Objective:To detect the expression of Silent Information Regulator 1 (SIRT1), phosphorylated P53 protein (P53 protein), and Survivin in pancreatic cancer tissues, and to analyze their relationship with the prognosis of pancreatic cancer.Methods:A retrospective analysis was conducted on the clinical data of 102 patients with pancreatic cancer admitted to the Affiliated Hospital of Yan'an University from January 2020 to January 2023. The expression levels of SIRT1, P53, and Survivin in pancreatic cancer tissues and adjacent non-cancerous tissues were determined. Patients were followed up for 12-18 months and were divided into a survival group ( n = 59 and a death group ( n = 43) based on their survival status. The relationship between the expression of SIRT1, P53, and Survivin and the patients' pathological characteristics and prognosis was analyzed. Results:The positive expression rates of SIRT1, P53, and Survivin in pancreatic cancer tissues were 66.67% (68/102), 71.57% (73/102), and 73.53% (75/102), respectively, all of which were significantly higher than the rates in adjacent non-cancerous tissues, which were 26.47% (27/102), 29.41% (30/102), and 31.37% (32/102) ( χ2 = 33.11, 36.25, 36.34, all P < 0.001). Among patients with tumor stages Ⅱ-Ⅲ, low differentiation, and lymphatic metastasis, the positive rates of SIRT1 [82.61% (38/46), 76.06% (54/71), 81.82% (27/33)], P53 [84.78% (39/46), 80.28% (57/71), 87.88% (29/33)], and Survivin [86.96% (40/46), 81.69% (57/71), 87.88% (29/33)] were significantly higher than those in patients with tumor stage Ⅰ, moderate to high differentiation, and without lymphatic metastasis [SIRT1: 53.57% (30/56), 45.16% (14/31), 59.42% (41/69); P53: 60.71% (34/56), 51.61% (16/31), 63.77% (44/96); Survivin: 62.50% (35/56), 54.84% (17/31), 66.67% (46/96), χ2 SIRT1 = 9.58, 9.26, 5.04; χ2 P53 = 7.19, 8.71, 6.37; χ2 Survivin = 11.36, 7.99, 5.16, all P < 0.05]. The survival rates of patients with positive expression of SIRT1, P53, and Survivin in cancer tissues were 47.06% (32/68), 49.32% (36/73), and 49.33% (37/75), respectively, all of which were lower than the survival rates of patients with negative expression of SIRT1, P53, and Survivin, which were 79.40% (27/34), 79.31% (23/29), and 81.48% (22/27) (Log Rank χ2 = 8.79, 10.98, 12.65, all P < 0.05). In the survival group, the proportions of patients with tumor stages Ⅱ-Ⅲ, low differentiation, lymphatic metastasis, and positive expression of SIRT1, P53, and Survivin were 45.65% (21/46), 49.30% (35/71), 39.39% (13/33), 47.06% (32/68), 49.32% (36/73), and 49.33% (37/75), all of which were lower than the corresponding rates in patients with tumor stage Ⅰ, moderate to high differentiation, no lymphatic metastasis, and negative expression of SIRT1, P53, and Survivin, which were 67.86% (38/56), 77.42% (24/31), 66.67% (46/69), 79.41% (27/34), 79.31% (23/29), and 81.48% (22/27) ( χ2 = 5.10, 6.99, 6.80, 9.73, 7.65, 8.41, all P < 0.05). Tumor stage Ⅱ-Ⅲ ( OR = 2.413), low differentiation ( OR = 3.527), lymphatic metastasis ( OR = 3.077), positive SIRT1 expression ( OR = 4.339), positive P53 expression ( OR = 3.940), and positive Survivin expression ( OR = 4.519) were all identified as risk factors for poor prognosis in patients with pancreatic cancer (all P < 0.05). Conclusions:The expression of SIRT1, P53, and Survivin in the cancer tissues of patients with pancreatic cancer is closely associated with tumor stage, differentiation, and lymphatic metastasis. Additionally, the expression levels of SIRT1, P53, and Survivin are all significant factors influencing patient prognosis. Monitoring their expression can aid in the clinical prediction of patient outcomes.

