Objective:To investigate the value of early tight junction protein Claudin-5 levels in predicting the severity of acute pancreatitis (AP).Methods:A prospective observational study was conducted, including patients diagnosed with AP and admitted to the Northern Jiangsu People's Hospital from December 1, 2021 to November 30, 2022. Eligible healthy volunteers were randomly selected to serve as healthy controls during the same period. Patients were classified into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group based on the 2012 Atlanta classification criteria. Patients with SAP were then divided into three subgroups of 1, 3, and 7 days based on the duration of hospitalization. Baseline data, such as gender, age, underlying disease, and probable etiology, was collected from all enrolled individuals. The enzyme-linked immunosorbent assay (ELISA) was employed to detect serum Claudin-5 levels in each cohort of enrollees. Data on additional serologic indicators, including hematocrit (HCT), albumin (Alb), serum Ca 2+, C-reactive protein (CRP), and procalcitonin (PCT) levels, were obtained via the in-hospital test query system in each group of patients with AP. The modified Marshall score (mMarshall), modified CT severity index (mCTSI) score, bedside severity index of severity in acute pancreatitis (BISAP) score, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) were recorded for each group of patients with AP. Differences in the above indicators between groups were analyzed and compared. Spearman's correlation method was employed to examine the relationship between Claudin-5 levels and each influential factor. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each influencing factor on SAP. Ridge regression was used to screen for independent risk factors for SAP. Results:A total of 109 patients with AP were enrolled, comprising 66 in the MAP group, 15 in the MSAP group, and 28 in the SAP group. Additionally, 27 healthy volunteers were enrolled as the healthy control group. No statistically significant differences were observed in gender and age among the enrolled groups, and no statistically significant differences were identified among the three groups of patients with AP in terms of underlying disease and etiologic composition. As the disease progressed, serum Claudin-5 levels exhibited a notable increase across all AP patient groups, and they were all significantly higher than those in the healthy control group [ng/L: 888.58 (574.52, 1 141.59), 3 749.02 (2 784.93, 5 789.92), 4 667.81 (3 935.21, 7 315.66) vs. 291.13 (250.19, 314.75), all P < 0.05]. Subgroup analyses showed that as the disease duration prolonged, patients in the SAP group exhibited a notable decline in Claudin-5 levels at 3 days post-admission, compared with those at 1 day post-admission [ng/L: 2 052.59 (1 089.43, 4 006.47) vs. 4 667.81 (3 935.21, 7 315.66), P < 0.05]. Spearman correlation analysis showed that serum Claudin-5 levels in patients with AP were significantly positively correlated with CRP, PCT, HCT, and mMarshall, mCTSI, and BISAP scores ( r values were 0.570, 0.525, 0.323, 0.774, 0.670, 0.652, all P < 0.001), and significantly negatively correlated with Alb ( r = -0.394, P < 0.001). A significant trend was observed in patients with AP, with an increase of HCT levels and a decrease of Alb levels as the disease progressed (both P < 0.05). An improvement of aforementioned phenomena was observed in patients with SAP following treatment, indirectly indicating that serum Claudin-5 level was a positive indicator of vascular leakage. ROC curve analysis showed that serum Claudin-5 levels in patients with AP exhibited the highest accuracy for early prediction of SAP, with the area under the ROC curve (AUC) of 0.948. When serum Claudin-5 levels ≥2 997 ng/L, the sensitivity for early screening for SAP was 100% and the specificity was 88.89%. Multifactorial ridge regression analysis showed that serum Claudin-5 level, PCT and APACHEⅡscore could be used as independent risk factors for early prediction of SAP (all P < 0.05). Conclusion:Serum Claudin-5 levels facilitate early prediction of SAP and are strongly associated with inflammatory response and vascular leakage.

