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OBJECTIVE To prepare Xiongzhi shigao decoction soluble microneedles， characterize it and investigate its transdermal properties in vitro. METHODS Two-step centrifugal method was used to prepare Xiongzhi shigao decoction soluble microneedles. The formability and mechanical property of the microneedles were evaluated from aspects of stroma fluidity， microneedle formability， needle hardness， etc. The appearance， mechanical strength， dissolution performance， skin barrier recovery performance and drug loading of the prepared microneedles were characterized by using active components of the soluble microneedle （chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide， isoimperatorin） as indicators. The in vitro transdermal performance was investigated by Franz diffusion cell. RESULTS The soluble microneedle tips of Xiongzhi shigao decoction prepared in this study were conical， evenly distributed and of the same thickness， with good mechanical properties； the tip of the needle could be almost completely dissolved after being penetrated into the skin of rats for 2 hours， and the skin barrier recovery performance was good； the drug loading of chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide and isoimperatorin were （87.04±1.12）， （67.69±1.23）， （20.65±0.17）， （35.00±0.11）， （153.83±0.21） and （23.52±0.50） μg per patch respectively. The results of in vitro transdermal study showed that cumulative release rates of 6 active components in this microneedle after 72 hours were 36.94%， 56.72%， 19.36%， 57.98%， 11.06% and 35.19%， respectively. CONCLUSIONS Xiongzhi shigao decoction soluble microneedles are prepared successfully in this study and have good formability， mechanical properties and pliable backing， which can significantly promote the transdermal drug delivery.
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AIM:To investigate the effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-Exos)on pulmonary vascular endothelial-mesenchymal transition(EndMT)in hypoxic pulmonary hypertension(HPH).METHODS:(1)Primary hUCMSCs were isolated and cultured by tissue adhesion method,and hUCMSC-Exos were extracted by ultrafiltration and identified.(2)Twenty-four SPF male SD rats were ran-domly divided into normoxia(N)group,hypoxia(H)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group,with 6 rats in each group.The rats in H group and intervention groups were placed in a cabin that simulated the hypoxic environment at an altitude of 5 000 m,and normoxic hUCMSC-Exos,hypoxia-precon-ditioned hUCMSC-Exos or equivalent volume of PBS were injected through the tail vein on the 3rd,5th,7th,10th and 14th days in hypoxia environment.After 21 d of modeling,the right ventricular systolic pressure(RVSP)and right ven-tricular hypertrophy index(RVHI)of the rats were detected,and the pathological changes of lung tissues were observed by HE staining.(3)After starvation for 12 h,human pulmonary arteriole endothelial cells(HPAECs)were randomly di-vided into normoxic control(N-Con)group,hypoxic model(H-Con)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group.The migration ability and tube formation ability of HPAECs were detected by Transwell assay and tube formation experiment.The expression of CD31 and α-smooth muscle actin(α-SMA)in HPAECs was detected by immunofluorescence double-staining.The protein levels of CD31,VE-cadherin,α-SMA and vimentin in pulmonary vessels and HPAECs were assessed by Western blot.RESULTS:(1)The HPH rat model was suc-cessfully established after 21 d of hypoxia,and EndMT occurred in pulmonary vessels.Compared with N group,the levels of RVSP,RVHI,percentage of vascular wall area(WA%)and percentage of vascular wall thickness(WT%)in H group were significantly increased(P＜0.01),pulmonary vascular wall thickening and the protein levels of CD31 and VE-cad-herin were significantly decreased(P＜0.01),while the protein levels of α-SMA and vimentin were significantly increased in pulmonary vessels(P＜0.05 or P＜0.01).Compared with H group,the RVSP,RVHI,WA%and WT%(P＜0.01)were significantly decreased(P＜0.05 or P＜0.01),and pulmonary vascular remodeling was attenuated after normoxic or hypoxia-preconditioned hUCMSC-Exos intervention.After hypoxia-preconditioned hUCMSC-Exos intervention,HPH pul-monary vascular remodeling and EndMT formation were significantly inhibited.(2)After 48 h of hypoxic treatment,the migration,tubule formation and EndMT of HPAECs were induced.Compared with H-Con group,cell migration and tube formation were significantly decreased after hypoxia-preconditioned hUCMSC-Exos intervention(P＜0.01).The protein levels of CD31 and VE-cadherin were increased,while the protein levels of α-SMA and vimentin were decreased(P＜0.05 or P＜0.01).CONCLUSION:Hypoxia-preconditioned hUCMSC-Exos attenuate the formation of HPH pulmonary vascu-lar remodeling by inhibiting pulmonary vascular EndMT.
