ObjectiveTo understand the incidence and death of female breast cancer patients and the premature death caused by breast cancer in Putuo District of Shanghai， and to reduce the incidence of breast cancer， mortality and the probability of early death， and to provide reference for realizing the control target of the probability of early death of major chronic diseases. MethodsThe incidence and death data of the registered female residents with breast cancer in Putuo District of Shanghai from 2004 to 2019 were collected using Shanghai Population-based tumor registration management system. The crude incidence rate， standardized incidence rate， crude mortality rate， standardized mortality rate， age-specific incidence rate， age-specific mortality rate and other indicators were calculated. The Joinpoint regression model was used to calculate the annual percentage change （APC） and average annual percentage change （AAPC） of breast cancer incidence， mortality and premature death probability， and to analyze the changing trend. ResultsFrom 2004 to 2019， the crude incidence of breast cancer in Putuo District of Shanghai increased from 75.76/10⁵ to 95.77/10⁵ （APC=2.26%， t=6.05， P<0.01）， while the standardized incidence did not decrease significantly during 2004‒2008 （APC=-4.83%， t=-1.81， P=0.10） and showed an upward trend after 2008 （APC=1.67%， t=2.84， P=0.02）. The crude mortality rate changed from 18.52 per 10⁵ to 21.63 per 10⁵ （APC= 1.51%， t=1.52， P=0.15）， and the standardized mortality rate decreased from 9.91/10⁵ to 7.44/10⁵ （APC=-1.46%， t=-2.43， P=0.03）. The incidence rate in the group of 30‒69 years increased from 98.39/10⁵ to 111.75/10⁵ （APC=1.14%， t=3.05， P=0.01）， and the mortality rate increased from 16.13/10⁵ to 19.30/10⁵ （APC=0.48%， t=0.84， P=0.41）. The incidence rate of patients aged ≥70 years varied from 165.68/10⁵ to 139.53/10⁵ （APC=1.54%， t=1.25， P=0.23）， and the mortality rate changed from 85.08/10⁵ to 56.64/10⁵ （APC=-0.18%， t=-0.08， P=0.94）. The probability of premature death from breast cancer decreased from 7.73‰ to 6.61‰ （APC=-1.56%， t=-2.30， P=0.04）. ConclusionThe risk of female breast cancer morbidity and death can not be ignored， and the control pressure of premature death probability is still large. Attention should be paid to the age group of 30‒69 years old， and further measures should be taken to control the increase of incidence and to reduce mortality， so as to reduce the probability of premature death of female breast cancer， and promote the realization of the overall control goal of premature death probability.

Objective To identify lipid metabolism genes in cerebral infarction;To explore the intervention effect of Huoxue Rongluo Prescription.Methods Multi-chip combined differential analysis(GSE61616,GSE30655)was used to identify lipid metabolism genes in cerebral infarction in combination with Reactome database,and the expression differences of lipid metabolism genes in cerebral infarction were identified and verified in GSE97537 chip;Pearson correlation analysis was used to analyze the correlation of 51 cerebral infarction samples in GSE61616,GSE30655,GSE97537,GSE137595,GSE22255,GSE163614,and GSE78731 datasets;PPI,GO and KEGG analysis of lipid metabolism genes in cerebral infarction were performed through STRING database and R clusterProfiler package.SD rats were made to the model of cerebral infarction,and was administered with Huoxue Rongluo Prescription extract 11.7 g/kg by intragastric administration for 7 days.The symptoms of neurological deficit,the changes of Nissl bodies and the mRNA expressions of PLA2G4A,SPHK1,and PTGES key genes in lipid metabolism in cerebral infarction were observed.Results TSPO,CYP1B1,PLIN2,CH25H,PLA2G4A,ANGPTL4,PTGS1,SPHK1,and PTGES were identified as lipid metabolism genes in cerebral infarction,and were significantly highly expressed and positively correlated in cerebral infarction.Among them,PTGS1,PLA2G4A,and SPHK1 interacted with each other,which were the key genes of lipid metabolism in cerebral infarction;the lipid metabolism gene in cerebral infarction mainly exerted molecular functions such as oxidoreductase activity,iron ion binding,heme binding,etc.,mediating arachidonic acid metabolism,phospholipase D signaling pathway,VEGF signaling pathway,involved in regulation of lipid metabolism process,fatty acid metabolism process,fatty acid derivative metabolism process.The symptoms of neurological deficit in the model rats with cerebral infarction were severe(P<0.001),and Huoxue Rongluo Prescription could effectively improve the neurological deficit of model rats(P<0.001).The Nissl staining indicated that the neuronal structure was abnormal and the number was significantly reduced after cerebral infarction(P<0.001).Huoxue Rongluo Prescription could increase the number of neurons(P<0.001)and repair the neuronal structure.RT-qPCR showed that the key genes of lipid metabolism in cerebral infarction were significantly higher in cerebral infarction(P<0.001),corroborated with the bioinformatics results,and Huoxue Rongluo Prescription could reduce the expression of key lipid metabolism genes of PTGS1,PLA2G4A,and SPHK1(P<0.001,P<0.01,P<0.05).Conclusion Huoxue Rongluo Prescription can down-regulate the expressions of PTGS1,PLA2G4A,SPHK1,exert molecular functions such as oxidoreductase activity,iron ion binding,heme binding,and mediate arachidonic acid metabolism,phospholipase D signaling pathway,and VEGF signaling pathway.It participates in the process of lipid metabolism regulation,fatty acid metabolism,and fatty acid derivative metabolism,increases the number of Nissl bodies,improves the symptoms of neurological deficits,and exerts neuroprotective effects.

