Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

Objective To investigate the current status of knowledge,attitude,and practice(KAP)re-garding the clinical application of graduated compression stockings(GCS)for preventing venous thromboem-bolism(VTE)among medical staff and analyze its influencing factors.Methods Through convenience sam-pling,5 706 medical staff from 85 hospitals in Chongqing were surveyed using the"Questionnaire on KAP of Clinical Application of GCS for VTE Prevention"between March 16 and 30,2024.Univariate and multiple lin-ear stepwise regression analyses were conducted to explore influencing factors.Results The scores for knowl-edge,attitude,and practice in the clinical application of GCS for VTE prevention among healthcare workers were(37.77±10.56),(16.85±3.05),and(24.85±7.51),respectively.Age,highest education level,seniori-ty,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombosis prevention center certification,and GCS procurement channels were influen-cing factors for knowledge scores.Professional title,whether they had received GCS application training,hos-pital level,and whether the hospital passed the national venous thrombosis prevention center certification were influencing factors for attitude scores.Gender,age,highest education level,seniority,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombo-sis prevention center certification,and GCS procurement channels were influencing factors for behavior scores.Conclusion Healthcare workers'knowledge of clinical application of GCS for VTE prevention is at a medium level,their attitude toward clinical application is positive,and practical behaviors are basically in compliance with standards.Hospital managers should emphasize training and assessment on clinical application of GCS for healthcare workers,strengthen quality control in practical implementation,and ensure patients receive stand-ardized mechanical VTE prevention.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left atrial function in normal fetuses and fetuses with left ventricular outflow tract obstruction (LVOTO).Methods:A total of 32 fetuses diagnosed with LVOTO, who underwent fetal echocardiography at Sir Run Run Shaw Hospital, Zhejiang University College of Medicine between May 2020 to June 2022, were selected as the case group, and 100 pregnant women with normal singleton fetuses between January 2019 to October 2022 were chosen as the control group. The standard basal or apical four-chamber view clips were obtained and were quantitatively analyzed using TomTec-Arena off-line cardiac analysis software to obtain the left atrial strain parameters of the two groups of fetuses including left atrial reservoir phase longitudinal strain(LASr), left atrial ductal phase longitudinal strain(LAScd), left atrial systolic phase longitudinal strain (LASct), as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of the two groups: biparietal diameter (BPD), femur length (FL), aortic annulus end-systolic inner diameter (AO), pulmonary annulus end-systolic inner diameter (PA), left atrial end-systolic long length (LAESL), left atrial end-systolic transverse diameter (LAESD), right atrial end-systolic long length (RAESL), right atrial end-systolic transverse diameter (RAESD), left ventricular end-diastolic transverse diameter (LVEDD) and right ventricular diastole end-diastolic transverse diameter (RVEDD). The ratio of right ventricular end-diastolic transverse diameter to left ventricular end-diastolic transverse diameter (RVd/LVd) and the ratio of pulmonary annulus diameter to aortic annulus diameter (PA/AO) were calculated. The differences of strain parameters between the two groups were compared, and the correlation between strain parameters and gestational age, RVd/LVd and other conventional measurement parameters were analyzed. ROC curve was used to compare the specificity and sensitivity of LASr and RVd/LVd in evaluating fetal cardiac dysfunction with LVOTO.Results:There were significant differences in LASr, LAScd, LASct, MAPSE, AO, LAESL, LVEDD, RVd/LVd and PA/AO between the two groups (all P<0.05), there were no significant differences in other parameters (all P>0.05). Correlation analysis showed that LASr was negatively correlated with RVd/LVd in LVOTO group ( rs=-0.394, P=0.025), and LASct was negatively correlated with RVd/LVd ( rs=-0.626, P=0.004). In the control group, LASr was negatively correlated with gestational age, AO and PA ( r/ rs=-0.570, -0.440, -0.493; all P<0.001), and LASct was negatively correlated with gestational age, AO and PA ( r/ rs=-0.601, -0.532, -0.568; all P<0.001). LAScd was positively correlated with gestational age, AO and PA ( r/ rs=0.310, 0.370, 0.314; all P<0.05). There were no significant correlations between the other parameters (all P>0.05). ROC curve analysis showed that the area under the curve(AUC) in LASr evaluation of fetal cardiac dysfunction with LVOTO was 0.890 (0.826, 0.953) and the AUC in RVd/LVd evaluation of fetal cardiac dysfunction with LVOTO was 0.742 (0.637, 0.846), there were significant differences between them( P<0.05). Conclusions:2D-STE is highly feasible and reproducible in assessing fetal left atrial function. Evaluation of fetal left atrial function by 2D-STE provides a new reference index for quantitative analysis of fetal cardiac dysfunction.

