BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective To investigate the clinical utility of ultrasound parameters in diagnosing neonatal annular pancreas.Methods A total of 56 neonates with descending duodenal obstruction underwent saline-contrast ultrasound examination.Ultrasonic parameters,including dilated duodenum diameter(DDD),dilated duodenum thickness(DDT),and stenosis duodenum diameter(SDD),were measured.The cases were categorized into three groups:annular pancreas(group A,n=28),descending duodenal atresia(group B,n=3),and descending duodenal septum(group C,n=25).One-way ANOVA was employed to compare statistical differences among the three ultrasonic parameters across the groups,followed by LSD-t test for pairwise comparisons between two groups showing significant differences.Receiver operating characteristics analysis was conducted to calculate the area under the curve and determine the cut-off value if there were statistically significant differences observed.Results In group A,group B,group C,the diameters of DDD were measured as(23.2±2.4)mm,(25±1.0)mm,(19.4±2.6)mm,respectively.When comparing these three groups,there was a statistically significant difference between group A or group B and group C in terms of DDD diameter measurements(t=5.7,P＜0.05;t=3.793,P＜0.05).However,no statistically significant difference was observed between group A and group B for DDD diameter measurements(t=1.232,P＞0.05).The corresponding values for DDT were measured as(3.0±0.6)mm,(3.2±0.4)mm,and(2.4±0.3)mm,respectively.When comparing these three groups,the results showed a statistically significant differ-ence between either Group A or Group B compared to Group C in terms of DDT measurement(t=4.695,P＜0.05;t=2.778,P＜0.05).However,no statistically significant difference was found between Group A and Group B regard-ing the measurement of DDT(t=0.666,P＞0.05).The SDD measurements in the three groups were(1.9±0.3)mm,(3.6±0.8)mm,(5.5±0.7)mm,respectively.Statistical analysis using LSD-t test revealed significant differences between the three groups(t=5.521,P＜0.05;t=6.142,P＜0.05;t=25.828,P＜0.05).The sensitivity,specificity,positive predictive value,and negative predictive value for detecting annular pancreas at a cutoff of 2.3 mm were determined to be 96.4%,100%,100%,and 96.6%,respectively,with an area under the receiver operating charac-teristic curve of 0.999.Conclusion SDD could be employed for the diagnosis of neonatal annular pancreas.

Purpose To evaluate the value of MRI T1 mapping combined with biliary tract paravertebral muscle signal intensity ratio in liver function.Materials and Methods A total of 72 patients with Gd-EOB-DTPA enhanced MRI were prospectively collected in Beijing Friendship Hospital from August 2020 to February 2022 and divided into three groups according to Child-Pugh classification of liver function:22 patients in normal liver function group,35 patients in grade A group and 15 patients in grade B+C group.The T1 mapping sequence was scanned in all patients before and 20 min after enhancement to measure the pre-enhancement and post-enhancement(T1post)T1 relaxation time of liver parenchyma,and the reduction rate of liver T1 relaxation time(ΔT1)was calculated.Biliary tract signal and paravertebral muscle signal were measured on hepatobiliary stage images,and biliary tract paravertebral muscle signal intensity ratio(SIR)was calculated.The consistency of measurement results among physicians was evaluated.The correlation between each index and liver function grade was observed.The differences among different groups were compared.The diagnostic efficiency of each image index were evaluated.Results T1post was positively correlated with liver function grade(r=0.683,P<0.001),and it increased gradually with the severity of liver function impairment.ΔT1,SIR,SIR×ΔT1 were negatively correlated with liver function grade(r=-0.764,-0.729,-0.826,all P<0.001),and gradually decreased with the severity of liver function impairment.T1post,ΔT1,SIR,SIR×ΔT1 had statistical significance in liver function classification among all groups(F=27.491,55.782,48.410,46.809,all P<0.05).In pairwise comparison,the differences of each index were also statistically significant(P<0.05).The best diagnostic efficacy of each index was SIR×ΔT1,and the area under the curve of normal liver function group and cirrhosis group,grade A group and grade B+C group were 0.915 and 0.984,respectively.Conclusion T1post,ΔT1,SIR and SIR×ΔT1 are strongly correlated with Child-Pugh grade of liver function.SIR×ΔT1 can be used as an imaging index for quantitative evaluation of liver function.