Objective:To detect the expression of Silent Information Regulator 1 (SIRT1), phosphorylated P53 protein (P53 protein), and Survivin in pancreatic cancer tissues, and to analyze their relationship with the prognosis of pancreatic cancer.Methods:A retrospective analysis was conducted on the clinical data of 102 patients with pancreatic cancer admitted to the Affiliated Hospital of Yan'an University from January 2020 to January 2023. The expression levels of SIRT1, P53, and Survivin in pancreatic cancer tissues and adjacent non-cancerous tissues were determined. Patients were followed up for 12-18 months and were divided into a survival group ( n = 59 and a death group ( n = 43) based on their survival status. The relationship between the expression of SIRT1, P53, and Survivin and the patients' pathological characteristics and prognosis was analyzed. Results:The positive expression rates of SIRT1, P53, and Survivin in pancreatic cancer tissues were 66.67% (68/102), 71.57% (73/102), and 73.53% (75/102), respectively, all of which were significantly higher than the rates in adjacent non-cancerous tissues, which were 26.47% (27/102), 29.41% (30/102), and 31.37% (32/102) ( χ2 = 33.11, 36.25, 36.34, all P < 0.001). Among patients with tumor stages Ⅱ-Ⅲ, low differentiation, and lymphatic metastasis, the positive rates of SIRT1 [82.61% (38/46), 76.06% (54/71), 81.82% (27/33)], P53 [84.78% (39/46), 80.28% (57/71), 87.88% (29/33)], and Survivin [86.96% (40/46), 81.69% (57/71), 87.88% (29/33)] were significantly higher than those in patients with tumor stage Ⅰ, moderate to high differentiation, and without lymphatic metastasis [SIRT1: 53.57% (30/56), 45.16% (14/31), 59.42% (41/69); P53: 60.71% (34/56), 51.61% (16/31), 63.77% (44/96); Survivin: 62.50% (35/56), 54.84% (17/31), 66.67% (46/96), χ2 SIRT1 = 9.58, 9.26, 5.04; χ2 P53 = 7.19, 8.71, 6.37; χ2 Survivin = 11.36, 7.99, 5.16, all P < 0.05]. The survival rates of patients with positive expression of SIRT1, P53, and Survivin in cancer tissues were 47.06% (32/68), 49.32% (36/73), and 49.33% (37/75), respectively, all of which were lower than the survival rates of patients with negative expression of SIRT1, P53, and Survivin, which were 79.40% (27/34), 79.31% (23/29), and 81.48% (22/27) (Log Rank χ2 = 8.79, 10.98, 12.65, all P < 0.05). In the survival group, the proportions of patients with tumor stages Ⅱ-Ⅲ, low differentiation, lymphatic metastasis, and positive expression of SIRT1, P53, and Survivin were 45.65% (21/46), 49.30% (35/71), 39.39% (13/33), 47.06% (32/68), 49.32% (36/73), and 49.33% (37/75), all of which were lower than the corresponding rates in patients with tumor stage Ⅰ, moderate to high differentiation, no lymphatic metastasis, and negative expression of SIRT1, P53, and Survivin, which were 67.86% (38/56), 77.42% (24/31), 66.67% (46/69), 79.41% (27/34), 79.31% (23/29), and 81.48% (22/27) ( χ2 = 5.10, 6.99, 6.80, 9.73, 7.65, 8.41, all P < 0.05). Tumor stage Ⅱ-Ⅲ ( OR = 2.413), low differentiation ( OR = 3.527), lymphatic metastasis ( OR = 3.077), positive SIRT1 expression ( OR = 4.339), positive P53 expression ( OR = 3.940), and positive Survivin expression ( OR = 4.519) were all identified as risk factors for poor prognosis in patients with pancreatic cancer (all P < 0.05). Conclusions:The expression of SIRT1, P53, and Survivin in the cancer tissues of patients with pancreatic cancer is closely associated with tumor stage, differentiation, and lymphatic metastasis. Additionally, the expression levels of SIRT1, P53, and Survivin are all significant factors influencing patient prognosis. Monitoring their expression can aid in the clinical prediction of patient outcomes.