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Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.
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Humans , Female , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , RNA, Competitive Endogenous , Cell Line, Tumor , Ovarian Neoplasms/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease （HFMD） in Minhang District， Shanghai from 2009 to 2020， and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics， temporal and spatial distribution of HFMD， the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020， a total of 66，198 cases of HFMD were reported in Minhang District， Shanghai， including 377 severe cases （severe case rate 0.57%） and 3 deaths （severs case fatality rate 0.80%）. There were more cases of HFMD in boys than in girls （1.5∶1）. HFMD patients aged under 5 years predominated， accounting for 88.91% of all cases. Majority of the cases （91.42%） were in scattered children （55.80%） and children in kindergartens （35.62%）. The incidence showed a cyclical trend， with low incidence years and high incidence years appearing alternately. The peak period was from April to July， and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town， Huacao Town and Xinzhuang Town， respectively. The proportion of EV71 in common cases was generally decreasing， and reduced to zero in 2019. The proportion of CoxA6 had increased year by year， and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010， and the dominant pathogen was EV71 （90.03% on average） in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6， and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District， and provides a scientific basis for epidemic prevention and control.
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Objective:To investigate the rationality of nerve-plane sparing radical hysterectomy (NPSRH) for cervical cancer by observing the anatomical and histological characteristics of pelvic autonomic plane based on fresh cadaver.Methods:From October 2015 to September 2020, 14 fresh female cadavers were anatomically and histologically studied in the Laboratory of Anatomy and Embryology Department, Peking Union Medical College, Chinese Academy of Medical Sciences. The median age of the specimens was 79 years (range: 67 to 92 years). Twenty-eight hemi-pelvic specimens were obtained from 14 fresh female cadavers. NPSRH procedures were simulated in 8 hemi-pelvic cavities to prove its feasibility. Detailed dissection was conducted to recognize nerve plane and to observe the distribution of pelvic nerves in 10 hemipelvis. In the other 10 hemipelvis, whole parametrium tissue was taken from the crossing of ureter and the uterine artery to the ureterovesical entrance and be embedded, then continuous section was performed, and was stained by hematoxylin-eosin staining (HE) to observe the relationship of nerves and vessels. Immunohistochemical staining of S100, tyrosine dehydrogenase (TH), and vasoactive intestinal peptide (VIP) were performed to count and distinguish sympathetic and parasympathetic nerves, respectively.Results:(1) The pelvic autonomic nerve-plane was completely preserved in 7 of 8 hemipelvis by simulating NPSRH. (2) After detailed dissection in 10 hemipelvis, it was found that hypogastric nerve, pelvic splanchnic nerve, and their confluence of inferior hypogastric plexus were distributed in a planar statelocating in the ureteral mesentery and its caudal extension. This nerve plane showed a cross relationship with deep uterine vein and its branches. The bladder branches and vesical venous plexus were closely related to the inferior hypogastric plexus. The middle vesical vein and inferior vesical vein were intact in 7 of 10 hemipelvis, and either vesical vein was missing in 3 of them. It was observed that the vesical venous plexus communicated with the deep uterine vein trunk on the medial side of the nerve plane in 6 hemipelvis, while flowed into the deep uterine vein on the lateral side of the nerve plane in 2 hemipelvis, and in the other 2 hemipelvis it directly flowed into the internal iliac vein. (3) It was revealed that autonomic nerves were continuously distributed beneath the ureteral with sagittal plane by HE staining. The average nerve content below the ureteral width was 70.9% of the total in nerve plane by S100 staining. TH and VIP staining showed that the average number of sympathetic fibers was 13.5 and parasympathetic fibers was 8.2, reminding sympathetic predominated.Conclusion:Pelvic autonomic nerves are mainly distributed within the mesangial plane below the ureter, which provides an anatomic justification for NPSRH.