Objective:To investigate the factors affecting the change of serum calcium and phosphorus after total parathyroidectomy for secondary hyperparathyroidism(SHPT).Method:Sixty patients with secondary hyperparathyroidism undergoing total parathyroidectomy were selected.Gender, age, hemodialysis time, bone pain time, intravenous calcium supplementation time, blood parathyroid hormone(PTH), parathyroid mass, blood calcium, phosphorus and alkaline phosphatase at admission were tested to compare the correlation between postoperative calcium and phosphorus changes.Result:Blood calcium was: (2.50±0.02), (2.27±0.03), (1.97±0.03), (1.95±0.03), (1.95±0.03), (2.03±0.02) mmol/L at admission, 6 hours after surgery, 1, 2, 3 days after surgery, and when discharged. Blood phosphorus was: (2.32±0.07), (1.95±0.05), (1.65±0.06), (1.44±0.05), (1.35±0.36), (1.14±0.04) mmol/L and when discharged.There are differences between pairwise comparisons ( F=100.979, P<0.05; F=118.910, P<0.05). The blood PTH was (1 791±760) pg/ml, and the postoperative intravenous calcium supplementation time was (7.13±2.34) days. Blood PTH was positively correlated with bone pain time, blood phosphorus and parathyroid mass at admission ( t=-2.199, P<0.05; t=4.718, P<0.05; t=2.507, P<0.05). The time of intravenous calcium supplementation was positively correlated with ALP at admission ( t=3.098, P<0.05). Preoperative serum PTH > 1 430 pg/ml or ALP > 191 mmol/L were prone to hypocalcemia on the first day after surgery. Conclusions:The longer bone pain time, the higher blood phosphorus and the more obvious parathyroid hyperplasia were, the higher PTH was. The higher the ALP, the longer the time of intravenous calcium supplementation. Preoperative serum PTH and ALP values can be used as predictors of hypocalcemia on the first day after surgery.

Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the sec-ondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus(HPV)and subjected to thin-prep cytologic test(TCT)and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24％and the specificity of 23.75％for detecting cervical intraepithelial neoplasia(CIN)grade 2 and above(CIN2+).After the addition of the SOX1/PAX1 gene methylation detection in secondary triage,the sensitivity for detecting CIN2+was 83.33％,which had no statistically significant difference from the sensitivity of TCT combined with HPV test(P=0.078).However,the specificity reached 77.50％,which was significantly higher than that of HPV test combined with TCT(P＜0.001).The SOX1/PAX1 gene methylation level in the CIN2+group was higher than those in the normal cervical tissue and the CIN1 group(P＜0.001).The cut-off values of SOX1 and PAX1 gene methylation for CIN2+detection were-11.81 and-11.98,respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+detection.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To investigate the factors related to recurrent laryngeal nerve invasion in papillary thyroid carcinoma (PTC) with posterior capsular involvment.Methods:The data of 186 PTC patients admitted and operated from Jun 2017 to Jun 2022 were retrospectively analyzed. The invasion of recurrent laryngeal nerve was evaluated on its relation to gender, age, tumor size, Hashimoto's thyroiditis, lymph node metastasis in central region, BRAFV600E gene mutation especially PTC posterior capsular involvement.Results:The recurrent laryngeal nerve was invaded in 30 out of 186 patients. Univariate analysis showed that recurrent laryngeal nerve invasion was related to tumor size, Hashimoto's thyroiditis and cervical lymph node metastasis( χ2=6.964,4.814,6.078, P<0.05). Multivariate regression analysis showed that tumor size and lymph node metastasis in cervical region were independent risk factors for recurrent laryngeal nerve invasion(β=1.020,1.622, P<0.05). Hashimoto's thyroiditis was a protective factor for recurrent laryngeal nerve invasion (β=-1.881, P<0.05). Conclusions:When papillary thyroid carcinoma invaded the capsule, the risk of recurrent laryngeal nerve invasion was higher with larger tumor size and cervical lymph node metastasis, while Hashimoto's thyroiditis was a protective factor for the risk of recurrent nerve invasion.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

ObjectiveTo investigate rehabilitation competence among trainers and trainees whom participated in the training program entitled National Training Program of Shortage Rehabilitation Physicians (NTPSRP) using World Health Organization rehabilitation competency framework (RCF). MethodsBased on RCF, a questionnaire was developed and administrated through network using Questionnaire Star. All the trainers and trainees who participated in NTPSRP were investigated in September, 2023. ResultsA total of 911 subjects were collected from 27 provinces, including 426 trainers (teachers) and 485 trainees (students). The average age of the teachers was older, with more years of work experience and professional experience in rehabilitation medicine. The degree and professional title of the teachers was also higher. The overall internal consistency reliability of the questionnaire was good (Cronbach's α = 0.988), and all the internal consistency reliability in five fields was good (Cronbach's α > 0.9). The five dimensional structure of RCF in the results was consistent with the prior model established by RCF theory. The self-ratings of all physicians in the five fields were higher than the median level, and was higher in the teachers than in the students [(3.42±0.68) vs. (2.73±0.80), P < 0.001]. Gender and years of experience in rehabilitation medicine were independent factors for the total score of the questionnaire. The total self-rating of female students was 9.65 points lower than that of the male (95%CI 4.386 to 14.914); and one more year in rehabilitation medicine would increase 1.78 points in self-rating (95%CI 1.140 to 2.419). ConclusionThe structure and content of RCF can be used to evaluate the competence of rehabilitation physicians. The teachers and students of NTPSRP are eligible to RCF. RCF-based evaluation can be used to guide the development of continuing education courses for rehabilitation professionals.