ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

Objective:To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients.Methods:A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients.Results:A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (μg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF ( r = -0.377, P = 0.014) and 4DEF ( r = -0.697, P = 0.000), while no correlation was found with RVEF ( r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score ( r = 0.306, P = 0.033), while LVEF ( r = 0.112, P = 0.481), RVEF ( r = -0.134, P = 0.595), and 4DEF ( r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. Conclusion:GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.

Objective To explore the clinical application of individualized coil embolization in the interventional treatment of renal artery aneurysm(RAA).Methods Data of 23 patients with RAA treated by individualized coil embolization were analyzed.There were 27 RAAs,in which narrow-necked RAAs were treated with coil embolization and wide-necked RAAs were treated with stent-assisted coil embolization.The efficacy of the two embolization methods were analyzed and the changes of renal function and symptoms were observed.Results A total of 27 RAAs in 23 patients were successfully embolized at one time,including 23 narrow-necked RAAs in 19 cases treated with coil embolization and 4 wide-necked RAAs in 4 patients treated with stent-assisted coil embolization.The embolization effect of 20 cases(86.96%)reached Raymond grade Ⅰ,and 3 cases(13.04%)reached gradeⅡ.Postoperative computed tomography angiography(CTA)showed that all parent arteries were patent,the RAA was not visualized,and there was no renal infarction.There was no statistical difference in creatinine values before operation,1 month,6 months and 1 year after operation(P>0.05).In the 12 patients with hypertension,there were statistically significant differences in blood pressure at 1 year after operation compared with preoperative,1 month,and 6 months after operation(P<0.05).The symptoms of low back pain and hematuria disappeared after operation.Conclusion Individualized coil embolization for RAA is safe,effective and worthy of clinical promotion.

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Objective:To explore the clinical application value of DNA image cytometry ploidy analysis (DNA-ICM) in the pathological diagnosis of malignant pleural effusion.Methods:A retrospective case series study was conducted. The clinical data of 101 patients with pleural effusion from October to December 2021 in Shanxi Bethune Hospital were retrospectively analyzed. Liquid-based cytology (LBC) and DNA-ICM were performed on pleural effusion specimens. The sensitivity and specificity of the two methods were compared with the clinical diagnosis, imaging, biopsy, and follow-up results of the patients.Results:Among the pleural effusions of 101 patients, 39 were malignant pleural effusions and 62 were benign pleural effusions. The sensitivity of LBC and DNA-ICM in diagnosing malignant tumor cells in pleural effusions was 74.7% and 94.9%, respectively, and the specificity was 98.4% and 83.9%, respectively; the combination of the two had an increased diagnostic positivity rate compared with that of LBC alone [36.6% (37/101) vs. 28.7% (29/101)]. Seven cases with positive DNA-ICM but negative LBC result were followed up, and 1 case was diagnosed as small cell lung cancer. Conclusions:DNA-ICM can effectively improve the positive cytology detection rate of pleural effusion, and the combined detection of DNA-ICM and LBC can reduce the underdiagnosis rate of cytology, which is of great clinical value in the pathological diagnosis of malignant pleural effusion.

Due to the complexity of traditional Chinese medicine （TCM） interventions and the diversity of herbal components， single-omics technologies such as genomics， transcriptomics， proteomics， and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes， gene expression， proteins， and metabolites， in line with the holistic view of TCM， which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM， it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation， evaluation of herbal quality， elucidation of pharmacological mechanisms， and drug toxicity assessment， providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies， and having obtained significant achievements. However， multi-omics technologies also face challenges such as high cost， difficulties in data analysis due to large data volumes， and insufficient translation of research results. In the future， it is expected that through strengthening interdisciplinary cooperation， conducting long-term and dynamic clinical research， standardizing and normalizing data analysis processes， adopting appropriate and reasonable multi-omics integration patterns， establishing multi-omics databases for TCM， revealing the individualized characteristics， therapeutic mechanisms， and disease regulatory networks of TCM， the modernization of TCM will be promoted.

Objective To investigate the clinical efficacy and postoperative aortic changes of 3D printing-assisted stent with in-vitro pre-fenestration technique in the treatment of complex type B aortic dissection.Methods A retrospective analysis was conducted on 28 patients with complex type B aortic dissection who underwent thoracic endovascular aortic repair(TEVAR)using stent with in-vitro pre-fenestration technique.The patients were divided into two groups based on the methods of stent with in-vitro pre-fenestration:the 3D printing-assisted stent pre-fenestration group(3D printing group)consisting of 13 patients and traditional stent pre-fenestration group(traditional group)consisting of 15 patients.Various parameters,including hospital duration,surgical duration,duration of stent pre-fenestration in vitro,dose of contrast agent,intraoperative blood loss,immediate postoperative internal leakage rate,30 d postoperative internal leakage rate,30 d postoperative mortality,and the change rate of true and false lumen diameter[the change rate of true and false lumen diameter=(postoperative true and false lumen diameter-preoperative true and false lumen diameter)/preoperative true and false lumen diameter× 100％],were compared between the two groups.Results Compared with the traditional group,the 3D printing group exhibited a considerable reduction in surgical duration[(148.46±27.20)min vs(175.46±22.04)min,P＜0.05].Additionally,the 30 d postoperative type Ⅰ internal leakage rate was lower in the 3D printing group(X2=4.044,P=0.044).Moreover,the change(dilation)rate of true lumen diameter in stent coverage section showed a notable increase in the 3D printing group(P＜0.05).Conclusion The use of 3D printing-assisted stent with in-vitro pre-fenestration has been proven to be safe and effective in the treatment of complex type B aortic dissection.It offers notable advantages,including the reduction of surgical duration,a lower risk of type Ⅰ internal leakage and significant redilation of the true aortic lumen after surgery.