Objective To construct the medical risk comprehensive assessment system based on big data,and to evaluate its consistency and efficiency.Methods Aiming at the current situation of risk assessment of inpatients,based on the means of big data,the medical natural language processing was used to design a medi-cal risk comprehensive assessment system.The system can automatically capture various data of patients,au-tomatically generate the scores by data mining and machine learning technology and send the risk data to med-ical staff,so as to realize the automation and intellectualization.The randomized controlled analysis was used to conduct the manual scoring and machine scoring for included the score scale.The visual risk matrix diagram was automatically generated by comparing the scoring.Results The Kappa values of the scoring system in the included study of the system were as follows:the Kappa value in Caprini scale(surgery)and Padua scale(internal medicine)was 1.00,NNIS Kappa value was 1.00,Nomogram Kappa value was 0.87,Kappa value in the Morse assessment scale/Hendrich model was 0.83,Braden Kappa value was 0.80,ASA 2023 Kappa was 1.00 and NRS 2002 Kappa value was 0.90.The taking time in the machine scoring all were shorter than those in the manual scoring,and the difference was statistically significant(P＜0.05).Conclusion The risk matrix graph constructed by this system could sharply increase the evaluation efficiency and accuracy,which not only provide the accuracy diagnosis and treatment regimen,but also shorten the hospitalization duration and reduce the medical costs.

An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.

Objective To analyze the characteristics of military training injuries of cadets in a military academy,so as to provide a basis for preventing military training injuries.Methods A questionnaire surgery was performed in 911 cadets in a military academy to investigate the military training injuries.The general situation,training situation,and training injuries of the respondents were analyzed.Results The incidence of military training injuries was 39.51%(360/911).There were 243 cases of mild injuries,111 cases of moderate injuries,and 6 cases of severe injuries.Long-distance running and cross-country training(160 cases,44.44%),equipment assessment(55 cases,15.28%),and obstacle race(33 cases,9.17%)were main high-risk trainings.The knee(141 sites,28.48%),foot(119 sites,24.04%),and lower leg(57 sites,11.52%)were the high-risk injury sites of training injuries.Univariate analysis of risk factors for training injuries showed that the incidence of training injuries in urban students was significantly higher than that in non-urban students(P<0.05).No exercise preference or foundation,no warm-up before training,no mastery of core muscle strength training content,core muscle strength training time≤30 min,no relaxation after training,and no relaxation skills after training were risk factors for training injuries(P<0.05).Logistic regression analysis showed that urban origin,no sports preference or foundation,no warm-up before training,no mastery of core strength training content,core strength training time≤30 min,no relaxation after training,and no relaxation skills after training were independent risk factors of training injury.Conclusion The incidence of military training injuries is high in cadets.More attention should be paid to cadets who are from urban,or had no exercise proference or foundation,no warm-up before training,no mastery of core muscle strength training content,core muscle strength training time≤30 min,no relaxation after training,or no relaxation skills after training.

Objective:To construct the quality evaluation system for tracheal extubation in the patients undergoing general anesthesia based on zero-defect management theory.Methods:Based on the model of zero-defect theory, literature review, semi-structured interviews, expert consultation and analytic hierarchy process were used to determine the content and weight of each index of the quality evaluation system for tracheal extubation in the patients undergoing general anesthesia.Results:The effective recovery rates of the two rounds of expert consultation questionnaires were 93% and 96% respectively; the expert authority coefficients were 0.946 and 0.947 respectively; the Kendall harmony coefficients were 0.247 and 0.250 respectively ( P<0.001). The final evaluation index system included 3 first-level indicators, 11 second-level indicators and 48 third-level indicators.The consistency coefficients of indicators at all levels were <0.1. Conclusions:The quality evaluation system for endotracheal extubation constructed for patients undergoing general anesthesia is highly scientific and reliable and can provide a basis for the quality evaluation of and continuous improvement in endotracheal extubation in the patients undergoing general anesthesia.

OBJECTIVES: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing. METHODS: A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme. RESULTS: With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC. CONCLUSIONS The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.
Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Immunohistochemistry ; Lung Neoplasms/genetics* ; Mutation