.05). The teaching satisfaction rate of practice nurses in the control group was 80.95%(34/42), and that in the research group was 97.62%(41/42), with statistically significant differences ( χ2=6.10, P=0.014). Conclusion:The skill training of comprehensive simulated delivery room combined with improved objective teaching can improve the theoretical knowledge, practical skills and comprehensive quality of obstetric practice nurses, and improve the teaching satisfaction rate and obstetric nursing teaching quality of practical nurses.

The clinical value of enhanced whole-body CT in the early treatment of severe trauma / 中华急诊医学杂志

Objective:To investigate the significant effects of enhanced whole-body computed tomography (EWBCT) and non-enhanced whole-body computed tomography (N-EWBCT) on the missed diagnosis rate, renal function and prognosis of patients with severe trauma.Methods:Clinical data of trauma patients admitted from January 1, 2017 to December 31, 2020 were collected from the trauma database of the Trauma Center of the Second Affiliated Hospital of Soochow University. All patients included in this study were divided into the EWBCT group and N-EWBCT group according to whether they underwent enhanced whole-body computed tomography examination. The differences in baseline data, missed diagnosis rate, renal function and prognosis of the two groups of patients were compared.Results:A total of 459 patients were included in this study, including 184 patients in the EWBCT group and 275 patients in the N-EWBCT group. The missed diagnosis rate of the N-EWBCT group was significantly higher than that of the EWBCT group (18% vs. 5%, P < 0.01). The risk ratio of acute kidney injury (AKI) in the EWBCT group and N-EWBCT group was 9% and 7%, respectively, and there was no statistical difference between the two groups ( P >0.05). The mortality rate of patients in the N-EWBCT group was higher than that in the EWBCT group (23% vs. 12%, P=0.002). Conclusions:Compared with N-EWBCT, EWBCT does not significantly increase the risk of renal damage in patients with severe trauma. For patients with severe trauma, early EWBCT can reduce the missed diagnosis rate and improve the clinical prognosis.

Sanwubai San Inhibits TGF-β1 Induced Epithelial Mesenchymal Transition of Human Gastric Cancer SGC-7901 Cells Through TGF-β/ Smad Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of serum containing Sanwubai San on TGF-β1 induced epithelial mesenchymal transition （EMT） of human gastric cancer SGC-7901 cells and its mechanism in vitro based on transforming growth factor-β/Smad（TGF-β/Smad）signaling pathway. MethodTwenty-eight male SD rats （SPF grade， three months） were randomly divided into blank group and Sanwubai low （0.031 25 g·kg-1·d-1， ig）， medium （0.062 5 g·kg-1·d-1， ig） and high （0.125 g·kg-1·d-1， ig） dose groups， seven in each group. The blank group was given the same volume of ultrapure water （ig）. The gavage was performed once a day for seven consecutive days. The serum containing the drug was taken from the abdominal aorta 45 min after the last administration. Cell counting kit-8 （CCK-8） method was used to detect the effect of serum in Sanwubai San high dose group on the activity of SGC-7901 cells. Changes of cell morphology after treatment with TGF-β1 and serum containing Sanwubai San were observed by microscopy， and the migration rate and invasion rate of the SGC-7901 cells were detected by cell scratch assay and transwell assay， respectively. Western blot was used to detect the expression of E-cadherin， snail， TGF-β1， Smad3， p-Smad3 and Smad7 proteins. ResultCompared with the blank group， 10%， 15% and 20% high-dose Sanwubai San inhibited the activity of SGC-7901 cells in a concentration and time dependent manner. Compared with the conditions in the blank group， the cells in the model group lost spindle shape， and most cells became round and long. Compared with the model group， the Sanwubai San groups had decreased pseudopodia and small cells with the morphology returning to normal. Compared with the conditions in the blank group， enhanced ability of cell migration and invasion （P<0.01）， lowered expression of E-cadherin and Smad7 （P<0.01）， and increased expression of Snail， p-Smad3 and TGF-β1 （P<0.01） were found in the model group， with the total protein level of Smad3 remaining unchanged. Compared with the conditions in the model group， the cell migration ability was inhibited in the Sanwubai San high and medium dose groups （P<0.01） after 24 h， and the ability was inhibited in all three Sanwubai San groups after 48 h （P<0.01）， while the invasion ability was enhanced. In addition， the Sanwubai San high and medium dose groups had elevated expression of E-cadherin （P<0.01） and Smad7 （P<0.01）， and decreased expression of Snail （P<0.01）， and the expression of TGF-β1 and p-Smad3 was down-regulated in the three Sanwubai San groups （P<0.01）. ConclusionSanwubai San could inhibit TGF-β1 induced EMT in SGC-7901 cells， and its mechanism might be related to the regulation of TGF-β/Smad signaling pathway.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis / 国际口腔科学杂志·英文版