Humans ; Hypertension, Pulmonary/surgery* ; Learning Curve ; Angioplasty, Balloon ; Pulmonary Embolism/therapy* ; Chronic Disease ; Pulmonary Artery/surgery*

Objective:A single-center analysis was performed to assess the significant clinical features and prognostic factors of TFE3-rearranged renal cell carcinoma (TFE3 rRCC).Methods:The clinical data of 85 confirmed cases of TFE3 rRCC patients at the Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2007 to February 2023 were analyzed retrospectively. Among these patients, there were 39 males and 46 females, with a median age of 32 (26, 45) years. All patients underwent preoperative CT scans, 21/85 cases (24.7%) of TFE3 rRCC exhibited the characteristic feature of "circular calcification" with plain CT imaging, and enhanced CT scan showed that the tumor enhancement during the arterial phase was lower than the adjacent renal cortex. Among the 85 patients in this cohort, the median tumor diameter was 4.8(3.2, 6.5). Thirty-two patients underwent partial nephrectomy (NSS), while 51 patients underwent radical nephrectomy (RN). Two patients with distant metastasis at the time of diagnosis received only sunitinib therapy. Forty-three patients received adjuvant treatment, including 14 patients who received targeted therapy. There were 29 patients in AJCC stage Ⅲ/Ⅳ, with 10 patients presenting with venous tumor thrombus and 14 patients with lymph node metastasis. Histopathology, TFE3 immunohistochemistry, and break-apart TFE3 FISH probe detection were performed on all 85 cases, while 52 patients underwent RT-PCR and/or DNA sequencing. By combining the clinical and pathological data, we summarized the diagnostic Methods for TFE3 rRCC, evaluated the impact of surgical approaches (RN and NSS) on the survival outcomes of cT 1a/b patients, and assessed the influence of genetic subtypes (ASPL, NONO, PRCC, SFPQ, and others) on the survival outcomes of all patients. Furthermore, we analyzed the risk factors for disease progression. Results:TFE3 rRCC exhibited variable histopathological features, and the presence of acinar-like structures with psammoma bodies may be a relatively typical characteristic. All 85 patients showed positive TFE3 immunohistochemical staining. In 6 cases of TFE3 rRCC, break-apart TFE3 FISH probe yielded negative results. However, final confirmation was achieved through genetic sequence, with 5 cases diagnosed as NONO-TFE3 subtype and 1 case as RBM10-TFE3 subtype. Among the 85 patients, 52 underwent RT-PCR and/or DNA sequencing, revealing a total of 8 TFE3 fusion subtypes, including 11 cases of ASPL-TFE3, 8 cases of PRCC-TFE3, 10 cases of NONO-TFE3, 15 cases of SFPQ-TFE3, 1 case of CLTC-TFE3, 2 cases of LUC7L3-TFE3, 4 cases of MED15-TFE3, and 1 case of RBM10-TFE3. The survival analysis results revealed that among the 12 patients with cT 1b stage tumors who underwent radical nephrectomy (RN), the progression-free survival (PFS) was 35 (14, 109) months, which was significantly better than the NSS group ( P=0.041). However, for the 14 patients with cT 1a stage tumors who underwent RN, there was no statistically significant difference in overall survival (OS) and PFS compared to the NSS group, with OS being 55(27, 134) months and PFS being 71(41, 134) months. Stratifying according to TFE3 fusion subtypes, it was found that patients with ASPL-TFE3 fusion had a significantly lower PFS compared to those with non-ASPL-TFE3 fusion subtypes ( P=0.029). Survival analysis revealed that tumor diameter, surgical approach, adjuvant therapy, AJCC staging, venous tumor thrombus, and lymph node metastasis were associated with OS and PFS( P<0.05). The results of the multivariate Cox regression analysis showed that AJCC stage Ⅲ/Ⅳ( HR=2.393, 95% CI 1.418-4.039, P=0.001) and venous tumor thrombus ( HR=3.543, 95% CI 1.159-10.827, P=0.026) were independent risk factors for progression-free survival (PFS). Conclusions:During the non-enhanced phase of CT scan, TFE3 rRCC tumors can exhibit a circular calcification. TFE3 immunohistochemistry is an important screening method for TFE3 rRCC.Break-apart TFE3 FISH probe detection is considered the diagnostic gold standard, and gene sequencing, if feasible, can provide the subtype diagnosis of TFE3 rRCC. For cT 1a stage TFE3 rRCC, partial nephrectomy (NSS) is a viable option, while caution should be taken in selecting NSS for cT1b stage patients. Patients with ASPL-TFE3 fusion subtype have a worse prognosis. AJCC stage Ⅲ/Ⅳ and venous tumor thrombus indicate poor prognosis in TFE3 rRCC.