INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

ObjectiveTo further study the pathogenic role of different types of Chlamydia trachomatis （CT） proteins in tubal factor infertility， evaluate the clinical detection value of Chlamydia trachomatis protein antibody in predicting tubal factor infertility. MethodsA total of 58 cases of tubal factor infertility （TFI）， 41 cases of fertile controls （FC） and 18 cases of infertile controls （IFC） were included. For serum detection， first， CT-IgG ELISA kit was used to detect the expression of CT-IgG in serum of three groups of people； then， 6 kinds of Chlamydia trachomatis proteins were expressed and purified in the early stage to establish the antibody test for these proteins， and ELISA detection method was used to detect the expression of their antibodies in the serum of TFI group， FC group and IFC group， respectively； and finally， the antibody OD value of the 6 kinds of Chlamydia trachomatis proteins in the three groups of subjects were statistically described， and CT-IgG was used as the reference standard to draw the receiver operating characteristic curve （ROC curve） of each CT antibody. The Youden Index determines the cutoff value for each antibody. Taking TFI as the reference class， two disordered multiple classification logistic regression models were established with the FC and IFC groups， respectively； and the reference class was used to explore the value of various antibodies and age in predicting TFI， FC and IFC of Chlamydia trachomatis. The back-off method was used to screen the variables. ResultsThe OD value of CT376 antibody in the TFI group was higher than that in the FC group （0.86 vs. 0.60， P=0.026）. The CT376 antibody OD value in the TFI group was higher than that in the IFC group （0.86 vs. 0.64， P=0.026）. The CT443 antibody OD value in the IFC group was higher than that in the TFI group （0.59 vs. 0.34， P=0.036） and higher than that in the FC group （0.59 vs. 0.30， P=0.02）. The multiple classification logistic regression analysis established between TFI and FC showed that CT-IgG ［P<0.001， OR=0.084， 95%CI （0.025， 0.284）］， CT376 antibody ［P=0.068， OR=0.359， 95%CI （0.120， 1.078）］. CT-IgG is an independent risk factor for tubal infertility， and CT376 antibody cannot be an independent risk factor for tubal infertility. The multiple classification logistic regression analysis established between TFI and IFC showed that among infertile patients， CT-IgG ［P<0.05， OR=0.194， 95%CI （0.046， 0.817）］， CT376 antibody ［P<0.05， OR=0.176， 95%CI （0.038， 0.818）］ and CT381 antibody ［P<0.05， OR=0.112， 95%CI （ 0.016， 0.796）］ were independent risk factors for tubal infertility. ConclusionThe expression of CT376 antibody in tubal infertility patients is higher than that in fertile and infertile controls， suggesting that CT-induced tubal factor infertility may be related to CT376. CT-IgG， and CT376 antibodies are meaningful in predicting CT-induced tubal factor infertility.

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T₂ fracture, 1 case of T₃ fracture, 3 cases of T₄ fracture, 3 cases of T₅ fracture, and 7 cases of T₆ fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T₁ fracture, 5 cases of T₄ fracture, 2 cases of T₅ fracture and 9 cases of T₆ fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.
Female ; Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Robotics ; Blood Loss, Surgical ; Bone Cements ; Retrospective Studies ; Thoracic Vertebrae/surgery*

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.
Male ; Humans ; Female ; Adult ; Middle Aged ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Aged ; Carcinoma, Renal Cell/epidemiology* ; Incidence ; Databases, Factual ; China ; Kidney Neoplasms/epidemiology* ; Global Health

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ² test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ²: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ²=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ²=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.
Adenocarcinoma/surgery* ; Aged ; Esophageal Neoplasms ; Esophagogastric Junction/surgery* ; Female ; Humans ; Lymph Node Excision/methods* ; Lymphatic Metastasis/pathology* ; Male ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Survival Analysis

