Objective:To explore and verify the value of neoadjuvant rectal (NAR) score in predicting the prognosis of patients with middle and low locally advanced rectal cancer.Methods:A retrospective analysis of 207 patients with middle and low locally advanced rectal adenocarcinoma who received neoadjuvant radiotherapy and chemotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2015 to December 2021 was performed. The neoadjuvant radiotherapy regimen was pelvic external irradiation of 45-50.4 Gy, 1.8 Gy/f, 5 times per week and concurrent oral capecitabine chemotherapy on days 1-14 and 22-36 during radiotherapy. Total mesorectal excision (TME) was then performed. The NAR score was calculated based on the initial clinical stage and postoperative pathological stage, and divided into the low (<8), medium (8-16) and high (>16) layers, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences in DFS and OS among different NAR score layers were compared using the log-rank test. Some patients received consolidation chemotherapy during the interval between concurrent radiotherapy-chemotherapy and surgery, even the total neoadjuvant therapy (TNT) model. Subgroup analysis was further used to verify the predictive value of the NAR score in the strengthened neoadjuvant therapy model.Results:The median follow-up of all patients was 46.0 months (range: 19.5-88.0 months), the 3-year DFS was 79.2%, and the 3-year OS was 87.4%. Univariate analysis found that the NAR score had a significant impact on the 3-year DFS and OS. The 3-year DFS of patients with low, medium, and high NAR scores were 90.3%, 86.1% and 58.7% ( P<0.001), and the 3-year OS were 94.4%, 91.7% and 74.6%, ( P<0.001), respectively. Subgroup analysis showed that the predictive value of the NAR score also applied to the strengthened neoadjuvant therapy model. The 3-year DFS of patients with low, medium, and high NAR scores were 86.9%, 83.8% and 68.3% ( P=0.044), and the 3-year OS were 92.9%, 90.7% and 85.4% ( P=0.029), respectively. Conclusion:The NAR score can effectively predict the prognosis of patients with middle and low locally advanced rectal adenocarcinoma, whether using neoadjuvant therapy or strengthened neoadjuvant therapy followed by TME surgery.

Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.

Objective:To explore and verify the value of neoadjuvant rectal (NAR) score in predicting the prognosis of patients with middle and low locally advanced rectal cancer.Methods:A retrospective analysis of 207 patients with middle and low locally advanced rectal adenocarcinoma who received neoadjuvant radiotherapy and chemotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2015 to December 2021 was performed. The neoadjuvant radiotherapy regimen was pelvic external irradiation of 45-50.4 Gy, 1.8 Gy/f, 5 times per week and concurrent oral capecitabine chemotherapy on days 1-14 and 22-36 during radiotherapy. Total mesorectal excision (TME) was then performed. The NAR score was calculated based on the initial clinical stage and postoperative pathological stage, and divided into the low (<8), medium (8-16) and high (>16) layers, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences in DFS and OS among different NAR score layers were compared using the log-rank test. Some patients received consolidation chemotherapy during the interval between concurrent radiotherapy-chemotherapy and surgery, even the total neoadjuvant therapy (TNT) model. Subgroup analysis was further used to verify the predictive value of the NAR score in the strengthened neoadjuvant therapy model.Results:The median follow-up of all patients was 46.0 months (range: 19.5-88.0 months), the 3-year DFS was 79.2%, and the 3-year OS was 87.4%. Univariate analysis found that the NAR score had a significant impact on the 3-year DFS and OS. The 3-year DFS of patients with low, medium, and high NAR scores were 90.3%, 86.1% and 58.7% ( P<0.001), and the 3-year OS were 94.4%, 91.7% and 74.6%, ( P<0.001), respectively. Subgroup analysis showed that the predictive value of the NAR score also applied to the strengthened neoadjuvant therapy model. The 3-year DFS of patients with low, medium, and high NAR scores were 86.9%, 83.8% and 68.3% ( P=0.044), and the 3-year OS were 92.9%, 90.7% and 85.4% ( P=0.029), respectively. Conclusion:The NAR score can effectively predict the prognosis of patients with middle and low locally advanced rectal adenocarcinoma, whether using neoadjuvant therapy or strengthened neoadjuvant therapy followed by TME surgery.

Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.

Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Mice ; Animals ; Micrognathism ; Masseter Muscle ; Mandible ; Osteogenesis

Objective:To compare the efficacy of pericapsular nerve group (PENG) block combined with lateral femoral cutaneous nerve (LFCN) block versus fascia iliaca compartment block (FICB) in elderly patients undergoing total hip arthroplasty under general anesthesia.Methods:Fifty-eight patients of both sexes, aged 65-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective direct anterior approach to total hip arthroplasty, were divided into 2 groups ( n=29 each) using a random number table method: PENG block plus LFCN block group (PL group) and FICB group (F group). In group PL, the mixture (20 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 3.3 mg was injected around the nerve innervating the hip joint capsule under ultrasound guidance.In group F, the mixture (30 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 5 mg was injected around the nerve innervating the fascia iliaca compartment under ultrasound guidance.All the patients received patient-controlled intravenous analgesia with oxycodone after surgery.When visual analogue scale scores≥4 points, oxycodone 1 mg was intravenously injected as rescue analgesic.The intraoperative consumption of remifentanil was recorded.First time to ambulation, discharge destination, length of hospital stay, and effective pressing times of analgesic pump, requirement for rescue analgesia and the incidence of quadriceps weakness, nausea and vomiting and nerve block related complications within 48 h after surgery were recorded. Results:Compared with F group, intraoperative consumption of remifentanil was significantly decreased, effective pressing times of analgesic pump and incidence of quadriceps weakness were decreased, first time to ambulation and length of hospital stay were shortened, and first discharge destination was prolonged ( P<0.05), and no significant change was found in the requirement for rescue analgesia and the incidence of nausea ( P>0.05) in group PL. Conclusion:PENG block combined with LFCN block can reduce intraoperative consumption of opioids, be helpful for inhibiting postoperative pain sensitivity, and improve early recovery than FICB when used for total hip arthroplasty under general anesthesia.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective To explore the nursing effect of modified prone position and traditional prone position in the skin protection of patients with prone position in ICU. Methods A total of 60 ICU patients with prone position treatment were selected in June 2014 to May 2015. According to the digital method the patients were randomly divided into the control group and the experimental group with 30 cases in each.The control group adopted traditional way of prone position with the head and chest pad pushed up. used by patients not pad up way of improvement of prone position. The incidence of skin pressure injury and the incidence of stress in the two groups were compared. Results The incidence of skin pressure injury was 20.0％(6/30) in the experimental group and 66.7％(20/30) in the control group, and the difference was statistically significant (χ2=13.30, P < 0.05). Conclusions Modified prone position has obvious advantages in reducing the incidence of skin pressure ulcer and is suitable for patients with clinical prone position.

Objectives To implement the guideline-based clinical practice program for identification and manage-ment of dysphagia in stroke patients,and to create a good evidence-based practice culture,and to improve the quality of clinical care. Methods In this study,we use the Iowa model of evidence-based practice as a guide, reference guide issued by RNAO to implement the corresponding implementation strategy tool,and gradually apply the program to the pilot ward. Results The implementation of the program had a positive impact on the patient level (quality of life,satisfaction and hospitalization),the nurse level(satisfaction and knowledge),and the level of eachau-ditcriteria. Conclusion It is possible to improve the clinical nursing quality by adapting the high quality guide-lines for the identification and management of dysphagia in foreign countries and this study can provide reference for the research of future guideline implementation.