ObjectiveTo observe the effectiveness and safety of Jiuzihuichun decoction combined with spleen- strengthening moxibustion in patients with asthenospermia infertility with spleen-kidney deficiency pattern. MethodsA total of 82 patients with asthenospermia of spleen-kidney deficiency pattern in Shanghai Seventh People's Hospital were included. The patients were randomly divided into an observation group and a control group， with 41 patients in each group. The control group received oral administration of WuziYanzong pills combined with spleen-strengthening moxibustion. The dosage of Wuzi Yanzong pills was 1 bag each time， and it was taken twice a day. The spleen-strengthening moxibustion was carried out once a week. The observation group， on the other hand， took Jiuzi Huichun decoction orally combined with spleen-strengthening moxibustion. The Jiuzi Huichun Decoction was taken 200 mL each time， twice a day， with one dose in the morning and one in the evening. The spleen-strengthening moxibustion for the observation group was also performed once a week. The treatment course for both groups was 12 weeks， and they were followed up for an additional 12 weeks. During the treatment process，12 cases were either lost to follow-up or excluded. Eventually， 70 cases were available for evaluation，with 35 cases in the control group and 35 cases in the observation group. The pregnancy status of the patients' spouse within 6 months was recorded. The traditional Chinese medicine （TCM） syndrome scores of spleen-kidney deficiency pattern before and after treatment were evaluated. The semen volume，semen routine parameters，normal sperm morphology，sperm DNA fragmentation index，seminal plasma fructose，seminal plasma acid phosphatase， and seminal plasma α-glucosidase levels of the two groups were detected before and after treatment. In addition， the safety indicators related to liver and kidney functions of the two groups were detected before and after treatment. ResultsDuring the 6-month observation period， when compared with the situation before treatment in their respective groups，the semen volume of the observation group and the control group increased. In contrast， the sperm concentration，sperm motility，proportion of a+b-grade sperm，normal sperm morphology，seminal plasma fructose，seminal plasma acid phosphatase，seminal plasma α-Glucosidase，the proportion of a-grade sperm，linear sperm motility，linear sperm concentration， and linear sperm count all increased significantly（P<0.05）. At the same time， the sperm DNA fragmentation index and the TCM syndrome scores of the spleen-kidney deficiency pattern decreased significantly（P<0.05）. When the observation group was compared with the control group after treatment， the clinical efficacy of the observation group was better（Z=-2.276，P<0.05）. The pregnancy rate of the observation group's spouses was 14.3%，which was higher than the 2.9% of the control group. The sperm motility， the proportion of a+b-grade sperm，seminal plasma fructose，the proportion of a-grade sperm，normal sperm morphology，α-glucosidase， and linear sperm motility in the observation group were higher than those in the control group （P<0.05）. Moreover， the sperm DNA fragmentation index and the TCM syndrome scores of spleen-kidney deficiency pattern in the observation group were lower than those in the control group （P<0.01）. No serious adverse reactions occurred in the two groups，and no abnormalities were found in the safety indicators after treatment. ConclusionJiuzi Huichun decoction combined with spleen-strengthening moxibustion can enhance sperm viability and sperm concentration. It can also improve the TCM-related symptoms of asthenospermia of spleen-kidney deficiency pattern and sperm morphology. Additionally， it can reduce the sperm DNA fragmentation index and regulate the level of seminal plasma bioenzyme in patients with male asthenospermia infertility of spleen-kidney deficiency pattern. Therefore， it is worthy of further promotion and application in clinical practice.