OBJECTIVE:To assess the efficacy and safety of transcranial magnetic stimulation in the treatment of refractory depression and to compare the differences in efficacy between various transcranial magnetic stimulation treatment protocols in refractory depression,thereby providing a theoretical basis for the clinical selection of transcranial magnetic stimulation treatment protocols.METHODS:A comprehensive search was conducted across multiple databases,including PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,CBM and VIP.The search terms were"transcranial magnetic stimulation,treatment-resistant depression,randomized controlled trial"in Chinese,and"depressive disorder,treatment-resistant,transcranial magnetic stimulation,randomized controlled trial"in English.The objective was to identify randomized controlled trials on the treatment of patients with refractory depression published from the establishment of the databases to September 2024.The quality of the included studies was evaluated using the Cochrane risk of bias assessment tool,version 5.1.0,and the Physiotherapy Evidence Database scale.Meta-analysis of the outcome indicators was conducted using the Review Manager 5.4 and Stata 18.0 software.RESULTS:(1)Following a comprehensive review,20 randomized controlled trials were included in the analysis.All of the trials were assessed to be of high or very high quality according to the Physiotherapy Evidence Database scale.(2)Meta-analysis results showed that,compared with the sham stimulation group,high-frequency repetitive transcranial magnetic stimulation could significantly reduce the scores of Hamilton Depression Rating Scale[mean difference(MD)=-3.89,95％confidence interval(CI):-6.14 to-1.65,P＜0.05)or the Montgomery Depression Rating Scale(MD=-3.97,95％CI:-6.57 to-1.36,P＜0.05).(3)The probability ranking results of the network Meta-analysis showed that,in terms of the Hamilton Depression Rating Scale score,the probability ranking results were as follows:high-frequency repetitive transcranial magnetic stimulation(69.9％)＞intermittent theta burst stimulation(62.8％)＞bilateral theta pulse stimulation(57.5％)＞low-frequency repetitive transcranial magnetic stimulation(54.9％)＞bilateral sequential transcranial magnetic stimulation(49.0％)＞transcranial pulsed electromagnetic field(37.0％)＞sham stimulation(18.9％).And in terms of the Montgomery Depression Rating Scale score,the probability ranking results were as follows:high-frequency repetitive transcranial magnetic stimulation(93.3％)＞bilateral theta pulse stimulation(50.3％)＞sham stimulation(45.9％)＞low-frequency repetitive transcranial magnetic stimulation(32.1％)＞bilateral sequential transcranial magnetic stimulation(28.4％).CONCLUSION:Transcranial magnetic stimulations can improve the depressive symptoms of patients with treatment-resistant depression.Among them,the high-frequency repetitive transcranial magnetic stimulation mode has the best effect on improving the depressive symptoms of patients with treatment-resistant depression,followed by the intermittent θ burst stimulation mode.

OBJECTIVE:To assess the efficacy and safety of transcranial magnetic stimulation in the treatment of refractory depression and to compare the differences in efficacy between various transcranial magnetic stimulation treatment protocols in refractory depression,thereby providing a theoretical basis for the clinical selection of transcranial magnetic stimulation treatment protocols.METHODS:A comprehensive search was conducted across multiple databases,including PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,CBM and VIP.The search terms were"transcranial magnetic stimulation,treatment-resistant depression,randomized controlled trial"in Chinese,and"depressive disorder,treatment-resistant,transcranial magnetic stimulation,randomized controlled trial"in English.The objective was to identify randomized controlled trials on the treatment of patients with refractory depression published from the establishment of the databases to September 2024.The quality of the included studies was evaluated using the Cochrane risk of bias assessment tool,version 5.1.0,and the Physiotherapy Evidence Database scale.Meta-analysis of the outcome indicators was conducted using the Review Manager 5.4 and Stata 18.0 software.RESULTS:(1)Following a comprehensive review,20 randomized controlled trials were included in the analysis.All of the trials were assessed to be of high or very high quality according to the Physiotherapy Evidence Database scale.(2)Meta-analysis results showed that,compared with the sham stimulation group,high-frequency repetitive transcranial magnetic stimulation could significantly reduce the scores of Hamilton Depression Rating Scale[mean difference(MD)=-3.89,95％confidence interval(CI):-6.14 to-1.65,P＜0.05)or the Montgomery Depression Rating Scale(MD=-3.97,95％CI:-6.57 to-1.36,P＜0.05).(3)The probability ranking results of the network Meta-analysis showed that,in terms of the Hamilton Depression Rating Scale score,the probability ranking results were as follows:high-frequency repetitive transcranial magnetic stimulation(69.9％)＞intermittent theta burst stimulation(62.8％)＞bilateral theta pulse stimulation(57.5％)＞low-frequency repetitive transcranial magnetic stimulation(54.9％)＞bilateral sequential transcranial magnetic stimulation(49.0％)＞transcranial pulsed electromagnetic field(37.0％)＞sham stimulation(18.9％).And in terms of the Montgomery Depression Rating Scale score,the probability ranking results were as follows:high-frequency repetitive transcranial magnetic stimulation(93.3％)＞bilateral theta pulse stimulation(50.3％)＞sham stimulation(45.9％)＞low-frequency repetitive transcranial magnetic stimulation(32.1％)＞bilateral sequential transcranial magnetic stimulation(28.4％).CONCLUSION:Transcranial magnetic stimulations can improve the depressive symptoms of patients with treatment-resistant depression.Among them,the high-frequency repetitive transcranial magnetic stimulation mode has the best effect on improving the depressive symptoms of patients with treatment-resistant depression,followed by the intermittent θ burst stimulation mode.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Mitochondrial diabetes mellitus(MDM)is a type of diabetes caused by mitochondrial gene mutations resulting in progressive secretory function defects of pancreatic islet β cells.MDM is a rare single-gene genetic disease,accounting for about 1%of all diabetes mellitus.We reported a case of MDM patient and their family.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.