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Purpose@#This study aimed to investigate the factors associated with chemoresistance to neoadjuvant chemotherapy (NACT) followed by radical hysterectomy (RH) and construct a nomogram to predict the chemoresistance in patients with locally advanced cervical squamous carcinoma (LACSC). @*Materials and Methods@#This retrospective study included 516 patients with International Federation of Gynecology and Obstetrics (2003) stage IB2 and IIA2 cervical cancer treated with NACT and RH between 2007 and 2017. Clinicopathologic data were collected, and patients were assigned to training (n=381) and validation (n=135) sets. Univariate and multivariate analyses were performed to analyze factors associated with chemoresistance to NACT. A nomogram was built using the multivariate logistic regression analysis results. We evaluated the discriminative ability and accuracy of the model using a concordance index and a calibration curve. The predictive probability of chemoresistance to NACT was defined as > 34%. @*Results@#Multivariate analysis confirmed menopausal status, clinical tumor diameter, serum squamous cell carcinoma antigen level, and parametrial invasion on magnetic resonance imaging before treatment as independent prognostic factors associated with chemoresistance to NACT. The concordance indices of the nomogram for training and validation sets were 0.861 (95% confidence interval [CI], 0.822 to 0.900) and 0.807 (95% CI, 0.807 to 0.888), respectively. Calibration plots revealed a good fit between the modelpredicted probabilities and actual probabilities (Hosmer-Lemeshow test, p=0.597). Furthermore, grouping based on the nomogram was associated with progression-free survival. @*Conclusion@#We developed a nomogram for predicting chemoresistance in LACSC patients treated with RH. This nomogram can help physicians make clinical decisions regarding primary management and postoperative follow-up of the patients.
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Objective:To evaluate the etiological diagnosis value of soft bronchoscopy in children with laryngeal stridor.Methods:The clinical data of 402 children with laryngeal stridor wheezing were retrospectively analyzed, which examined by soft bronchoscopy in Anhui Provincial Children′s Hospital from January 2016 to January 2019.Results:A total of 402 cases of laryngeal stridor were diagnosed by soft bronchoscopy, 317(78.8%) cases were diagnosed as congenital airway dysplasia, including 200(49.7%)cases of congenital laryngeal chondromalacia, which including 132 cases of single laryngeal chondromalacia and 68 cases with other respiratory tract dysplasia, and 117(29.1%) cases of respiratory dysplasia other than laryngeal chondromalacia; 46(11.5%) cases of laryngitis; 28(7.0%) cases of airway acquired stenosis and 11 (2.7%)cases of foreign body.Among 402 cases of children with laryngeal stridor who were diagnosed according to clinical feature, combined with chest X-ray, chest CT, CT angiography and color Doppler echocardiography as well as other imaging data, 335(83.3%) cases were congenital laryngeal chondromalacia, 16(4.0%) cases were other respiratory tract dysplasia (including six cases of subglottic and tracheal stenosis, five cases of laryngeal space occupying lesions, four cases of tracheobronchial malformation, and one case of subglottic hemangioma), 35 (8.7%)cases of laryngitis, acquired airway stenosis in 15 cases including 13 cases of congenital heart disease, one case of pulmonary artery sling, one case of mediastinal cyst, and one case of foreign body.Congenital laryngeal chondromalacia, other causes of respiratory dysplasia and foreign body detected by flexible bronchoscopy were not consistent with clinical examination( P<0.05). Conclusion:Congenital laryngeal chondromalacia is the main cause of laryngeal stridor, but it is often associated with other airway dysplasia.Soft bronchoscopy can provides etiological diagnosis for children with laryngeal stridor wheezing, especially in the diagnosis of respiratory tract dysplasia and airway foreign body.
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Objective:Evaluation of two-dimensional speckle tracking technique in the diagnosis of apical hypertrophic cardiomyopathy (AHCM) using ROC curve.Methods:100 patients with AHCM admitted to Kunshan First People's Hospital from June 1, 2014 to June 30, 2018 were selected as the observation group, and 50 healthy volunteers who underwent physical examination at the same time were selected as the control group. All subjects underwent two-dimensional echocardiography. Circumferential strain (CS) and longitudinal strain (LS) of each segment of the left ventricular wall were obtained. End-rot, epi-rot, bulk-rot, mural-tor and G-tor were measured at mitral and apical levels. To screen effective indicators and evaluate the diagnostic effect of each indicator by receiver operating characteristic (ROC) curve.Results:There were significant differences in end-diastolic volume, end-systolic volume, diameter of left atrium in end-systole, the height of the early diastolic flow-velocity peak (E), the height of the late diastolic peak (A), E/A and apical thickness in end-diastole between the two groups ( P<0.05). There were significant differences in CS at mitral valve level, apical level, papillary muscle level, global CS, LS and global LS (GLS) between the observation group and the control group ( P<0.05), the diagnostic value of combined CS and LS at apical level was higher, and the area under curve (AUC) was 0.821(0.791, 0.904); There were significant differences in mitral valve level and apical level of endo-rot, epi-rot, bulk-rot, mural-tor and G-tor between the observation group and the control group ( P<0.05); G-tor has higher diagnostic value among them, and the AUC was 0.844 (0.771, 0.918). Conclusions:Two-dimensional speckle tracking technique plays an important role in the diagnosis of apical hypertrophic cardiomyopathy. It can observe the ability of myocardial movement and deformation, as well as the changes of left ventricular myocardial rotation and torsion. The combined detection of CS and LS at apical level and G-tor can better differentiate AHCM.
