Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective:To evaluate the diagnostic value of micro flow imaging (MFI) supported by Image Pro Plus (IPP) software for BI-RADS classification of breast nodules and the correlation between its parameters and Ki-67 expression level.Methods:A total of 205 cases of breast solid nodules with ultrasound BI-RADS classification of 4 categories were enrolled in this study. BI-RADS classification, CDFI score, MFI score, CDFI-IPP score and MFI-IPP score by IPP software were performed for each nodule. Ki-67 immunohistochemical staining of invasive ductal carcinoma was performed to analyze the correlation between MFI-IPP-VI and Ki-67 expression levels.Results:The combined BI-RADS classification for diagnosis of malignant nodules had the largest area under the ROC curve, which was significantly higher than that of BI-RADS, MFI-IPP-VI, MFI score, CDFI-IPP-VI, and CDFI score (all P<0.05). The combined BI-RADS classification had the best diagnostic efficacy for the diagnosis of malignant nodules with a sensitivity of 96.4%, specificity of 65.6% and accuracy of 82.4%. In addition, the agreement between experienced and inexperienced sonographers applying MFI-IPP-VI was higher than MFI (Kappa=0.780 vs. Kappa=0.743). The mean value of Ki-67 in invasive ductal carcinoma was 21.93%±16.37%, and Spearman's correlation analysis showed a positive correlation between MFI-IPP-VI and Ki-67 expression level ( r=0.815, P<0.05). Conclusions:MFI-IPP can assist sonographers to classify breast nodules by BI-RADS, providing an effective basis for puncture biopsy. MFI-IPP-VI offers the possibility of noninvasively predicting the expression level of Ki-67 in invasive ductal carcinoma.

Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.

Objective To establish a model of radiation-induced myocardial fibrosis in mice, and study the effect of TGF-β/SMAD pathway on radiation-induced myocardial fibrosis in mice and the protective effect of pirfenidone capsules (PFD) on radiation-induced myocardial fibrosis. Methods Male C57BL/6J mice were randomly divided into control group, irradiation group, and drug intervention groups (low-dose PFD + irradiation group and high-dose PFD + irradiation group). After radiation exposure, the control group and the irradiation group were given sodium carboxymethyl cellulose by gavage, while the low-dose PFD + irradiation group and the high-dose PFD + irradiation group were given PFD at 150 and 300 mg/kg daily by gavage for 12 consecutive weeks, respectively. The body weights of mice were measured and recorded weekly. The pathological changes of heart tissues in mice were observed by H&E and Masson’s trichrome staining. The expression levels of TGF-β, SMAD2, and SMAD3 mRNAs in mouse heart tissues were detected by RT-PCR. The expression levels of TGF-β, SMAD2, and SMAD3 proteins in mouse heart tissues were detected by Western blot. The expression levels of CK and CK-MB in mouse heart tissues were detected by blood biochemical tests. Results H&E and Masson’s trichrome staining showed severe myocardial fibrosis in the irradiation group compared with the control group. Compared with the irradiation group, the two groups with drug intervention showed reduced heart disease and myocardial fibrosis. RT-PCR and Western blot showed that the expression levels of TGF-β, SMAD2, and SMAD3 were up-regulated in the irradiation group compared with the other three groups (P < 0.05). The expression levels of TGF-β, SMAD2, and SMAD3 were down-regulated in the two groups treated with PFD compared with the irradiation group (P < 0.05). The expression levels of CK and CK-MB in mouse heart tissues were down-regulated in the two groups treated with PFD compared to irradiation group (P < 0.05). Conclusion Radiation has long-term effects on normal heart tissue, causing myocardial damage and promoting myocardial fibrosis. The up-regulation of TGF-β/SMAD pathway is related to the formation of radiation-induced myocardial fibrosis. PFD can mitigate the progression of myocardial fibrosis and protect heart tissue by down-regulating TGF-β/SMAD pathway.