Objective To explore the value of synchrotron radiation micro-CT(SR-pCT)and automatic marker watershed image segmentation for quantifying three-dimensional local bone tissue and blood vessels in mouse models of breast cancer tibia metastasis.Methods Mouse models with breast cancer bone metastasis in tibia were established and underwent oral Vatalanib,injection of Bevacizumab,combination of Vatalanib or Bevacizumab,or injection of placebo,respectively.On the 8th day(time point T1)and the 22nd day(time point T2)after injection of tumor cells,the tibia bone was scanned using combined vascular contrast injection and SR-pCT,and high-resolution simultaneous imaging of local bone tissue and vascular network were achieved.Then bone tissue and vessels on images were segmented using automatic marker watershed image-segmentation method,global threshold method and region growing method,respectively,and the quality of segmentations were assessed with Dice similarity coefficient(DSC).The anatomical quantitative parameters of tibia with breast cancer metastasis were obtained,including the fraction of bone volume in total volume(BV/TV),fraction of vessel volume in total volume(VV/TV),the mean thickness of bone(B.Th)and the mean thickness of vessel(V.Th).The anatomical quantitative parameters were compared among different treatments at the same time point,also between different time points under the same treatment.Results DSC for segmentation of local tibia bone tissue and vascular structures based on automatic marker watershed image segmentation method were all greater than 0.95,higher than that of other methods(all P＜0.05).No significant difference of anatomical quantitative parameters was found under different treatments at T1(all P＞0.05),and V.Th under the combined treatment were lower than that under other treatments at T2(all P＜0.05).Compared with T1,BV/TV and B.Th at T2 increased while VV/TV at T2 decreased in tibia metastasis under combination treatment(all P＜0.05),BV/TV,B.Th and V.Th at T2 increased under Vatalanib or Bevacizumab treatment(all P＜0.05),and BV/TV and B.Th at T2 increased under placebo(both P＜0.05).Conclusion The combination of SR-pCT and automatic marker watershed method could be used to initially quantify three-dimensional structures of local bone tissue and blood vessels in mouse models of breast cancer tibia metastasis.

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
Child ; Humans ; China ; Dwarfism ; Genetic Testing ; Heterozygote ; Syndrome

Objective:To compare the therapeutic effects of nasal high-flow oxygen therapy (HFNC) and nasal canal oxygenation (NCO) during breaks off non-invasive ventilation (NIV) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore the feasibility of NIV combined with HFNC in the treatment of AECOPD.Methods:From August 2017 to July 2019, AECOPD patients with type Ⅱrespiratory failure (arterial blood gas pH <7.35, PaCO 2 > 50 mmHg) who were treated with NIV were randomly (random number) assigned to the HFNC group and NCO group at 1:1. The HFNC group received HFNC treatment during breaks from NIV and the NCO group received low-flow NCO during the NIV interval. The primary endpoint was the total respiratory support time. The secondary endpoints were endotracheal intubation, duration of NIV treatment and breaks from NIV, length of ICU stay, total length of hospital stay and so on. Results:Eighty-two patients were randomly assigned to the HFNC group and the NCO group. After secondary exclusion, 36 patients in the HFNC group and 37 patients in the NCO group were included in the analysis. The total respiratory support time in the HFNC group was significantly shorter than that in the NCO group [(74 ± 18) h vs. (93 ± 20) h, P = 0.042]. The total duration of NIV treatment in the HFNC group was significantly shorter than that in the NCO group [(36 ± 11) h vs. (51 ± 13) h, P=0.014]. There was no significant difference of the mean duration of single break from NIV between the two groups, but durations of break from NIV in the HFNC group were significantly longer than those in the NCO group since the third break from NIV ( P < 0.05). The intubation rates of the HFNC and NCO groups were 13.9% and 18.9%, respectively, with no significant difference ( P=0.562). The length of ICU stay in the HFNC group was (4.3 ± 1.7) days, which was shorter than that in the NCO group [(5.8 ± 2.1) days, P=0.045], but there was no significant difference in the total length of hospital stay between the two groups. Heart rate, respiratory rate, percutaneous carbon dioxide partial pressure and dyspnea score during the breaks from NIV in the NCO group were significantly higher than those in the HFNC group, and the comfort score was lower than that in the HFNC group ( P<0.05). Conclusion:For AECOPD patients receiving NIV, compared with NCO, HFNC during breaks from NIV can shorten respiratory support time and length of ICU stay, and improve carbon dioxide retention and dyspnea. HFNC is an ideal complement to NIV therapy in AECOPD patients.

