Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

Objective:To investigate the correlation between the clinical features and endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) in patients with cirrhosis.Methods:A total of 148 patients with cirrhosis and portal hypertension who underwent EUS-PPG measurement at the Third Xiangya Hospital of Central South University from March 15, 2022 to June 20, 2023 were selected. The clinical data of patients collected before EUS-PPG measurement were analyzed. Variations in the EUS-PPG across different clinical data subgroups were analyzed. Multivariate linear regression analysis was used to explore the independent factors influencing EUS-PPG.Results:The EUS-PPG was significantly elevated in patients exhibiting red signs (16.62±5.33 mmHg VS 13.44±5.34 mmHg, t=3.616, P<0.001), gastroesophageal varices (15.78±5.30 mmHg VS 9.70±4.77 mmHg, t=4.247, P<0.001), hepatic encephalopathy (20.83±7.52 mmHg VS 14.92±5.35 mmHg, t=2.606, P=0.010), thrombocytopenia (15.66±5.39 mmHg VS 13.29±5.83 mmHg, t=2.136, P=0.034), hypoproteinemia (16.13±5.86 mmHg VS 14.12±5.03 mmHg, t=2.230, P=0.027), and an increased international normalized ratio (16.25±6.00 mmHg VS 14.40±5.11 mmHg, t=2.022, P=0.045). Conversely, the EUS-PPG was significantly reduced in patients with a history of splenectomy and devascularization (13.17±5.88 mmHg VS 15.73±5.34 mmHg, t=-2.379, P=0.019). The EUS-PPG in patients with varying degrees of ascites (no VS slight VS moderate or severe: 13.40±5.48 mmHg VS 15.90±5.49 mmHg VS 16.69±5.17 mmHg, F=5.188, P=0.007) and different Child-Pugh classifications (A VS B VS C: 14.07±5.05 mmHg VS 15.69±5.74 mmHg VS 17.64±5.99 mmHg, F=3.066, P=0.049) increased gradually. Multivariable linear regression analysis showed that red signs ( β=2.44, t=2.732, P=0.007), gastroesophageal varices ( β=4.45, t=2.990, P=0.003), ascites ( β=1.75, t=2.368, P=0.019), and hepatic encephalopathy ( β=5.82, t=2.644, P=0.009) were independent factors for the elevated EUS-PPG. Conclusion:There is a significant correlation between EUS-PPG and the clinical features related to the severity of cirrhotic portal hypertension, which indicates the feasibility of EUS-PPG in evaluating cirrhotic portal hypertension.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

[Abstract] Objective: To investigate the pathogenesis of prostate cancer by analyzing the associated hub gene modules of prostate cancer and identifying key transcription factors and genes that affect these modules. Methods: WGCNA (weighted gene co-expressed network analysis) was used to identify hub gene modules associated with important clinicopathological features of prostate cancer, such as pathological staging, Gleason grading etc. The OPOSSUM online tool was used to analyze the transcription factors enriching and regulating those genes. Pathway enrichment analysis and protein-protein interaction network analysis were used to identify key genes in prostate cancer. Finally, the effects of these genes on clinical features and disease-free survival (DFS) of prostate cancer patients were analyzed. Results: Three hub modules were identified, and they were highly associated with pathologic T stage, pathologic N stage and Gleason grading of prostate cancer, respectively. Further screening revealed 13 key dysregulated transcription factors that participated in the regulation of these three hub modules. The differentially expressed genes regulated by the 13 key transcription factors were significantly enriched in Calcium signaling pathway, cGMP-PKG signaling pathway and cAMP signaling pathway. 14 key genes (PRKG1, PRKG2, CYSLTR2, GRPR, CHRM3, ADCY5, ADRA1D, EDNRA, EDNRB, CYSLTR2, AGTR1, GRPR, GRIA1 and OXT) were at important nodes in the gene network. Among them, the high expression of ADRA1A, PRKG2, CHRM3, ADRA1D and EDN3 significantly extended the DFS of patients with prostate cancer (all P<0.01). Conclusion: ADRA1A, PRKG2, CHRM3, ADRA1D and EDN3 are regulated by key dysregulated transcription factors and highly associated with clinical features of prostate cancer. Their high expressions will significantly prolong the DFS of prostate cancer patients, which may shed light to the discovery of mechanism in prostate adenocarcinoma.

