OBJECTIVE To investigate the efficacy and safety of doxycycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children under 8 years of age. METHODS The medical records of children with MUMPP admitted to the Women and Children’s Hospital Affiliated to Ningbo University were collected from January 1st， 2023 to December 31st， 2023. They were divided into doxycycline group （44 cases）， doxycycline combined with methylprednisolone group （35 cases）， and azithromycin combined with methylprednisolone group （35 cases） according to the treatment methods. Doxycycline group was given Doxycycline hyclate enteric-coated capsules； doxycycline combined with methylprednisolone group was given Doxycycline hyclate enteric-coated capsules and Methylprednisolone sodium succinate for injection； azithromycin combined with methylprednisolone group was given Azithromycin for injection and Methylprednisolone sodium succinate for injection. Treatment courses of 3 groups lasted for 10 d. The fever reduction rate， the time of fever reduction and improvement rate of lung infection absorption were compared among the three groups. The occurrence of adverse drug reactions was recorded during their hospitalization and followed up within 5 months after discharge. RESULTS The fever reduction rats 48， 72 h after treatment and improvement rate of lung infection absorption in doxycycline group and doxycycline combined with methylprednisolone group were significantly higher than azithromycin combined with methylprednisolone group； the time of fever reduction was significantly shorter than azithromycin combined with methylprednisolone group （P＜0.05）； there was no statistical significance in the difference between the doxycycline group and the doxycycline combined with methylprednisolone group （P＞0.05）. There was no statistical significance in the incidence of rash， vomiting， abdominal pain， diarrhea， and elevated transaminases among the three groups during hospitalization and within 5 months after discharge （P＞0.05）. None of the children treated with doxycycline suffered from tooth discoloration or enamel hypoplasia. CONCLUSIONS Doxycycline has good efficacy and safety in therapy of MUMPP in children under 8 years of age； adjunctive coadministration of low-dose glucocorticoids does not necessarily result in significant additional efficacy.

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.

Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.

Objective To develop a nomogram for predicting the risks of early anastomotic recurrence(EAR)after primary bowel resection in patients with Crohn's disease(CD).Methods The patients with CD under-going preoperative magnetic resonance enterography(MRE)and primary bowel resection were enrolled in this retrospective study and divided into an EAR group(18 patients)and EAR-free group(12 patients).The EAR group included the patients having an endoscopic Rutgeerts score of≥I2 month or the need for anastomotic resection within 12 months after surgery.All the 38 indexes including preoperative demographic characteristics,laboratory examina-tions,multi-parameter MRE features of the resected intestine and its adjacent mesentery,histological findings,and postoperative pharmacotherapy were analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate binary logistic regression analysis were performed to identify independent risk factors to be incorpo-rated into the nomogram for predicting the risks of early anastomotic recurrence and the prediction performance was evaluated.Results Mesenteric creeping fat index on MRE and comb sign were independent risks of EAR,with a concordance index of 0.882(95%CI:0.764～1).The calibration plot revealed a strong relationship between actual observation and predicted probability of EAR.Conclusions The preoperative MRE-based nomogram may be a potential tool for predicting EAR following surgery in patients with CD,which is beneficial to individual management in those patients.It provides reference for the formulation of early postoperative individualized drug adjuvant therapy in patients at high risk of EAR.

BACKGROUND:Circular RNAs(circRNAs)play important roles in a variety of diseases or tumors,and recent findings have revealed that circRNAs are abnormally expressed in knee osteoarthritis and are involved in disease progression through microRNA/mRNA regulation. OBJECTIVE:To investigate the effect of circRNA WD repeat containing protein 1(circ-BRWD1)/miR-488-3p/DNA methyltransferase 3A(DNMT3A)on the proliferation and apoptosis of chondrocytes in knee osteoarthritis. METHODS:Real-time fluorescence quantitative PCR was performed to detect the expression of circ-BRWD1,miR-488-3p,DNMT3A in knee osteoarthritis chondrocytes.Cells were divided into si-NC group,si-circ-BRWD1 group,vector group,circ-BRWD1 group,si-circ-BRWD1+anti-miR-NC group,si-circ-BRWD1+anti-miR-488-3p group,miR-NC group,miR-488-3p group,anti-miR-NC group,anti-miR-488-3p group,miR-488-3p+vector group,miR 488-3p+DNMT3A group.Real-time fluorescence quantitative PCR was used to detect circ-BRWD1,miR-488-3p,DNMT3A expression,MTT and flow cytometry assay were used to detect cell proliferation and apoptosis.Western blot assay was used to detect DNMT3A and proliferation/apoptosis-related protein expression.Dual luciferase reporter assay was used to Dual luciferase reporter assay to detect the targeting relationship of circ-BRWD1 with miR-488-3p and miR-488-3p with DNMT3A. RESULTS AND CONCLUSION:circ-BRWD1 and DNMT3A were highly expressed and miR-488-3p was lowly expressed in knee osteoarthritis chondrocytes compared with normal chondrocytes.Knockdown of circ-BRWD1 or overexpression of miR-488-3p inhibited proliferation and induced apoptosis in knee osteoarthritis chondrocytes.circ-BRWD1 targeted negative regulation of miR-488-3p and inhibition of miR-488-3p reversed the effect of circ-BRWD1 knockdown on chondrocyte proliferation and apoptosis in knee osteoarthritis.miR-488-3p targeted negative regulation of DNMT3A and upregulation of DNMT3A reversed the effect of miR-488-3p overexpression on chondrocyte proliferation and apoptosis in knee osteoarthritis.circ-BRWD1 could regulate the expression of DNMT3A by regulating miR-488-3p.To conclude,knockdown of circ-BRWD1 inhibits chondrocyte proliferation and induces apoptosis in knee osteoarthritis,and the mechanism of action may be related to the regulation of miR-488-3p/DNMT3A axis.

Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.