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

Exercises down regulate Toll-like receptor 4 signaling pathway in obese and overweight pregnant women / 中华围产医学杂志

Objective:To explore the effect of exercise intervention on regulation of Toll-like receptor 4 (TLR4) signaling pathway in overweight and obese pregnant women.Methods:The cohort was based on a randomized controlled trial (RCT) carried out by the same research group in Peking University First Hospital from December 2014 to July 2016. Overweight and obese patients who delivered by elective cesarean section without pregnancy complications were recruited, among which 12 cases in the exercise group and 11 cases in the control group were selected. Real-time polymerase chain reaction, Western Blot, and Luminex experiments were used to compare the expression of TLR4-myeloid differentiation factor 8(MyD88)-nuclear factor-κB(NF-κB) pathway in peripheral blood mononuclear cell (PBMC), rectus abdominis muscle, omental adipose, and subcutaneous adipose, as well as the levels of inflammatory factors (TNF-α, IL-1β, IL-10) in plasma between the two groups. Two independent samples t-test, generalized estimating equation, Chi-square test, and Pearson correlation analysis were adopted for statistical analysis. Results:(1) The expression of inflammatory factors TNF-α and IL-1β in the exercise group showed a downward trend compared with the control in the second and third trimester, but none of the differences were statistically significant (all P>0.05). (2) The mRNA expression of TLR4, MyD88, and NF-κB and the protein expression of TLR4 and NF-κB in PBMC of the exercise group were significantly lower than those in the control group during pregnancy (TLR4 mRNA: 0.06±0.03 vs 0.10±0.04 in the second trimester, 0.05±0.02 vs 0.11±0.05 in the third trimester, χ2=8.07; MyD88 mRNA: 0.09±0.03 vs 0.11±0.03 in the second trimester, 0.10±0.04 vs 0.17±0.06 in the third trimester, χ2=5.81; NF-κB mRNA: 0.10±0.03 vs 0.17±0.08 in the second trimester, 0.08±0.03 vs 0.20±0.08 in the third trimester, χ2=14.71; TLR4 protein: 1.7±0.5 vs 1.9±0.8 in the second trimester, 1.7±0.4 vs 2.3±0.8 in the third trimester, χ2=5.83; NF-κB protein: 1.0±0.4 vs 1.5±0.4 in the second trimester, 1.2±0.3 vs 1.5±0.5 in the third trimester, χ2=4.73; all P<0.05). Moreover, the differences in the mRNA expression of TLR4, MyD88, and NF-κB and TLR4 protein expression in PBMC between the two groups gradually increased. (3) NF-κB in rectus abdominis and omental adipose tissue (0.04±0.02 vs 0.08±0.04, t=－3.72; 0.25±0.05 vs 0.63±0.21, t=－5.41; both P<0.05) and TLR4 and MyD88 in subcutaneous adipose tissue (0.12±0.03 vs 0.30±0.10, t=－5.30; 0.24±0.09 vs 0.44±0.08, t=－5.38; both P<0.05) were observed a decreased mRNA level in the exercise group compared with the control group. The protein level of MyD88 and NF-κB in omental adipose tissue and NF-κB in subcutaneous adipose tissue in the exercise group were significantly lower than those in the control group (1.1±0.5 vs 2.0±0.8, t=－3.15; 1.3±0.5 vs 2.0±0.9, t=－2.23; 1.2±0.5 vs 1.9±0.8, t=－2.80, all P<0.05). (4) The expressions of TLR4 and NF-κB mRNA ( r=0.453 and 0.485) in rectus abdominis muscle, NF-κB mRNA, TLR4 and MyD88 protein ( r=0.539, 0.437 and 0.527) in omental adipose in the two groups were positively correlated with the level of fasting blood glucose ( P<0.05). Conclusions:Regular exercise during pregnancy can down-regulate the expression and activation of the TLR4-MyD88-NFκB pathway in overweight and obese pregnant women. The expression of related factors along this pathway has a certain correlation with fasting blood glucose.

