Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Objective:To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins.Methods:A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ2 tests, and linear regression analysis. Results:One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M(IQR),3.0(4.3) vs.4.0(5.8), Z=-2.038, P=0.040).Additionally, the chronic venous insufficiency patients′ quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs.82.5(17.0), Z=-2.627, P=0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs.12.0(7.0) weeks, Z=-3.217, P<0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ2=0.453, P=0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ2=4.800, P=0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions:CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

Objective:To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins.Methods:A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ2 tests, and linear regression analysis. Results:One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M(IQR),3.0(4.3) vs.4.0(5.8), Z=-2.038, P=0.040).Additionally, the chronic venous insufficiency patients′ quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs.82.5(17.0), Z=-2.627, P=0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs.12.0(7.0) weeks, Z=-3.217, P<0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ2=0.453, P=0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ2=4.800, P=0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions:CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

Objective: To investigate the mortality of malignant tumors, diabetes, cardio-cerebrovascular diseases and chronic respiratory diseases and trends in probability of premature mortality due to these four chronic diseases in Jiangmen City, Guangdong Province from 2012 to 2021, so as to provide the evidence for perfecting the chronic disease control strategy. Methods: The mortality of malignant tumors, diabetes, cardio-cerebrovascular diseases and chronic respiratory diseases among household registered residents in Jiangmen City from 2012 to 2021 were collected from the Guangdong Provincial Population Death Information Registration Management System, and the crude mortality, standardized mortality by the population of the Fifth National Population Census in China in 2000 and probability of premature mortality were calculated. The trends in mortality and probability of premature mortality were analyzed using average annual percent change (AAPC), and whether achieving the targets for the probability of premature mortality due to four chronic diseases in 2025 and 2030 were evaluated. Results: A total of 226 012 deaths occurred due to four chronic diseases in Jiangmen City from 2012 to 2021, and the overall crude mortality and standardized mortality rates were 569.22/105 and 283.29/105, with a reduction in the probability of premature mortality from 15.04% to 12.05% (AAPC=-2.403%, Z=-7.603, P<0.001). The probability of premature mortality due to four chronic diseases decreased from 19.21% to 16.38% in males, and from 10.42% to 7.58% in females (AAPC=-1.893% and -3.085%, Z=-5.262 and -9.811, both P<0.001). The probability of premature mortality due to diabetes appeared a tendency towards a rise (AAPC=2.317%, Z=2.548, P=0.034), and the probability of premature mortality due to cardio-cerebrovascular diseases showed a tendency towards a decline (AAPC=-4.826%, Z=-13.590, P<0.001), while no significant changing trend was seen in the probability of premature mortality due to malignant tumors or chronic respiratory diseases (AAPC=-0.751% and -2.461%, Z=-1.532 and -1.730, P=0.125 and 0.122). The predicted probability of premature mortality due to four chronic diseases was 10.92% in 2025 and 9.66% in 2030 in Jiangmen City, which were both lower than the target (11.21% and 9.81%). Conclusions The probability of premature mortality due to four chronic diseases appeared a tendency towards a decline in Jiangmen City from 2012 to 2021, which can reach the target in 2025 and 2030. Males should be given a high priority for interventions of chronic diseases, and diabetes control should be reinforced.

OBJECTIVE: To investigate the effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 160 patients with ACL injuries who met the selection criteria and were admitted between November 2020 and August 2021 were selected and divided into 4 groups according to the random number table method (n=40). Group A began to take imrecoxib 3 days before operation (100 mg/time, 2 times/day); group B began to take imrecoxib 1 day before operation (100 mg/time, 2 times/day); group C took 200 mg of imrecoxib 2 hours before operation (5 mL of water); and group D did not take any analgesic drugs before operation. There was no significant difference in gender, age, body mass index, constituent ratio of meniscal injuries with preoperative MRI grade 3, constituent ratio of cartilage injury Outerbridge grade 3, and visual analogue scale (VAS) score at the time of injury and at rest among 4 groups (P>0.05). The operation time, hospitalization stay, constituent ratio of perioperative American Society of Anesthesiologists (ASA) grade 1, postoperative opioid dosage, and complications were recorded. The VAS scores were used to evaluate the degree of knee joint pain, including resting VAS scores before operation and at 6, 24, 48 hours, and 1, 3, 6, and 12 months after operation, and walking, knee flexion, and night VAS scores at 1, 3, 6, and 12 months after operation. The knee injury and osteoarthritis score (KOOS) was used to evaluate postoperative quality of life and knee-related symptoms of patients, mainly including pain, symptoms, daily activities, sports and entertainment functions, knee-related quality of life (QOL); and the Lysholm score was used to evaluate knee joint function. RESULTS: All patients were followed up 1 year. There was no significant difference in operation time, hospitalization time, or constituent ratio of perioperative ASA grade 1 among 4 groups (P>0.05); the dosage of opioids in groups A-C was significantly less than that in group D (P<0.05). Except for 1 case of postoperative fever in group B, no complications such as joint infection, deep vein thrombosis of the lower extremities, or knee joint instability occurred in each group. The resting VAS scores of groups A-C at 6 and 24 hours after operation were lower than those of group D, and the score of group A at 6 hours after operation was lower than those of group C, and the differences were significant (P<0.05). At 1 month after operation, the knee flexion VAS scores of groups A-C were lower than those of group D, the walking VAS scores of groups A and B were lower than those of groups C and D, the differences were significant (P<0.05). At 1 month after operation, the KOOS pain scores in groups A-C were higher than those in group D, there was significant difference between groups A, B and group D (P<0.05); the KOOS QOL scores in groups A-C were higher than that in group D, all showing significant differences (P<0.05), but there was no significant difference between groups A-C (P>0.05). There was no significant difference in VAS scores and KOOS scores between the groups at other time points (P>0.05). And there was no significant difference in Lysholm scores between the groups at 1, 3, 6, and 12 months after operation (P>0.05). CONCLUSION Compared with the traditional analgesic scheme, applying the concept of preemptive analgesia with imrecoxib to manage the perioperative pain of ACL reconstruction can effectively reduce the early postoperative pain, reduce the dosage of opioids, and promote the early recovery of limb function.
Humans ; Quality of Life ; Analgesics, Opioid ; Analgesia ; Osteoarthritis, Knee ; Pain, Postoperative/prevention & control* ; Anterior Cruciate Ligament Reconstruction ; Knee Injuries