Objective To investigate the changes of hemoglobin levels in patients with ovarian cancer after chemotherapy and the influence of anemia on the prognosis of patients.Methods A total of 73 patients with ovarian cancer were selected.SPSS 25.0 statistical software was used to analyze the changes of hemoglobin levels after chemotherapy.According to the hemoglobin content before chemotherapy,the patients were divided into anemia group (Hb ＞ 110 g/L) and non-anemia group (Hb ＜ 110 g/L).Log Rand was used to compare the difference of survival time between the two groups.COX model was used to analyze the related factors affecting the prognosis of ovarian malignant tumors.Results The hemoglobin content before and after six chemotherapy cycles were (108.24 ± 18.09) g/L and (100.17 ±21.06) g/L respectively,with significant difference (P =0.021).The incidence of anemia and the degree of anemia gradually increased.The rate of anemia after six cycles of chemotherapy was higher than before chemotherapy,with significant difference (P =0.027).Survival analysis showed that progression free survival (PFS) was significantly lower in the anemic group than in the non-anemic group (P =0.01).COX regression analysis showed that anemia,postoperative residual lesion size,and surgical clinical staging were independent factors affecting the prognosis of patients with ovarian malignant tumors.Conclusions Chemotherapy reduces the hemoglobin content in patients with ovarian malignant tumors and aggravates anemia.Anemia affects the survival rate of patients with ovarian malignant tumors and is an independent factor affecting the prognosis of patients.

Objective To compare the efficacy of high flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of chronic obstructive pulmonary disease (COPD) with acute-moderate type Ⅱ respiratory failure,and to explore the feasibility of HFNC in the treatment of COPD with respiratory failure.Methods Patients diagnosed with COPD with acute moderate type Ⅱ respiratory failure (Arterial blood gas pH 7.25-7.35,PaCO2＞ 50 mmHg) admitted to the ICUs from April 2017 to December 2017 were retrospectively analyzed.All patients who were treated with HFNC within the first 4 hours after the admission to the ICUs,and continued for more than 2 hours and for at least 4 hours within the first 24 hours were included in the HFNC group.Those treated with NIV in the same conditions were included in the NIV group.The end point was the failure rates of treatment (changing to respiratory support method in another group or invasive ventilation) and 28-day mortality.Results Eighty-two patients (39 in the HFNC group and 43 in the NIV group) were enrolled.The HFNC group had a treatment failure rate of 28.2％,which was lower than that of the NIV group (39.5％).However,Kaplan-Meier curve analysis showed no significant difference between the two groups (Log Rank test 1.228,P=0.268).The 28-day mortality rate in HFNC group was 15.4％,which was no different from 14％ in NIV group (Log Rank test 0.049,P=0.824).The number of airway care interventions within the first 24 hours was significantly lower in the HFNC group than in the NIV group [5 (3～8) vs.11 (7～15)],whereas the duration of respiratory support within the first 24 hours was significantly longer in the HFNC group than in the NIV group [16 (9～22) hours vs.8 (4～11) hours] (all P＜0.05).The incidence of nasal facial lesions in the NIV group was 20.9％,significantly higher than that of HFNC group (5.1％,P ＜0.05).Conclusion For COPD with acute moderate type Ⅱ respiratory failure,HFNC has similar therapeutic effects as NIV.HFNC has better therapeutic tolerance and is a new potential respiratory support method for clinical treatment of COPD with respiratory failure.