Development of bioprinting technology and its application in bone tissue engineering / 中华骨科杂志

In recent decades, bone tissue engineering has made great progress in the treatment of large bone defects, among which bioprinting is one of the most important technologies. 3D bioprinting achieves precise control of the spatial structure of bone tissue engineering scaffold manufacturing by adding different materials in layers, and cells are placed into the scaffolds based on hydrogel materials to solve the uniform distribution of cells in the scaffolds. However, most biomedical materials used for 3D bioprinting are static and cannot be changed with the dynamics of the body's internal environment. 4D bioprinting combines the concept of time with 3D bioprinting and uses stimulus-responsive materials to change their shape under various stimuli to create dynamic 3D biological structures. It offers unprecedented potential for bone tissue engineering. The shape memory properties of printed structures meet the needs of personalized bone defect repair, and functional maturation procedures promote osteogenic differentiation of stem cells. In this paper, we review the commonly used 3D bioprinting methods and the mechanism of functional and morphological transformation in 3D bioprinting developed into 4D bioprinting technology by summarizing the research on bioprinting and tissue engineering at home and abroad in recent years. What's more, we introduce the application of bioprinting in the treatment of bone defects in bone tissue engineering as well as the current challenges and future prospects.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice.Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS.CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

Effect of Tai Chi and Resistance Training on Cancer-Related Fatigue and Quality of Life in Middle-Aged and Elderly Cancer Patients / 中国结合医学杂志

OBJECTIVE@#To study the effect of Tai Chi (TC) and resistance training (RT) with different intensity on the cancer-related fatigue (CRF) and quality of life (QoL) of middle-aged and elderly cancer patients.@*METHODS@#Totally 120 cancer patients were enrolled and randomly assigned to 4 groups by a random number table, including TC group, high-intensity 60% one repetition maximum (1-RM) RT group (HIRT), low-intensity (30% 1-RM) RT group (LIRT) and control group, 30 patients in each group. Participants in the TC group received 24-form simplified Yang-style TC training at a frequency of 40 min per day, 3 days per week for 12 weeks. Patients in the two RT groups received 10 sessions, 6 designated movements per day, 3 days per week for 12 weeks. The 1-RM of 6 muscle groups, fat mass (FM), lean body mass (LBM), along with the scores of Brief Fatigue Inventory (BFI), QoL questionnaire for Chinese cancer patients receiving chemobiotherapy (QLQ-CCC), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Pittsburgh Sleep Quality Index (PSQI) were measured before and after training. The adverse effect was also observed.@*RESULTS@#After 12-week intervention, patients in both TC and RT groups showed significant improvements in CRF and QLQ-CCC compared to pre-treatment (P<0.05). Compared with the LIRT and TC groups, patients in the HIRT group improved more significantly in increasing muscle strength and LBM, and reducing in FM (P<0.05). Patients in the TC group significantly increased in lower limb muscle strength compared with the LIRT group (P<0.05). In addition, patients in the TC group showed more significant improvements in scores of GAD-7, PHQ-9 and PSQI than 2 RT groups (P<0.05).@*CONCLUSIONS@#TC and RT, both low- and high-intensity training, can significantly increase muscle strength, reduce CRF and improve QoL in the middle-aged and elderly cancer patients. TC has a better effect than RT in terms of sleep quality and mental health. The long-term application is needed to substantiate the effect of TC as an alternative exercise in cancer patients.

Correlation of An Ultrasonic Scoring System and Intraoperative Blood Loss in Placenta Accreta Spectrum Disorders: A Retrospective Cohort Study / 生物医学与环境科学（英文）

Objective@#This study aims to investigate the correlation of an ultrasonic scoring system with intraoperative blood loss (IBL) in placenta accreta spectrum (PAS) disorders.@*Methods@#A retrospective cohort study was conducted between January 2015 and November 2019. Clinical data for patients with PAS have been obtained from medical records. Generalized additive models were used to explore the nonlinear relationships between ultrasonic scores and IBL. Logistic regressions were used to determine the differences in the risk of IBL ≥ 1,500 mL among groups with different ultrasonic scores.@*Results@#A total of 332 patients participated in the analysis. Generalized additive models showed a significant positive correlation between score and blood loss. The amount of IBL was increased due to the rise in the ultrasonic score. All cases were divided into three groups according to the scores (low score group: ≤ 6 points, @*Conclusions@#The risk of blood loss equal to or greater than 1,500 mL increases further when ultrasonic score greater than or equal to 10 points, the preparation for transfusion and referral mechanism should be considered.