Objective: To evaluate the postoperative quality of life in patients after totally laparoscopic total gastrectomy (TLTG). Methods: A retrospective cohort study based on propensity score matching was performed. Clinical and follow-up data of patients who underwent laparoscopic radical gastrectomy at Union Hospital of Fujian Medical University from January 2014 to May 2015 were collected. Case indusion criteria: (1) primary gastric cancer confirmed by postoperative pathology; (2) receiving TLTG or laparoscopic-assisted total gastrectomy (LATG);(3) R0 resection; (4) completing follow-up for 12 months and complete follow-up data. Exclusion criteria: (1) gastric stump cancer; (2) concurrent tumor; (3) distal metastasis found during operation; (4) history of upper abdominal operation. According to surgical procedures, patients were divided into the LATG group (1076 cases) and the TLTG group (106 cases). To eliminate potential bias in baseline data between the two groups, the propensity score was calculated using a logistic regression model with the following covariates, including age, sex, body mass index, American Society of Anesthesiologists score, tumor location, tumor size, pathology type, and stage. The two groups were matched using a 1:2 propensity assessment ratio and a caliper width of 0.01 standard deviation was specified. The primary outcomes were the quality of life of the two groups at 3, 6 and 12 months after gastrectomy, including physical symptoms and social function. Higher function score indicated better function, and higher symptom score presented worse symptoms. Quality of life score = (100 - somatic symptom scale score + social function scale score) / 2. The secondary outcomes were postoperative nutritional recovery and food tolerance at 3, 6 and 12 months after gastrectomy. The categorical variables were expressed as n(%), and compared using the χ² test or Fisher exact test. The continuous variables conforming to the normal distribution were represented by Mean ± SD and compared with the paired t-test. Repeated measurement of variance was used to compare nutrition-related indicators within the group among pre-operation, postoperative 1, 3, 6, 12 months. Results: After PSM, there were no significant differences in clinicopathological baseline data between the TLTG group (n=104) and the LATG group (n=208) (all P>0.05). The physical symptoms scores in the TLTG group before operation and 3, 6 and 12 months after operation were 8.6±5.8, 15.5±8.4, 10.1±5.9 and 6.1±2.4 respectively (F=43.493, P<0.001). In the LATG group, the above mentioned scores were 9.7±6.9, 23.7±10.4, 13.3±8.3 and 8.5±4.2 respectively (F=112.588, P<0.001). Compared with the LATG group, the symptom scores in the TLTG group were lower at 3 and 6 months after operation, and the differences were statistically significant (t=-3.653, P<0.001; t=-2.513, P=0.012). At 12 months after operation, although the physical symptom score in the TLTG group was also lower than that in LATG group, the difference was not statistically significant (t=-1.487, P=0.138). The social function scores in the TLTG group before operation and 3, 6 and 12 months after operation were 90.3±8.9, 77.5±14.3, 87.4±10.3 and 91.7±6.7 respectively (F=28.524, P<0.001). In the LATG group, the above mentioned scores were 92.5±6.3, 68.5±16.8, 79.8±14.7 and 84.7±11.1 respectively (F=57.975, P<0.001). Compared with the LATG group, the social function scores of patients in the LATG group were higher at 3, 6 and 12 months after operation (t=3.543, P<0.001; t=3.216, P=0.001; t=2.235, P=0.026). The total scores of quality of life at 3, 6 and 12 months after operation in the TLTG group were 81.0±15.6, 88.3±8.1 and 93.3±9.1 respectively, and the above mentioned scores in the LATG group were 72.4±13.6, 83.3±11.5 and 88.1±7.7 respectively, whose differences at corresponding time point were all significant between the two groups (all P<0.05). The change of total body mass[(-8.4±1.4)% vs. (-13.2±1.6)%, t=2.273, P=0.024], serum albumin[(-5.1±0.7)% vs. (-7.4±0.8)%,t=2.095, P=0.037], meal quantity [(-15.6±4.7)% vs. (-24.1±6.0)%, t=2.885, P=0.004] and meal times [(20.8±7.1)% vs. (30.6±11.5)%, t=3.043, P<0.001] in the TLTG group were significantly lower than those in the LATG group one year after operation (all P<0.05). At 3, 6 and 12 months after operation, the diet proportions of solid and soft food in the TLTG group were higher than those in the LATG group (all P<0.05). Conclusions: Compared with LATG, patients with gastric cancer undergoing TLTG have better health-related quality of life and faster recovery of nutrition.
Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Postoperative Complications/surgery* ; Propensity Score ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

Objective:To analyze bladder cancer mortality in China from 2004 to 2018. Methods:The dataset of bladder cancer mortality from 2004 to 2018， based on 605 national surveillance sites and regularly published by the Chinese Center for Disease Control and Prevention， was collected and age-standardized according to the demographic structure of China in 2000. The crude mortality rate （CMR）， the age-standard mortality rate （ASMR）， and the ratio of ASMRs of rural to urban areas（RR）were calculated to analyze the distributions of the mortality of bladder cancer stratified by age， sex， region （rural/urban areas， eastern/central/western areas） or time. Results:The CMR of bladder cancer in China from 2004 to 2018 was 1.69/10⁵， and the ASMR was 1.09/10⁵. The temporal trend on the CMR of bladder cancer from 2004 to 2018 increased significantly （APC=2.91%，P<0.001）， whereas the trend on the ASMR decreased a little （APC=-1.29，P=0.008）. The temporal trend on the CMR of bladder cancer in the males increased （APC=3.29%，P<0.001）， whereas the trend on the ASMR did not change. The temporal trend on the CMR of bladder cancer in the female increased （APC=2.12%，P<0.001）， whereas the trend on the ASMR decreased （APC=-1.94，P=0.008）. Both the CMR and ASMR of urban areas were higher than those of rural areas （P<0.05）. However， the temporal trend on the ASMR of bladder cancer in the urban decreased significantly （APC=-2.05%，P=0.002）， mainly exhibited in eastern and western urban. The ASMR of eastern urban areas was higher than that of western urban areas. The temporal trend on the ASMR of bladder cancer in the rural did not change （P>0.05）， and no differences in the ASMR were detected between eastern， central and western rural areas. The gaps between rural and urban areas in the eastern （P<0.001） or western （P=0.002） region reduced. Although the temporal trend on the ASMR in urban people over 40 years old decreased significantly， the ASMR of urban people over 60 years old was much higher than that of other age groups in the urban or any age groups in rural areas. Conclusion:The age group over 60 years old in the urban is the major target population for bladder cancer prevention and treatment. Screening， diagnosis and treatment for bladder cancer in rural should be strengthened.