Objective To approach the predictive value of continuous monitoring end-tidal carbon dioxide partial pressure (PETCO2) on the outcome of in-hospital cardiopulmonary resuscitation (CPR), and explored the indicators of termination of resuscitation. Methods A secondary analysis of a multicenter observational study data was conducted. The screening aim was adult non-traumatic in-hospital CPR patients whose PETCO2were recorded within 30 minutes of CPR. Clinical information was reviewed. The mean PETCO2in restoration of spontaneous circulation (ROSC) and non-ROSC patients was recorded. The outcome of CPR was continuously assessed by PETCO2≤ 10 mmHg (1 mmHg = 0.133 kPa) for 1, 3, 5, 8, 10 minutes. Receiver operating characteristic (ROC) curve was plotted, and the predictive value of PETCO2≤ 10 mmHg for different duration on the outcome of CPR was evaluated. Results A total of 467 recovery patients, including 419 patients with complete recovery were screened. Patients who were out-of-hospital resuscitation, non-adults, traumatic injury, had no PETCO2value, PETCO2value failed to explained the clinical conditions, or patients had not monitored PETCO2within 30 minutes of resuscitation were excluded, and finally 120 adult patients with non-traumatic in-hospital resuscitation were enrolled in the analysis. The mean PETCO2in 50 patients with ROSC was significantly higher than that of 70 non-ROSC patients [mmHg: 17 (11, 27) vs. 9 (6, 16), P < 0.01]. ROC curve analysis showed that the area under ROC curve (AUC) of PETCO2during the resuscitation for predicting recovery outcome was 0.712 [95% confidence interval (95%CI) = 0.689-0.735]; when the cut-off was 10.5 mmHg, the sensitivity was 57.8%, and the specificity was 78.0%, the positive predictive value (PPV) was 84.6%, and negative predictive value (NPV) was 46.9%. The duration of PETCO2≤ 10 mmHg was used for further analysis, which showed that with PETCO2≤10 mmHg in duration, the prediction of the sensitivity of the patients failed to recover decreased from 58.2% to 28.2%, but specificity increased from 39.4% to 100%; PPV increased from 40% to 100%, and NPV decreased from 57.5% to 34.2%. Conclusion For adult non-traumatic in-hospital CPR patients, continuous 10 minutes PETCO2≤10 mmHg may be an indicate of termination of CPR.

BACKGROUND:Previous studies have found that electroacupuncture can delay articular cartilage degeneration mediated by JAK-STAT signaling pathway through upregulating the expression level of transforming growth factor β1 as well as mRNA expression levels of STAT3, Smad3 and LepR. In the meanwhile, electroacupuncture can inhibit the mRNA expression of p38 and Fas mRNA mediated by MAPK signaling pathways, further inhibiting the apoptosis of chondrocytes. OBJECTIVE: To explore the effect of electroacupuncture on the degeneration of articular cartilage in rats with knee osteoarthritis based on Ras-Raf-MEK1/2-ERK1/2 signaling pathway. METHODS:120 male healthy Sprague-Dawley rats aged 2 months olds were selected and randomly divided into normal, model, 15-minite electroacupuncture and 30-minute electroacupuncture groups (n=30 per group). The rats in the latter three groups received the intra-articular injection of 4% papain bilaterally, and the remaining rats received no intervention. At 2 weeks after modeling, the latter two groups were respectively given 15- and 30-minute electroacupuncture, five times weekly for consecutive 12 weeks. The morphology of the cartilage was observed by hematoxylin-eosin staining, the expression level of interleukin-1β in the synovium was detected by ELISA assay, and the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were detected by western blot analysis. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that: in the model group, the cartilage surface was rough, the cartilage layer became thinner, and the cartilage structure was damaged with incomplete tidal line; in the 15- and 30-minute electroacupuncture groups, the cartilage structure was complete with clear layers and complete tidal line. ELISA showed that the expression level of interleukin-1β in the model group was significantly higher than that in the normal group (P< 0.01), and the level in the 15- and 30-minute electroacupuncture groups was significantly lower than that in the model group (P < 0.05). Western blot assay found that compared with the normal group, the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were increased in the model group. However, all above protein levels except ERK1/2 in the 15- and 30-minute electroacupuncture groups were significantly lower than those in the model group (P < 0.01,P < 0.05). To conclude, electroacupuncture inhibits the degeneration of articular cartilage in osteoarthritisvia Ras-Raf-MEK1/2-ERK1/2 signaling pathway and downregulating the expression level of interleukin-1β.