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Objective:To evaluate the clinical value of Xing's ureteroileal anastomosis technique in radical cystectomy.Methods:The data of 38 patients who underwent radical cystectomy with Xing's ureteroileal anastomosis technique at Cancer Hospital, Chinese Academy of Medical Sciences and Beijing Chaoyang Hospital from July 2013 to June 2021 were retrospectively reviewed. There were 30 males and 8 females. The mean age was 61.6±15.1 years old. The mean body mass index (BMI) was 25.1±2.7 kg/m 2. The American Society of Anesthesiology (ASA) graded 25 cases as grade 1, 10 cases as grade 2 and 3 cases as grade 3. There were 35 cases with stage cT 2N 0M 0 and 3 cases with cT 3N 0M 0. All patients underwent radical cystectomy and ileal conduit, and the ureteroileal anastomosis was performed using the Xing's ureteroileal anastomosis technique. Afferent loop entry was divided equally into two lumens. After 1.5 cm-long lengthwise incisions, each ureter was directly and end-to-end anastomosed to the aforementioned lumens. Postoperative information was recorded, including ureteric stricture, ureteric reflux, hydronephrosis, anastomotic leakage, renal calculus, urinary tract infection, and pyelonephritis. Results:Ureteroileal anastomosis was performed successfully in 38 cases with 76 units. The median follow-up time was 35.6 (17.0, 46.3) months. Three patients developed unilateral anastomotic stenosis after operation. Five patients had unilateral ureteral reflux. Two patients had unilateral hydronephrosis. No anastomotic leakage, urinary tract infection, or pyelonephritis occurred after the operation. Renal calculus appeared in 3 cases, all on the left unit.Conclusions:Xing's ureteroileal anastomosis technique is a simple method with few postoperative and good functional outcomes.

Humans ; Hospital Mortality ; Pulmonary Embolism ; Comorbidity ; Registries ; Neoplasms/complications*

ObjectiveTo understand the premature mortality of the most common cancers in the residents in Putuo District， Shanghai for the goal to decrease the probability of premature cancer mortality. MethodsLife table was used to calculate crude and age-standardized incidence rate， mortality， and the probability of premature mortality caused by cancers among Putuo residents from 2004 to 2016. The annual percent change was used to describe the change of these indexes. ResultsFrom 2004 to 2016， the crude incidence rate increased from 383.51/10⁵ to 573.94/10⁵ （APC=3.52%， P<0.01） while the age-standardized incidence rate changed from 223.20/10⁵ to 241.38/10⁵ （APC=3.52%， P<0.01）. The crude mortality rate changed from 229.99/10⁵ to 269.94/10⁵ （APC=1.64%， P<0.01） while the age-standardized mortality rate changed from 122.48/10⁵ to 87.49/10⁵ （APC=-2.04%， P<0.01）. The probability of premature mortality changed form 7.14% to 5.53% （AAPC=-2.29%， P<0.01）. The probability of premature mortality for male changed from 8.73% to 7.10% （AAPC=-1.74%， P=0.01） while the female from 5.54% to 3.88% （AAPC=-2.88%， P=0.08）. Trachea， bronchus and lung cancers were the top cancers causing premature mortality both for male and female. The probability of premature mortality showed a downward trend for both male liver cancer （APC=-3.83%， P=0.01） and female stomach cancer （APC=-4.17%， P<0.01）. The other types cancers did not show the significant changes （P>0.05）. Male nasopharyngeal carcinoma and female cervical carcinoma ranked top ten cancers causing probability of premature mortality but not the top ten cancers according to the crude mortality rate. ConclusionThe premature death caused by cancers shows a downward trend in general， but not in the female and most common cancers. The burden to reduce the premature mortality is still heavy. More efforts should focus on those cancers that are preventable and detectable by screening in order to decrease the premature cancer mortality.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient's appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
Bone Regeneration ; Bone Transplantation/methods* ; Hedgehog Proteins ; Humans ; Mandible/surgery* ; Osteogenesis