Objective To investigate application value of three-dimensional light sheet microscopy imaging for evaluating intraplaque neovascularization in arterial plaques and the efficacy of intervention,and to assess the effect of melatonin(MLT)on neovascularization by these means.Methods Thirty-six ApoE-/-model mice were randomly divided into three groups(n=12):vehicle group,MLT group,and MLT+GW9662 intervention group(MLT+GW).The mice were treated with vehicle,MLT alone,or MLT combined with peroxisome proliferator activated receptor-γ(PPARγ)inhibitor GW9662,respectively.The carotid arteries of the models were three-dimensionally imaged using a light sheet microscopy,and the length,volume and other indicators of neovascularization were quantitatively analyzed using Imaris software.Subsequently,CD31 immunohistochemical staining was performed for verification.Results The light sheet microscopy preliminarily achieved the three-dimensional visualization of intraplaque neovascularization,and its structure was observed to be three-dimensionally reticular and scattered.The results of Imaris quantitative analysis showed that,compared with vehicle group,the total intraplaque neovas cularization length in the MLT group was shortened[(15.79±12.90)mm vs.(33.42±11.16)mm,P<0.05],the total volume was reduced[(1.34±1.47)×10-3 mm3 vs.(13.44±7.35)×10-3 mm3,P<0.05],and the volume ratio was decreased(0.44%±0.47%vs.3.76%±1.74%,P<0.05).The above indicators in MLT+GW group were significantly increased compared with those in MLT group[total length:(35.31±4.69)mm,total volume:(8.87±3.46)×10-3 mm3,volume ratio:2.89%±0.38%;P<0.05].The CD31 immunohistochemical staining also supported the above findings(P<0.05).Conclusions Based on the light sheet microscopy imaging technology,the three-dimensional visualization and quantitative analysis of intraplaque neovascularization were preliminarily realized.It was found that MLT could reduce the overall burden of intraplaque neovascularization,and PPARγ might be involved in its regulatory process.

Objective To evaluate the value of pre-ascent 6-minute walking test performed at a high altitude in predicting the incidence of acute mountain sickness(AMS)induced by rapid ascent to a very high altitude.Methods After baseline information was collected,participants completed the 6-minute walking test at a high altitude of 2 900 m.Then,they rapidly ascended to a very high altitude of 5 000 m.The Lake Louise score was recorded to assess AMS.Results The AMS group showed a shorter pre-ascent 6-minute walking distance(6MWD)at the high altitude than the non-AMS group[480.00(450.00,521.75)m vs.546.00(516.50,568.50)m,P=0.006].No difference was observed regarding the pre-ascent heart rate or peripheral oxygen saturation(both P>0.05).The pre-ascent 6MWD at the high altitude was negatively correlated with the Lake Louise score assessed after rapid ascent to the very high altitude(r=-0.497,P=0.012).Logistic regression analysis confirmed that the pre-ascent 6MWD at the high altitude was associated with the risk of AMS induced by rapid ascent to the very high altitude(OR=0.971,95% CI=0.947-0.996,P=0.022).The results indicated that the pre-ascent 6MWD demonstrated ideal prediction performance(area under receiver operating characteristic curve=0.846,P=0.006).Conclusion The pre-ascent 6MWD recorded at the high altitude is a convenient and reliable predictor of the AMS induced by rapid ascent to the very high altitude.
Humans ; Altitude Sickness/diagnosis* ; Male ; Adult ; Female ; Young Adult ; Middle Aged ; Acute Disease ; Walk Test ; Walking ; Altitude ; Exercise Test