Objective To observe the effect of different airway pressure on ventilation, organ perfusion and return of spontaneous circulation (ROSC) of cardiac arrest (CA) pigs during cardiopulmonary resuscitation (CPR), and to explore the possible beneficial mechanism of positive airway pressure during CPR. Methods Twenty healthy landrace pigs of clean grade were divided into low airway pressure group (LP group, n = 10) and high airway pressure group (HP group, n = 10) with random number table. The model of ventricular fibrillation (VF) was reproduced by electrical stimulation, and mechanical chest compressions and mechanical ventilation (volume-controlled mode, tidal volume 7 mL/kg, frequency 10 times/min) were performed after 8 minutes of untreated VF. Positive end expiratory pressure (PEEP) in LP group and HP group was set to 0 cmH2O and 6 cmH2O (1 cmH2O = 0.098 kPa) respectively. Up to three times of 100 J biphasic defibrillation was delivered after 10 minutes of CPR. The ROSC of animals were observed, and the respiratory parameters, arterial and venous blood gas and hemodynamic parameters were recorded at baseline, 5 minutes and 10 minutes of CPR. Results The number of animals with ROSC in the HP group was significantly more than that in the LP group (8 vs. 3, P < 0.05). Intrathoracic pressure during chest compression relaxation was negative in the HP group, and its absolute value was significantly lower than that in LP group at the same time [intrathoracic negative pressure peak (cmH2O): -4.7±2.2 vs. -10.8±3.5 at 5 minutes, -3.9±2.8 vs. -6.5±3.4 at 10 minutes], however, there was significantly difference only at 5 minutes of CPR (P < 0.01). Intrathoracic pressure variation during CPR period in the HP group were significantly higher than those in the LP group (cmH2O: 22.5±7.9 vs. 14.2±4.4 at 5 minutes, 23.1±6.4 vs. 12.9±5.1 at 10 minutes, both P < 0.01). Compared to the LP group, arterial partial pressure of oxygen [PaO2 (mmHg, 1 mmHg = 0.133 kPa): 81.5±10.7 vs. 68.0±12.1], venous oxygen saturation (SvO2: 0.493±0.109 vs. 0.394±0.061) at 5 minutes of CPR, and PaO2 (mmHg: 77.5±13.4 vs. 63.3±10.5), arterial pH (7.28±0.09 vs 7.23±0.11), SvO2 (0.458±0.096 vs. 0.352±0.078), aortic blood pressure [AoP (mmHg): 39.7±9.5 vs. 34.0±6.9], coronary perfusion pressure [CPP (mmHg): 25.2±9.6 vs. 19.0±7.6], and carotid artery flow (mL/min:44±16 vs. 37±14) at 10 minutes of CPR in the HP group were significantly higher (all P < 0.05). Arterial partial pressure of carbon dioxide (PaCO2) in the HP group was significantly lower than that in the LP group at 10 minutes of CPR (mmHg: 60.1±9.7 vs. 67.8±8.6, P < 0.05). Conclusions Compared to low airway pressure, a certain degree of positive airway pressure can still maintain the negative intrathoracic pressure during relaxation of chest compressions of CPR, while increase the degree of intrathoracic pressure variation. Positive airway pressure can improve oxygenation and hemodynamics during CPR, and is helpful to ROSC.