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Objective:To investigate the application value of self-pulling and latter transection (SPLT) technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 103 patients with Siewert type Ⅱ adenocarcinoma of esophagogastric junction in clinical stage Ⅰ-Ⅱ who were admitted to Shanxi Cancer Hospital from January 2018 to January 2020 were collected. There were 65 males and 38 females, aged from 45 to 79 years, with a median age of 59 years. Of 103 patients, 49 cases undergoing totally laparoscopic proximal gastrectomy with double-tract reconstruction of SPLT were assigned into the SPLT group, 54 cases undergoing totally laparoscopic proximal gastrectomy with conventional double-tract reconstruction were assigned into the traditional group. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone inter-view to detect postoperative reflux esophagitis of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and the Wilcoxon test was used for comparison between groups. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Intraoperative situations: the operation time, digestive tract reconstruction time, volume of intraoperative blood loss, the number of inferior mediastinal lymph nodes dissected, cases with auxiliary incisions for the SPLT group were (261±48)minutes, (26±4)minutes, (114±42)mL, 8.0(6.5,9.5), 1, respectively. The above indicators were (244±42)minutes, (30±6)minutes, (118±46)mL, 5.5(4.0,8.0), 9 for the traditional group, respectively. There were significant differences in the digestive tract reconstruction time, the number of inferior mediastinal lymph nodes dissected and cases with auxiliary incisions between the two groups ( t=-3.34, Z=-4.05, χ2=4.72, P<0.05). There was no significant difference in the operation time or volume of intraoperative blood loss between the two groups ( t=1.87, -0.47, P>0.05). (2) Postoperative situations: duration of postopera-tive hospital stay and cases with postoperative complications were (11.5±2.7)days and 4 for the SPLT group, versus (12.5±4.3)days and 9 for the traditional group, showing no significant difference between the two groups ( t=-1.47, χ2=1.68, P>0.05). There were 13 of 103 patients with postopera-tive complications, including 5 cases of left pleural effusion, 4 cases of anastomotic leakage, 2 cases of mild pneumonia, 1 case of incision infection, 1 case of chylous leakage. Four patients had anasto-motic leakage at the esophagojejunostomy, the abdominal esophagus of whom was invaded by more than 1 cm. During the operation, mediastinal drainage tubes were placed through the abdominal wall. The 4 patients were cured after enteral and parenteral nutrition support and adequate drainage, and the remaining patients with complications were cured after symptomatic treatment. (3) Follow-up: of 49 patients in the SPLT group, 43 cases were followed up for (18±4)months. During the follow-up, 1 case showed reflux esophagitis by gastroscopy, with the incidence of 2.33%(1/43). Of 54 patients in the traditional group, 53 cases were followed up for (17±4)months. During the follow-up, 4 cases showed reflux esophagitis by gastroscopy, with the incidence of 7.55%(4/53). There was no significant difference in the incidence of reflux esophagitis between the two groups ( χ2=0.47, P>0.05). Conclusions:SPLT technology is feasible for double anti-reflux double-tract reconstruction of proximal gastrectomy. Compared with traditional double-tract reconstruction of totally laparos-copic proximal gastrectomy, SPLT technology can reduce the auxiliary incisions, increase the number of lower mediastinal lymph nodes dissected, and shorten the digestive tract reconstruction time.

There are still many controversies in the surgical treatment of esophagogastric junction tumors in terms of surgical approach, cleaning range, and resection scope. The reason is the confusion about the scope of the esophagogastric junction. The previous domestic and foreign anatomy descriptions of this part are not enough to solve the current problems. Based on a large number of basic anatomy and clinical operations, this article proposes that the esophagogastric junction may be wrapped by a complete and separate esophagogastric junction membrane with independent anatomy other than infracardiac bursa. The structure of the transitional tissue, mainly from the distribution of submucosal veins, explained the relationship and significance of tissue transitional changes and clinical operations, and made a reasonable analysis of the current controversy based on the anatomical characteristics, which is worthy of further investigation.