Background and purpose:With the progressive development of breast cancer surgery toward more individualized and minimally invasive approaches,sentinel lymph node biopsy(SLNB)has replaced axillary lymph node dissection(ALND)as the standard method for axillary management in certain early-stage breast cancer patients.However,there is ongoing debate in clinical practice regarding whether regional lymph node irradiation(RNI)is necessary for patients with sentinel lymph node(SLN)positive status who have not undergone ALND.This study aimed to analyze the clinicopathological features and survival prognosis of patients with SLN-positive status who did not undergo ALND,evaluate the clinical application value of RNI,and provide evidence to support clinical treatment decisions for this group of patients.Methods:This single-center retrospective study screened breast cancer patients who underwent SLNB at Shandong Cancer Hospital from September 1,2014,to August 31,2023.All patients signed informed consent for treatment.Based on whether postoperative radiotherapy included regional lymph node irradiation(internal mammary and/or axillary and/or supra-/infra-clavicular fields),patients were divided into the RNI group and the no-RNI group for follow-up.Additionally,patients were further divided into multiple subgroups based on factors such as the type of breast surgery,tumor molecular subtype,and histological grade,to compare the clinical value of RNI among subgroups.The primary endpoint was locoregional recurrence-free survival(LRRFS),and the secondary endpoints included invasive disease-free survival(iDFS)and overall survival(OS).The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:Clinical data of 8 328 breast cancer patients'were screened for this study,and after applying inclusion and exclusion criteria,356 patients were included in the analysis,with 186 in the RNI group and 170 in the no-RNI group.There were no significant differences between the two groups in terms of age,body mass index(BMI),menopausal status,tumor location,pathological type,histological grade,vascular invasion,estrogen receptor(ER)and progesterone receptor(PR)status,and human epidermal growth factor receptor 2(HER-2)expression(P＞0.05).However,the number of positive SLNs,T stage,and the proportion of patients undergoing total mastectomy(TM)were significantly higher in the RNI group than in the no-RNI group(P=0.006,P=0.043,P＜0.001).After a median follow-up of 38 months,no recurrence or metastasis was observed in the RNI group,while the recurrence and metastasis rate in the no-RNI group was 3.5%(6/170).Of these,4 cases had local regional recurrence,and 2 had distant metastasis.The RNI group showed superior iDFS compared to the no-RNI group(P=0.017),however there was no statistically significant difference in LRRFS and OS(P=0.051 and P=0.356).Exploratory subgroup analysis indicated that patients with tumor diameter＞2 cm(P=0.033)and triple-negative molecular(TNBC)(P=0.020)might benefit from RNI treatment in terms of LRRFS.Conclusion:For certain high-risk patients,such as those with larger tumor diameter,TNBC,or high non-SLN metastatic risk,RNI still plays an important role in reducing the risk of recurrence and metastasis in breast cancer.In clinical practice,an individualized RNI strategy should be developed based on the patient's residual lymph node tumor load,biological behavior of the tumor,and surgical method.

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

In order to establish a serological method for the detection of bovine respiratory syncytial virus,the prokaryotic expression of four proteins of BRSV,G,F,P,and M was carried out,and the most suitable coating antigen was screened to establish an indirect ELISA detection method.The results showed that the four recombinant proteins of BRSV,rG,rF,rP and rM were successfully expressed.The results of checkerboard screening showed that the P/N value of rG protein was the largest,which was determined to be the best coating antigen established by indirect ELISA meth-od.The optimal reaction conditions for indirect ELISA were as follows:the mass concentration of rG protein coating was 1 mg/L,37℃ for 2 h;3％BSA 37℃ block for 1 h;Serum was diluted 1∶50 and incubated at 37℃ for 1h;Secondary antibody 1∶5 000 dilution,37℃ for 30min;The color development conditions of the substrate were 37℃ for 15 min;Thirty negative sera were selected,and the cut-off value was determined to be 0.63 by the established indirect ELISA method.The re-sults of the specificity test showed that the indirect ELISA method established in this test only recognized BRSV-positive serum,and did not react with IBRV,BCoV,and BPIV3-positive serum.The results of repeatability test showed that the method had good repeatability,and the coefficient of variation within and between batches was less than 10％.The results of the sensitivity test showed that the BRSV-positive serum was still positive when diluted to 1∶8 192.The indirect ELISA method established in this experiment was used to detect 100 clinical serum samples at the same time,and the total coincidence rate of the two reached 90.48％,the positive coincidence rate was 93.42％,and the negative coincidence rate was 82.75％.The indirect ELISA established in this test can be used for the detection of bovine respiratory syncytial virus in clinical practice.

Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P＜0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.

Objective To evaluate the efficacy of arthroscopic double row suture technique combined with knotless suture bridge technique in repairing medium and large rotator cuff tears.Methods 92 medium and large rotator cuff tears patients from January 2018 to October 2022 were randomly divided into two groups with 46 cases in each group.The observation group was administrated with arthroscopic double row suture combined with knotless suture bridge technique,while the control group was treated with arthroscopic single row suture combined with knotless suture bridge technique.The two groups were compared before and 3,6,and 12 months after surgery in terms of intermediate,medial and lateral T2 values of supraspinatus tendons,shoulder joint range of motion,and the scores on related scales[Constant-Murley scale,University of California,Los Angeles(UCLA)shoulder joint grading system,visual analogue scale(VAS)score],as well as the acromion-humeral head distance(A-H distance).And the joint stiffness and rotator cuff tears were collected from the two groups within 12 months after the operation.Results At 3,6 and 12 months after surgery,the intermediate,medial and lateral T2 values of supraspinatus tendons in both groups were gradually decreased,and were significantly lower than those before surgery,the differences were statistically significant(P<0.05),and the intermediate,medial and lateral T2 values of supraspinatus tendons at each time point in the observation group were significantly lower than those in the control group,the differences were statistically significant(P<0.05);At 3,6,and 12 months after surgery,the anterior flexion range of motion,lateral rotation range of motion,and A-H head distance of both groups were seeing a gradual increase,and the values were significantly higher than those before the treatment,the differences were statistically significant(P<0.05).The anterior flexion range of motion,lateral rotation range of motion and A-H head distance at each time point in the observation group were significantly greater than those in the control group,the differences were statistically significant(P<0.05);At 3,6,and 12 months after surgery,the Constant-Murley and UCLA scales of both groups were seeing a gradual increase,and the values were significantly higher than those before the treatment,the differences were statistically significant(P<0.05),and The Constant-Murley and UCLA scales of the observation group at each time point were significantly higher than those of the control group,the differences were statistically significant(P<0.05);At 3,6,and 12 months after surgery,the VAS score in both groups was lower than that before operation,the difference was statistically significant(P<0.05),the VAS score of the observation group at 3 months after surgery was significantly lower than that of the control group,the difference was statistically significant(P<0.05);12 months after surgery,the incidence of joint stiffness and rotator cuff retear in observation group were 2.17%and 0.00%,significantly lower than those in control group(17.39%and 13.04%),the differences were statistically significant(P<0.05).Conclusion The application of arthroscopic double row suture combined with knotless suture bridge technique can effectively promote postoperative rotator cuff tissue healing,improve the range of motion,function of the shoulder joint and A-H head distance,relieve shoulder pain and greatly reduce the occurrence of postoperative rotator cuff tear and joint stiffness compared with arthroscopic single row suture combined with knotless suture bridge technique.It is worthy clinical application.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

In order to establish a serological method for the detection of bovine parainfluenza virus type 3(BPIV3),the prokaryotic expression and purification of BPIV3 HN,NP,F,and P proteins were carried out,and the optimal protein-coated antigen was screened,and an indirect ELISA de-tection method was established.The results showed that the four recombinant proteins of BPIV3,rHN,rNP,rF,and rP were expressed,and the checkerboard titration results showed that rHN pro-tein had the highest P/N value as the coating protein,so it was used for the subsequent method es-tablishment.The optimal reaction conditions for indirect ELISA were found to be:the mass con-centration of the antigen coating was 0.5 mg/L,37 ℃ 1.5 h,5％skim milk,overnight blocking at 4 ℃,serum dilution at 1∶50,incubation at 37 ℃ 1 h,secondary antibody dilution at 1∶10 000 and incubation at 37℃ 0.5 h,substrate reaction conditions were 37℃ for 12 min.The results of speci-ficity experiments showed that the established method could specifically identify BPIV3 antibody-positive serum with a sensitivity of 1∶800,and the coefficient of variation in the detection of intra-and inter-assay repeatability was less than 10％,and the overall coincidence rate of the same batch of samples detected with the SVANOVIR kit was 92.22％.This method was used to detect 192 se-rum samples in Hebei Province,and the positive rate of BPIV3 antibody in serum was 66.15％.The indirect ELISA detection method of BP1V3 antibody constructed in this study is suitable for large-scale clinical serological investigations,and provides valuable data support for the research and de-velopment of BPIV3 antigen and antibody detection kits in China.