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Objective:To investigate the efficacy and safety of laparoscopic radical hysterectomy for early cervical adenocarcinoma.Methods:A retrospective observational study was performed by reviewing medical records of patients with staging Ⅰb1-Ⅱa2 International Federation of Gynecology and Obstetrics (FIGO, 2009) cervical adenocarcinoma who underwent laparoscopic or abdominal radical hysterectomy from 2007 to 2017 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. The difference among clinicopathologic characteristics, surgery-related parameters and complications, and prognosis were analyzed between the laparoscopic group and abdominal group.Results:Two hundreds and ninety-three patients were included with 88 cases in laparoscopic group and 205 cases in abdominal group. （1） There was no significant difference in clinicopathologic characteristics between the two groups （all P>0.05）, including age, body mass index, menopause status, history of abdominal surgery, clinical stage, tumor diameter, neoadjuvant chemotherapy, differentiation, lymph-vascular space invasion, positive of surgical margin, parametrial invasion, and lymph node metastasis. But the abdominal group showed a higher proportion of deep stromal invasion (38.5% vs 25.0%, P<0.05). No significant difference was observed between two groups with number of lymph nodes resected, urinary catheter retention, short-term surgical complications (including ureteral injury, ileus, infection, hydronephrosis and poor wound healing), and long-term complications (including voiding dysfunction, defecation dysfunction and lower limb edema； all P>0.05）. （2） The laparoscopic group was significantly associated with a longer operation time [(260±51) minutes vs (244±53) minutes, P<0.05], but less bleeding (100 ml vs 300 ml, P<0.01), shorter hospital stay [(13±5) days vs (16±8) days, P<0.01] and lower incidence of lymphedema (12.5% vs 27.8%, P<0.01). （3） The 5-year progression-free survival (PFS; 85.7% vs 86.4%, P=0.971) and 5-year overall survival (OS; 91.4% vs 93.0%, P=0.657) of laparoscopic group were comparable to that of abdominal group. （4） Multivariate analysis demonstrated that lymph node metastasis ( HR=2.44, 95% CI: 1.16-5.15, P=0.019) was independent poor prognostic factors related to PFS, while adenosquamous carcinoma ( HR=2.54, 95% CI: 1.02-6.35, P=0.046), lymph-vascular space invasion ( HR=3.86, 95% CI: 1.60-9.33, P=0.003) and lymph node metastasis ( HR=5.92, 95% CI: 2.45-14.34, P<0.01) were independent poor prognostic factors related to OS. The laparoscopy surgery was not an independent poor prognostic factor ( P=0.396). Conclusion:The laparoscopic radical hysterectomy for early cervical adenocarcinoma has comparable prognosis to abdominal radical hysterectomy with a higher surgery quality.
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Objective To explore the feasibility and safety of radiofrequency ablation for difficult access liver cancer under percutaneous local anesthesia combined with contrast-enhanced ultrasonography.Methods 45 patients(62 lesions) in the experimental group were treated by percutaneous,local anesthesia combined with contrast-enhanced ultrasound and in some cases with artificial ascites assisted by radiofrequency ablation vs control group of 40 patients (54 lesions) receiving radiofrequency ablation guided by CT or ultrasound through laparoscopy or open surgery.The complications,and postoperative residual and recurrence rates were compared between the two groups.Results Of the all patients,4 cases suffered from severe complications.The pain scores and the blood loss were less significant in the experimental group.There was no significant difference in tumor residual rate between the two groups when evaluated on one month after the procedures,and in the recurrence rate after three and six months.Conclusion Radiofrequency ablation for difficult liver cancer by percutaneous local anesthesia combined with contrastenhanced ultrasonography is less traumatic and less of complications compared to traditional method with a similar tumor residual rate and recurrence rate.