OBJECTIVE: To observe the effects of abdominal acupuncture and the periodic therapy of Chinese herbal medicine on follicular development and endometrial receptivity in the patients with infertility induced by ovulation failure and differentiated as kidney deficiency in TCM. METHODS: A total of 84 patients with infertility induced by ovulation failure and differentiated as kidney deficiency were randomized into a combined therapy group (27 cases), an abdominal acupuncture group (27 cases) and a western medication group (30 cases). In the combined therapy group, abdominal acupuncture and the periodic treatment of Chinese herbal medicine was provided. In the abdominal acupuncture group, the simple abdominal acupuncture therapy was used. In the western medication group, clomiphene citrate (CC) and human chorionic gonadotrophin (HCG) prescribed. The treatment for one menstrual cycle was taken as one session and 3 sessions of treatment were required except the pregnancy. The folicle development, endometrial thickness and morphology, menstrual condition and TCM symptom score were observed before and after treatment in the three groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the ovulation was recovered to different degrees in the three groups. The ovulation rate was 59.3% (16/27) in the combined therapy group, 55.6% (15/27) in the abdominal acupuncture group and 53.3% (16/30) in the western medication group. The difference was not significant in comparison among the three groups (>0.05). After treatment, the endometrial thickness in the periovulatory period was increased as compared with the thickness before treatment in the combined therapy group and the abdominal acupuncture group (both <0.05). After treatment, the endometrial thickness in the combined therapy group was higher than the western medication group (<0.05). In comparison before and after treatment, the difference in the endometrial morphology was significant in the combined therapy group and the abdominal acupuncture group (both <0.05). In comparison between the combined therapy group and the western medication group, the difference in the endometrial morphology was significant after treatment (<0.05). After treatment, the menstrual condition and TCM symptom score in the combined therapy group and the abdominal acupuncture group were all improved as compared with those before treatment (all <0.05). The score of menstrual condition in the combined therapy group was higher than the western medication group (<0.05) and TCM symptom score in the combined therapy group and abdominal acupuncture group was higher than the western medication group after treatment (all <0.05). The total effective rate was 88.9% (24/27) in the combined therapy group and was 92.6% (25/29) in the abdominal acupuncture group, which was higher than 56.7% (17/30) in the western medication group (<0.01). There was no adverse reaction in the combined therapy group and the abdominal acupuncture group. CONCLUSION Abdominal acupuncture combined with the periodic therapy of Chinese herbal medicine improve the menstrual condition and relieve the clinical symptoms of infertility induced by ovulation failure of kidney deficiency in the patients and the therapeutic effects are better than the medication with CC + HCG. This combined therapy improves the ovulation rate and the endometrial receptivity at periovulatory stage to increase the pregnancy rate. There is no adverse reaction discovered in clinical practice.
Acupuncture Therapy ; Clomiphene ; Drugs, Chinese Herbal ; Female ; Humans ; Infertility, Female ; Ovulation ; Pregnancy

OBJECTIVE To evaluate the clinical value of contrast-enhanced ultrasonography (CEUS) in diagnosing thyroid carcinoma.METHODS The clinical data of 129 patients with thyroid nodules,who were examined by CEUS and were operated in Xinhua Hospital between Jan 2014 and Aug 2015,were analyzed in order to compare the diagnostic results of CEUS to the postoperative pathologic findings,and to summarize its imaging features.RESULTS A total of 132 thyroid nodules in 129 patients were examined by CEUS.Among them,103 nodules were diagnosed as thyroid carcinoma,24 nodules were benign thyroid tumor and 5 nodules were thyroiditis.Compared with pathology results,the diagnostic accuracy,sensitivity and specificity of contrast-enhanced ultrasound is 88.6％,92.2％ and of 75.9％ respectively.The diagnosis of the CEUS in 31 cases was not consistent with the pathological results,in which 8 cases of thyroid carcinoma were misdiagnosed as benign tumor,3 cases of thyroiditis were misdiagnosed as thyroid carcinoma,and 20 cases of benign tumors were misdiagnosed as thyroid carcinoma.The malignant thyroid nodules mainly were papillary carcinoma,which was characterized by'low enhanced'and'slow in fast out'performance in the contrast-enhanced ultrasound examination.CONCLUSION The contrast-enhanced ultrasound examination in diagnosing thyroid carcinoma has much more specificity and sensitivity,the'low-enhanced'and'slow in fast out'signs of the CEUS were the important features of malignant thyroid nodules.

OBJECTIVETo investigate the expression patterns of osterix in the early stage of cranio-maxillofacial developmental in zebrafish and to prepare for a further research of osterix gene in bone and tooth development.

METHODSThe osterix templates were amplified by PCR to generate DIG labeled antisense and sense probes. Whole mount in situ hybridization was used to analyze the expression patterns of osterix in the early stage cranio-maxillofacial development of zebrafish. The expression patterns of osterix gene in mineralization progresses of cranial and maxillofacial bones were compared. The osterix gene expression in tooth development and mineralization was highlighted by alizarin red staining.

RESULTSSpecific DIG labeled probes of osterixwere synthesized successfully. The whole mount in situ hybridization showed that the osterix expression was in the intramembranous ossification at 3 days post fertilization(dpf) and 4 dpf. The specific osterix expression in tooth at 5 dpf and 6 dpf were also observed. The sense probe served as a negative control. Osterix expressed in the unmineralized early bone matrix, the tooth matrix of the primary tooth(3V(1), 5V(1)) and the first replacement tooth(4V(2)).

CONCLUSIONSOur findings showed that osterix might play roles in the process of the early mineralized bone matrix changing into the late mature mineralized bone matrix and the process of development and mineralization of tooth crown matrix.

Animals ; Calcification, Physiologic ; genetics ; Gene Expression ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Maxillofacial Development ; genetics ; Osteogenesis ; genetics ; Sp7 Transcription Factor ; Tooth ; metabolism ; Transcription Factors ; genetics ; metabolism ; Zebrafish ; Zebrafish Proteins ; genetics ; metabolism