The effects of combining aerobic training with resistance training on the heart rate and exercise capacity of persons with obstructive sleep apnea / 中华物理医学与康复杂志

Objective:To explore the effect of individualized aerobic training combined with resistance training on heart rate recovery and exercise capacity among patients with obstructive sleep apnea syndrome (OSAS) and explore possible mechanisms.Methods:Forty middle-aged patients with moderate to severe OSAS were randomly assigned to an observation group (OG, n=20) or a control group (CG, n=20). Both groups were given routine health guidance and motor training, while the OG additionally underwent individualized aerobic exercise training at 60%~75% of their peak power and resistance training loaded at 60%~80% of their ten-times maximum repetition figure. The training was three times a week for 3 months. Both groups underwent cardiopulmonary exercise testing and polysomnography before and after the 12-week intervention. The changes in their sleep apnea hypopnea index (AHI), oxygen desaturation index (ODI) and lowest oxygen saturation (L-SAO 2) were collected. Exercise capacity indicators such as peak oxygen uptake (VO 2peak), peak power, anaerobic threshold and sitting heart rate recovery (HRR) 1, 2 and 3 minutes after the test were recorded (denoted as HRR-1, HRR-2 and HRR-3). Results:There were no significant differences between the two groups in any of the measurements before the intervention. Afterward the average AHI, ODI and L-SAO 2 values of the observation group had all improved significantly compared with those before the training and compared with the control group′s values after the training. After the training, the VO 2peak and peak power of the observation group had also improved significantly compared with before the training and compared with the control group. HRR-1, HRR-2 and HRR-3 were all significantly higher in the observation group than before the training and higher than the control group′s values after the training. Conclusion:Combining aerobic and resistance training can improve the exercise ability and heart rate of middle-aged patients with moderate to severe OSAS, and also reduce the severity of their OSAS to some extent.

Efficacy of hemoperfusion in the treatment of severe organophosphorus poisoning in patients and its effects on diaphragm function / 中国基层医药

Objective:To investigate the clinical efficacy of hemoperfusion in the treatment of severe organophosphorus poisoning and its effect on diaphragm function.Methods:Eighty-five patients with severe organophosphorus poisoning who received treatment in Affiliated Huxi Hospital of Jining Medical University (Shanxian Central Hospital), China between January 2018 and January 2020 were included in this study. They were randomly divided into treatment ( n = 43)and control ( n = 42) groups. The control group was given conventional treatment including gastric lavage, catharsis, and application of reactivators and anticholinergic drugs. The treatment group was subjected to three times of hemoperfusion, with an interval of 24 hours between two hemoperfusion interventions based on the conventional treatment used in the control group. Before and after three times of hemoperfusion, serum levels of cholinesterase (CHE), interleukin-6 (IL-6), arterial partial pressure of oxygen (PaO 2), and arterial partial pressure of carbon dioxide (PaCO 2) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and oxygenation index (OI) in each group were calculated. Right diaphragmatic activity, diaphragmatic thickness at the end of inspiration (DTei) and diaphragmatic thickness at the end of expiration were measured by bedside ultrasound. The diaphragmatic thickening rate (DTF) and diaphragmatic rapid shallow breathing index (D-RSBI) were calculated. Serum CHE and IL-6 levels, OI, diaphragmatic activity, DTF and D-RSBI were compared between the treatment and control groups. The incidence of intermediate syndrome, tracheal intubation rate, 28-day mortality rate, and hospital stay were compared between the two groups. Results:Before hemoperfusion, there were no significant differences in serum levels of CHE and IL-6, OI, right diaphragmatic activity, DTF, and D-RSBI between the treatment and control groups (all P > 0.05). After three times of hemoperfusion, serum IL-6 level and D-RSBI in the treatment group were (37.9 ± 6.2) ng/L and (0.77 ± 0.20) times /min/mm, which were significantly lower than those in the control group [(45.9 ± 5.3) ng/L, (0.90 ± 0.16) times/min/mm ( t = -6.295, -3.382, P < 0.001, P = 0.001)]. Serum CHE level, OI, DE and DTF in the treatment group were (2.29 ± 0.52) kU/L, (264.5 ± 24.3) mmHg, (16.5 ± 1.9) mm, (27.2 ± 4.7) %, respectively, which were significantly higher than those in the control group [(1.96 ± 0.39) kU/L, (252.6 ± 27.2) mmHg, (14.3 ± 1.6) mm, (23.5 ± 4.1) %, t = 3.258, 2.141, 5.598, 3.877, all P < 0.05]. The incidence of intermediate syndrome, tracheal intubation rate, hospital stay in the treatment group were [4.7% (2/43)], [2.3% (1/43)] and [(11.8 ± 1.8) days], respectively, which were significantly lower than those in the control group [23.8% (10/42), 19.0% (8/42) and (12.9 ± 1.8) days, χ2 = 6.432, P = 0.011; χ2 = 6.276, P = 0.012; t = -2.932, P = 0.004]. There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Conclusion:Hemoperfusion can improve diaphragmatic function, reduce inflammatory reaction and shorten hospital stay in patients with severe organophosphorus poisoning.