In order to investigate the role of sRNA OxyS in the pathogenicity of Salmonella typhi-murium infection,the OxyS gene deletion strain ATCC25241 △OxyS and the back-complemented strain ATCC25241 △OxyS/OxyS of Salmonella typhimurium ATCC25241 were constructed by using λRed homologous recombination technique.We investigated the effect of OxyS deletion on the biological characteristics and pathogenicity of Salmonella typhimurium ATCC25241.The re-sults showed that the deletion of OxyS did not affect the growth rate,the ability of biofilm forma-tion,and the ability of adhesion,invasion and intracellular survival of Salmonella typhimurium,but significantly reduced the motility of Salmonella typhimurium as well as its ability to survive in alkaline and oxidative environments.The results of mouse infection test showed that OxyS dele-tion caused a significant decrease in the virulence of Salmonella typhimurium in mice,and toxicity is reduced obviously.The qPCR results also showed that OxyS deletion could lead to changes in the transcript levels of a number of virulence-related genes of Salmonella typhimurium such as pipB,orf245,csgA,invH,tatA,sipA,sipB,and so on.The above results indicate that OxyS gene affects the biological characteristics and pathogenicity of Salmonella typhimurium and is an important virulence regulator of Salmonella typhimurium.

Background and purpose:With the progressive development of breast cancer surgery toward more individualized and minimally invasive approaches,sentinel lymph node biopsy(SLNB)has replaced axillary lymph node dissection(ALND)as the standard method for axillary management in certain early-stage breast cancer patients.However,there is ongoing debate in clinical practice regarding whether regional lymph node irradiation(RNI)is necessary for patients with sentinel lymph node(SLN)positive status who have not undergone ALND.This study aimed to analyze the clinicopathological features and survival prognosis of patients with SLN-positive status who did not undergo ALND,evaluate the clinical application value of RNI,and provide evidence to support clinical treatment decisions for this group of patients.Methods:This single-center retrospective study screened breast cancer patients who underwent SLNB at Shandong Cancer Hospital from September 1,2014,to August 31,2023.All patients signed informed consent for treatment.Based on whether postoperative radiotherapy included regional lymph node irradiation(internal mammary and/or axillary and/or supra-/infra-clavicular fields),patients were divided into the RNI group and the no-RNI group for follow-up.Additionally,patients were further divided into multiple subgroups based on factors such as the type of breast surgery,tumor molecular subtype,and histological grade,to compare the clinical value of RNI among subgroups.The primary endpoint was locoregional recurrence-free survival(LRRFS),and the secondary endpoints included invasive disease-free survival(iDFS)and overall survival(OS).The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:Clinical data of 8 328 breast cancer patients'were screened for this study,and after applying inclusion and exclusion criteria,356 patients were included in the analysis,with 186 in the RNI group and 170 in the no-RNI group.There were no significant differences between the two groups in terms of age,body mass index(BMI),menopausal status,tumor location,pathological type,histological grade,vascular invasion,estrogen receptor(ER)and progesterone receptor(PR)status,and human epidermal growth factor receptor 2(HER-2)expression(P＞0.05).However,the number of positive SLNs,T stage,and the proportion of patients undergoing total mastectomy(TM)were significantly higher in the RNI group than in the no-RNI group(P=0.006,P=0.043,P＜0.001).After a median follow-up of 38 months,no recurrence or metastasis was observed in the RNI group,while the recurrence and metastasis rate in the no-RNI group was 3.5%(6/170).Of these,4 cases had local regional recurrence,and 2 had distant metastasis.The RNI group showed superior iDFS compared to the no-RNI group(P=0.017),however there was no statistically significant difference in LRRFS and OS(P=0.051 and P=0.356).Exploratory subgroup analysis indicated that patients with tumor diameter＞2 cm(P=0.033)and triple-negative molecular(TNBC)(P=0.020)might benefit from RNI treatment in terms of LRRFS.Conclusion:For certain high-risk patients,such as those with larger tumor diameter,TNBC,or high non-SLN metastatic risk,RNI still plays an important role in reducing the risk of recurrence and metastasis in breast cancer.In clinical practice,an individualized RNI strategy should be developed based on the patient's residual lymph node tumor load,biological behavior of the tumor,and surgical method.

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.