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Objective To explore the relationship between the M1/M2 macrophages and severity of diabetic retinopathy(DR).Methods This retrospective study included 42 patients with or without DR who had type 2 diabetes mellitus(T2DM)and 19 healthy individuals undergoing cataract intraocular surgery without systemic or ocular diseases from Handan Central Hospital between April 2022 and November 2023.Patients with T2DM were divided into three groups:diabetes mellitus with non-dominant diabetic retinopathy(T2DM non-DR group,n=20),mild and moderate non-proliferative diabetic retinopathy(NPDR)(n=10)and severe NPDR/proliferative diabetic retinopathy(PDR)(n=12).Peripheral blood and aqueous humor were obtained at surgery initiation.The levels of VEGF-A,IL-8,Elafin and TGF-β in the samples were analyzed using kits,and the ratio of M1 macrophages to M2 macrophages was analyzed by flow cytometry.Results Among patients with T2DM,there were significant differences in the duration of diabetes,insulin and metformin use among the three groups(P<0.05).Aqueous humor levels of VEGF-A,IL-8,Elafin,M1 ratio,M2 ratio and TGF-β of each group were significantly different(F=17.40,9.492,4.792,11.32,5.768 and 20.38,all P<0.01).The levels of VEGF-A,IL-8,Elafin,M1 ratio,VD86 and TGF-β in severe NPDR/PDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05),and the levels of VEGF-A,IL-8 and Elafin in severe NPDR/PDR group were significantly higher than those in mild and moderate NPDR group(P<0.05).The levels of M1 proportion and TGF-β in aqueous humor of the mild to moderate NPDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05).The level of M1 in aqueous humor was positively correlated with the levels of M2,Elafin,TGF-β and VEGF-A(r=0.260,0.411,0.726 and 0.304,all P<0.05),and the level of M2 was positively correlated with the levels of Elafin and TGF-β(r=0.865,0.552,all P<0.01).Conclusion The elevation of IL-8 and M1 macrophages in the aqueous humor may promote the occurrence of DR,while the increase of Elafin and M2 macrophages may be a compensatory regulation to chronic inflammation,which is involved in the regulation of local microvascular lesions and fibrosis.

AIM: To explore the variance in efficacy between botulinum toxin A(BTA)injection and extraocular muscle surgery in managing large-angle(≥+60 PD)acute acquired concomitant esotropia(AACE).METHODS: A retrospective analysis was conducted on clinical data of 60 patients with AACE treated at our hospital from June 2020 to December 2022. Patients were divided into three groups based on different treatments: 2.5 IU BTA injection group(14 cases), 5.0 IU BTA injection group(29 cases), and surgical group(17 cases). Follow-up was conducted for 6 mo after treatment to observe the degree of strabismus after the correction of refractive error, visual function, treatment effectiveness, and occurrence of complications after BTA injection.RESULTS: At 6 mo post-treatment, the degree of strabismus in the surgical group and the 5.0 IU BTA injection group was lower than that in the 2.5 IU BTA injection group(P<0.017). However, there was no significant difference in the degree of strabismus between the surgical group and the 5.0 IU BTA injection group(P>0.017). The effective rate of the 5.0 IU BTA injection group was higher than that of the 2.5 IU BTA injection group(86% vs 43%, P<0.017). There was no difference in visual function among the three groups(P>0.05). The incidence of complications after treatment was not significantly different between the 2.5 IU BTA injection group and the 5.0 IU BTA injection group(43% vs 52%, P>0.05).CONCLUSION: For AACE patients with esotropia degree ≥+60 PD, bilateral medial rectus injection of 5.0 IU BTA can yield outcomes comparable to traditional extraocular muscle surgery, with the advantages of minimal trauma and simple and convenient operation.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.