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To evaluate the feasibility and safety of open ventilation masks in patients with proliferative diabetic retinopathy (PDR) undergoing vitrectomy under local anesthesia.Methods:A randomized clinical trial was conducted.Eighty PDR patients (80 eyes) undergoing vitrectomy with local anesthesia were enrolled at Xuzhou Municipal Hospital from May to July 2024.Patients were randomly divided into an experimental group and a control group using a random number table method, with 40 cases (40 eyes) in each group.The experimental group received oxygen through an ophthalmic surgical open ventilation mask during the operation, while the control group used a traditional nasal cannula.The respiratory rate, heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation before and after oxygen inhalation during the operation were compared between the two groups.Patient comfort level, airway patency, anxiety status, satisfaction level, operation time, surgical success rate, and incidence of intraoperative complications were also compared.This study adhered to the Declaration of Helsinki and the study protocol was appreed by the Ethics Committee of Xuzhou Municipal Hospital (No.2024-KY-065).Results:After oxygen inhalation during the operation, improvements in respiratory rate, heart rate, and oxygen saturation were greater in the experimental group than in the control group, with statistically significant differences ( t=4.671, 7.894, 1.588; all P<0.05).The Borg, and Hamilton Anxiety Scale scores were lower in the experimental group than in the control group, with statistically significant differences ( t=2.828, 4.880; both P<0.05), while the Bruggrmann Comfort Scale score was higher than that in the control group ( t=2.774, P<0.05).There were no statistically significant differences in operation time, surgical success rate or incidence of complications between the two groups ( t=0.595, P=0.554; χ2=0.346, 0.263; both P>0.05).Satisfaction rate of patients in the experimental group was 97.5%(39/40), which was higher than 85.0%(34/40) in the control group, with a statistically significant difference ( χ2=3.914, P=0.048). Conclusions:For PDR patients undergoing vitreous surgery under local anesthesia, using an ophthalmic surgical open ventilation mask for oxygen inhalation can effectively enhance respiratory comfort level, alleviate anxiety, maintain stable vital signs, improve overall comfort level, and ensure smooth surgery, without observed adverse reactions related to mask use, which makes it worthy of clinical promotion and application.

Objective:To evaluate the feasibility and safety of open ventilation masks in patients with proliferative diabetic retinopathy (PDR) undergoing vitrectomy under local anesthesia.Methods:A randomized clinical trial was conducted.Eighty PDR patients (80 eyes) undergoing vitrectomy with local anesthesia were enrolled at Xuzhou Municipal Hospital from May to July 2024.Patients were randomly divided into an experimental group and a control group using a random number table method, with 40 cases (40 eyes) in each group.The experimental group received oxygen through an ophthalmic surgical open ventilation mask during the operation, while the control group used a traditional nasal cannula.The respiratory rate, heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation before and after oxygen inhalation during the operation were compared between the two groups.Patient comfort level, airway patency, anxiety status, satisfaction level, operation time, surgical success rate, and incidence of intraoperative complications were also compared.This study adhered to the Declaration of Helsinki and the study protocol was appreed by the Ethics Committee of Xuzhou Municipal Hospital (No.2024-KY-065).Results:After oxygen inhalation during the operation, improvements in respiratory rate, heart rate, and oxygen saturation were greater in the experimental group than in the control group, with statistically significant differences ( t=4.671, 7.894, 1.588; all P<0.05).The Borg, and Hamilton Anxiety Scale scores were lower in the experimental group than in the control group, with statistically significant differences ( t=2.828, 4.880; both P<0.05), while the Bruggrmann Comfort Scale score was higher than that in the control group ( t=2.774, P<0.05).There were no statistically significant differences in operation time, surgical success rate or incidence of complications between the two groups ( t=0.595, P=0.554; χ2=0.346, 0.263; both P>0.05).Satisfaction rate of patients in the experimental group was 97.5%(39/40), which was higher than 85.0%(34/40) in the control group, with a statistically significant difference ( χ2=3.914, P=0.048). Conclusions:For PDR patients undergoing vitreous surgery under local anesthesia, using an ophthalmic surgical open ventilation mask for oxygen inhalation can effectively enhance respiratory comfort level, alleviate anxiety, maintain stable vital signs, improve overall comfort level, and ensure smooth surgery, without observed adverse reactions related to mask use, which makes it worthy of clinical promotion and application.