Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

OBJECTIVE To explore the effects of Yupingfeng granules on the improvement of epithelial barrier function and the inhibition of tumor metastasis by regulating epithelial-mesenchymal transition （EMT）. METHODS Thirty C57BL/6 mice were randomly divided into the normal group （distilled water），model group （distilled water） and Yupingfeng granule group （40 g/kg）， with 10 mice in each group. The model group and Yupingfeng granule group were inoculated with Lewis lung cancer cells subcutaneously in the right armpit to induce the spontaneous lung metastasis model. After modeling，each group was given water/ relevant medicine intragastrically，once a day，for 15 consecutive days. The effects of Yupingfeng granules on tumor metastasis were investigated by observing or determining the pathomorphology of lung tissue，metastatic lesion count on the surface of the lung， tumor metastatic lesion and the expression of carcinoembryonic antigens. qRT-PCR and Western blot assay were used to detect the mRNA and protein expressions of β-catenin，E-cadherin and vimentin in the lung tissue of mice. RESULTS Compared with the model group，the total number of pulmonary metastases on the surface was decreased significantly in Yupingfeng granule group （P＜ 0.05），the general morphology of lung tissue was recovered，and the expression of carcinoembryonic antigen in lung tissue was significantly decreased （P＜0.05）. mRNA and protein expressions of E-cadherin in lung tissue were significantly increased （P＜ 0.05），while mRNA and protein expressions of vimentin and β-catenin were significantly decreased （P＜0.05）. CONCLUSIONS Yupingfeng granules can inhibit EMT by regulating the expression of β-catenin，thus improving epithelial barrier function，and inhibiting the ability of tumor cells to invade and metastasize.

Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.

Objective: This study aimed to estimate the clinical effects of different types of bone-anchored maxillary protraction devices by using a network meta-analysis. Methods: We searched seven databases for randomized and controlled clinical trials that compared bone-anchored maxillary protraction with tooth-anchored maxillary protraction interventions or untreated groups up to May 2021. After literature selection, data extraction, and quality assessment, we calculated the mean differences, 95% confidence intervals, and surface under the cumulative ranking scores of eleven indicators. Statistical analysis was performed using R statistical software with the GeMTC package based on the Bayesian framework. Results: Six interventions and 667 patients were involved in 18 studies. In comparison with the tooth-anchored groups, the bone-anchored groups showed significantly more increases in Sella-Nasion-Subspinale (°), Subspinale-Nasion-Supramentale(°) and significantly fewer increases in mandibular plane angle and the labial proclination angle of upper incisors. In comparison with the control group, Sella-NasionSupramentale(°) decreased without any statistical significance in all treated groups. IMPA (angle of lower incisors and mandibular plane) decreased in groups with facemasks and increased in other groups. Conclusions Bone-anchored maxillary protraction can promote greater maxillary forward movement and correct the Class III intermaxillary relationship better, in addition to showing less clockwise rotation of mandible and labial proclination of upper incisors. However, strengthening anchorage could not inhibit mandibular growth better and the lingual inclination of lower incisors caused by the treatment is related to the use of a facemask.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective: To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy. Methods: The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis. Results: There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m². (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m^2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m^2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m^2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ²=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D₁ lymph lode dissection, D₂ lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ²=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ²=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05). Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.

The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.

Objective To explore the clinical efficacy of Da Vinci robot-assisted iliofemoral vein bypass grafting.Methods The retrospective descriptive study was conducted.The clinical data of one 66-year-old male patient who underwent Da Vinci robot-assisted iliofemoral vein bypass grafting in the First Affiliated Hospital of Army Military Medical University in March 2019 were collected.The patient was failed to recanalize iliofemoral vein stent thrombosis by endovascular measures and underwent Da Vinci robot-assisted iliofemoral vein bypass grafting after balloon occlusion preset in the common iliac vein.Observation indicators:(1) intra-and postoperative situations;(2) follow-up and survival situations.Follow-up using outpatient examination was performed to detect the patient's postoperative survival and swelling reduction of affected extremity up to April 2019.Results (1) Intra-and post-operative situations:the patient underwent Da Vinci robot-assisted iliofemoral vein bypass grafting successfully.The operation time of balloon occlusion preset by digital subtraction angiography was 35 minutes.The operation time of Da Vinci robot-assisted iliofemoral vein bypass grafting was 502 minutes (50 minutes of exposure time of femoral vein,80 minutes of exposure time of iliac vein,40 minutes of great saphenous vein harvesting time,70 minutes of end to side anastomosis between autogenous great saphenous vein and femoral vein,10 minutes of subcutaneous tunnel construction,90 minutes of end to side anastomosis between autogenous great saphenous vein and iliac vein,60 minutes of suturing except vessel closure,102 minutes of preparation time,check and washing time).The volume of intraoperative blood loss was 500 mL and no intraoperative complications occurred.The autogenous great saphenous vein graft was well filled and no bleeding was found at both proximal and distal anastomoses after iliofemoral vein bypass grafting.There were 4 abdominal Trocar holes including 2 of 1.2 cm and 2 of 0.8 cm.The incisional length of right groin and left great saphenous vein harvesting region was 5.0 cm and 15.0 cm,respectively.At the discharge time,the patient had swelling subsided partially at right lower extremity and skin tesion reduced significantly compared with the admission.The perimeters at 15 cm above right knee joint and left knee joint were 53.5 cm and 48.0 cm.The maximum perimeters of right calf and left calf were 41.0 cm and 38.0 cm.No postoperative complications occurred.Duration of hospital stay after surgery was 3 days.(2) Follow-up and survival situations:the patient was followed up for 1 month,with good survival.The patient had swelling subsided of affected extremity.The perimeters at 15 cm above right and left knee joint were 52.0 cm and 48.0 cm.The maximum perimeters of right calf and left calf were 40.0 cm and 38.0 cm.Conclusion The Da Vinci robot-assisted iliofemoral vein bypass grafting is safe and feasible,with good short-term outcomes.