Objective:To evaluate the developmental toxicity of Cry1Ab protein by studying its effects on cell proliferation and differentiation ability using a developmental toxicity assessment model based on embryonic stem-cell.Methods:Cry1Ab protein was tested in seven dose groups(31.25,62.50,125.00,250.00,320.00,1 000.00,and 2 000.00 μg/L)on mouse embryonic stem cells D3(ES-D3)and 3T3 mouse fibroblast cells,with 5-fluorouracil(5-FU)used as the positive control and phos-phate buffer saline(PBS)as the solvent control.Cell viability was detected by CCK-8 assay to calculate the 50％inhibitory concentration(IC50)of the test substance for different cells.Additionally,Cry1 Ab protein was tested in five dose groups(125.00,250.00,320.00,1 000.00,and 2 000.00 μg/L)on ES-D3 cells,with PBS as the solvent control and 5-FU used for model validation.After cell treatment,cardiac differentiation was induced using the embryonic bodies(EBs)culture method.The growth of EBs was observed under a microscope,and their diameters on the third and fifth days were measured.The proportion of EBs differentiating into beating cardiomyocytes was recorded,and the 50％inhibition con-centration of differentiation(ID50)was calculated.Based on a developmental toxicity discrimination func-tion,the developmental toxicity of the test substances was classified.Furthermore,at the end of the cul-ture period,mRNA expression levels of cardiac differentiation-related markers(Oct3/4,GATAA-4,Nkx2.5,and β-MHC)were quantitatively detected using real-time quantitative polymerase chain reaction(qPCR)in the collected EBs samples.Results:The IC50 of 5-FU was determined as 46.37 μg/L in 3T3 cells and 32.67 μg/L in ES-D3 cells,while the ID50 in ES-D3 cells was 21.28 μg/L.According to the discrimination function results,5-FU was classified as a strong embryotoxic substance.There were no sta-tistically significant differences in cell viability between different concentrations of Cry 1 Ab protein treat-ment groups and the control group in both 3T3 cells and ES-D3 cells(P＞0.05).Moreover,there were no statistically significant differences in the diameter of EBs on the third and fifth days,as well as their morphology,between the Cry1Ab protein treatment groups and the control group(P＞0.05).The cardi-ac differentiation rate showed no statistically significant differences between different concentrations of Cry1Ab protein treatment groups and the control group(P＞0.05).5-FU significantly reduced the mRNA expression levels of β-MHC,Nkx2.5,and GATA-4(P＜0.05),showing a dose-dependent trend(P＜0.05),while the mRNA expression levels of the pluripotency-associated marker Oct3/4 exhibited an increasing trend(P＜0.05).However,there were no statistically significant differences in the mRNA expression levels of mature cardiac marker β-MHC,early cardiac differentiation marker Nkx2.5 and GATA-4,and pluripotency-associated marker Oct3/4 between the Cry1Ab protein treatment groups and the control group(P＞0.05).Conclusion:No developmental toxicity of Cry1Ab protein at concen-trations ranging from 31.25 to 2 000.00 μg/L was observed in this experimental model.

Objective To explore the CT imaging features of renal mucinous tubular and spindle cell carcinoma(MTSCC).Methods The CT images of 9 cases patients with renal MTSCC confirmed by pathology were analyzed retrospectively,and their size,shape,density,degree of enhancement and enhancement mode were analyzed.Results There were 6 cases of left renal and 3 cases of right renal,with the largest diameter ranging from 1.6 cm to 7.7 cm.The shape of renal MTSCC was round in 4 cases,oblong in 3 cases,and fan-shaped in 2 cases.The long axis of the oblong tumor was parallel to the renal column,the central angle of the fan-shaped tumor was located in the renal medulla,and the arc was located under the renal capsule.Renal MTSCC was mainly located in the renal medulla.There were 6 cases of complete endophytic tumors,5 of which compressed the renal sinus.The tumor density was uniform in 5 cases,and the CT value of the solid component of the tumor was(32.43±4.82)HU,and the difference was not statistically significant compared with that of the renal parenchymal density(P=0.859).After enhancement,the solid component of the tumor showed mild uniform enhancement in the cortical phase,with a CT value of(41.71±6.74)HU.In the parenchymal phase and excretory phase,there was progressive enhancement,and the CT values were(58.23±9.42)HU and(61.81±9.49)HU,respectively.The CT value of each phase of tumor after enhancement was lower than that of renal medulla in the same period,and the differences were statisti-cally significant(P=0.001,P=0.005,P=0.002).Conclusion Renal MTSCC is mainly located in the renal medulla,which is easy to compress the renal sinus.It can be oblong or fan-shaped.Cystic,necrosis and calcification are rare.After enhancement,the tumor shows mild uniform enhancement in the cortical phase,progressive enhancement in the parenchymal phase and the excretory phase,and the CT value of each phase are lower than that of the renal medulla in the same period,which can suggest the diagnosis.