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, and Th17 cells are key factors in the pathogenesis of human inflammatory conditions, such as RA. Catalpol (CAT), a component in Rehmanniae Radix (RR), has been found to regulate human immunity. However, the effects of CAT on Th17 cell differentiation and improvement of RA are not clear. Materials and Methods: Collagen-induced arthritis (CIA) mice were constructed to detect the effects of CAT on arthritis and Th17 cells. The effect of CAT on Th17 differentiation was evaluated with let-7g-5p transfection experiments. Flow cytometry was used to detect the proportion of Th17 cells after CAT treatment. Levels of interleukin-17 and RORγt were assessed by qRT-PCR and enzyme-linked immunosorbent assay. The expression of signal transducer and activator of transcription 3 (STAT3) was determined by qRT-PCR and Western blot. Results: We found that the proportion of Th17 cells was negatively associated with let-7g-5p expression in CIA mice. In in vitro experiments, CAT suppressed traditional differentiation of Th17 cells. Simultaneously, CAT significantly decreased Tregs-to-Th17 cells transdifferentiation. Our results demonstrated that CAT inhibited Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p and that the suppressive effect of CAT on traditional differentiation of Th17 cells is not related with let-7-5p. Conclusion Our data indicate that CAT may be a potential modulator of Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p to reduce the expression of STAT3. These results provide new directions for research into RA treatment.

Objective:To investigate the clinical effect and demonstrate the techniques of single position laparoscopic nephroureterectomy.Methods:The clinical data of 84 upper urinary tract urothelial carcinoma patients admitted to the Cancer Hospital Chinese Academy of Medical Sciences from September 2018 to July 2022 were retrospectively analyzed, including 39 males and 45 females, with a median age of (64.9±9.3)years and mean BMI of(24.7±3.4)kg/m 2. The tumor was located on the left side in 47 cases and the right side in 37 cases. All 84 patients received single position laparoscopic nephroureterectomy. According to different treatment methods, they were divided into two groups, including 67 cases undergoing nephrectomy first, and then bladder cuff excision was performed along ureter(traditional group), 17 cases undergoing bladder cuff excision before clamping the ureter below the tumor, and then nephrectomy was performed along the ureter to the head side (modified group). There was no statistically significant in the comparison of age [(65.5±9.4)years vs.(62.7±8.9)years], BMI[(24.9±3.5)kg/m 2vs.(23.9±3.3)kg/m 2], left/right side tumor of(38/29 cases vs. 9/8 cases), tumor location (in renal pelvis or calyx or upper/middle/lower ureter being 46/9/12 cases vs. 13/2/2 cases)and tumor stage(T 1-2/T 3-4: 54/13 cases vs. 15/2 cases) between traditional group and modified group ( P>0.05). The operation time, estimate blood loss, postoperative intestinal function recovery time and postoperative drainage time were recorded and compared. Results:All 84 cases were successfully completed without conversion to open surgery. The mean operation time was (160.4±50.1)min, the mean estimated blood loss was(59.4±24.4)ml, the median postoperative intestinal function recovery time was 1(1, 2)d and the mean postoperative drainage time was (4.8±1.9)d(No drainage tube was placed in 4 patients). No Clavien Dindo >grade 3 complications occured. There was no significant difference in the comparison of operation time [(159.2±52.9)min vs. (164.7±38.1)min], estimate blood loss [(60.5±26.2)ml vs. (55.0±17.5)ml], postoperative intestinal function recovery time [1(1-2)d vs. 2(1-2)d] and drainage removal time [(4.8±1.8)d vs. (5.2±2.0)d] between traditional group and modified group ( P>0.05). The postoperative pathology of 84 cases was urothelial carcinoma, and the pathological results of the resection margin were negative. The median follow-up of 84 upper tract urothelial carcinoma patients was 13(3, 28)months. Five patients were lost to follow-up. In traditional group, 5 patients had bladder tumor recurrence, and 5 patients had distant metastasis. In modified group, no bladder tumor recurrence occurred and 1 patient had distant metastasis. Conclusions:Laparoscopic nephroureterectomy in single position is a safe and effective minimally invasive technique for the treatment of upper urinary tract urothelial carcinoma. Treatment of the bladder cuff excision firstly is more in line with the principle of tumor-free and increase surgical space.

Objective:To evaluate the value of 68Ga-labeled prostate-specific membrane antigen( 68Ga-PSMA PET/CT)in the diagnosis of prostate cancer(PCa) and determination of the strategy on neurovascular bundle(NVB)preservation and lymphadenectomy before surgery. Methods:We retrospectively analyzed the clinical data of 46 patients with newly diagnosed PCa who underwent 68Ga-PSMA PET/CT from June 2018 to October 2019. The median age was 66.50 (60.00, 69.25) years old and the median PSA was 15.97(8.58, 33.10)ng/ml. Forty-one patients were diagnosed PCa and 5 were diagnosed with benign prostatic hyperplasia or prostatitis by 68Ga-PSMA PET/CT, 6 were diagnosed with lymph nodes metastasis. Forty patients underwent mpMRI, 33 were diagnosed PCa, and 6 were diagnosed with lymph nodes metastasis. Seventeen patients underwent 11C-choline PET/CT, 12 were diagnosed PCa, and 4 were diagnosed with lymph nodes metastasis. Among the 41 patients which were diagnosed PCa by 68Ga-PSMA PET/CT, 26 were confirmed with PCa by needling biopsy, 12 did not undergo the needling biopsy and 3 had negative biopsy; 22 were in the high-risk group, and 19 were in the low- and medium-risk group. All 41 patients underwent radical prostatectomy. The strategy of NVB preservation was determined by the position of the PCa reported by 68Ga-PSMA PET/CT. If the tumor was close to the unilateral prostate capsule, the healthy part of the NVB would be preserved. And if the tumor was limited in the prostate gland, bilateral NVB would be preserved. The NVB was preserved in 16 cases(6 cases unilateral and 10 cases bilateral). In addition to routine lymph node dissection for patients in the high-risk group, lymph node dissection was also performed on patients with 68Ga-PSMA PET/CT that showed positive lymph nodes in the low- and medium-risk groups. The paired chi-square or Fisher exact test was used to compare the sensitivity and specificity of 68Ga-PSMA PET/CT, mpMRI, and 11C-choline PET/CT for lesion detection. Spearman analysis was used to examine the correlation between the SUV max, Gleason score, and the PSA value before treatment. Results:Forty-one patients undergoing radical resection were diagnosed PCa by postoperative pathology, and no cancer tissue was observed at the surgical margin; the median Gleason score was 8(7, 9); 20 cases (48.8%) had a pathological stage ≤pT 2c; 21 cases (51.2%)≥pT 3; 7 cases were N+ (11 positive lymph nodes). Seven cases (17.1%) had complications of Clavien-Dindo ≤ grade 2 within 30 days after surgery, and there was no complication above grade 3 after surgery. The median follow-up time of the 41 patients was 16(12, 20). The rate of urinary control was 46.3%, 95.1%, and 100% after 1 month, 6 months, and 12 months follow-up respectively. Among the five patients that did not undergo surgery, the PSA value of 4 decreased after antibiotic treatment, and biopsy was performed in 1 case without PSA decreasing, and no carcinoma was found. The sensitivity of 68Ga-PSMA PET/CT on the primary PCa was 100%(41/41), which was significantly better than that of 11C-choline(80%, 12/15, P=0.016)and mpMRI (83.7%, 31/37, P=0.009), while no statistical significance was observed between the specificity of 68Ga-PSMA PET/CT (5/5)and 11C-choline PET/CT(2/2, P=1.000), 68Ga-PSMA PET/CT and mpMRI(1/3, P=0.107). Of the 41 patients that were diagnosed with PCa, the sensitivity of 68Ga-PSMA PET/CT to lymph nodes metastases(71.4%, 5/7) had a significant difference with that of mpMRI(16.7, 1/6, P=0.016), but no statistical difference with 11C-choline (75%, 3/4, P=1.000). Analysis of the relationship between SUV max of 68Ga-PSMA PET/CT, Gleason score, and PSA value before treatment revealed that the SUV max of 68Ga-PSMA PET/CT in patients with Gleason score ≥8 and <8 score were 19.60(9.58, 24.38) and 8.55 (5.18, 12.88); SUV max of patients with PSA values ≥20 ng/ml and <20 ng/ml before treatment were 19.40 (13.00, 23.50) and 8.40 (5.35, 13.95), respectively, the differences were statistically significant (all P<0.05). Conclusions:68Ga-PSMA PET/CT had high sensitivity and specificity for the diagnosis of primary prostate cancer lesions, but the sensitivity for the diagnosis of lymph node metastasis was not enough to guide the preoperative decision of whether to remove the lymph node and the scope of the removal. However, the treatment strategy of whether to retain NVB could be formulated according to the tumor location displayed by 68Ga-PSMA PET/CT before surgery.