Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective: To determine the heterogeneity for caries prevention service preferences among children in Anhui Province, so as to provide reference for the promotion and popularization of caries prevention services for school age children. Methods: Based on a discrete selection experiment, a face to face questionnaire survey was administered using a multi stage sampling method among 785 parents with children 3-12 years of age who were hospitalized in the stomatology clinics of 7 prefectures and cities in Anhui Province from October 2021 to October 2022. A mixed Logit model was used to evaluate caries prevention service preferences for children. Results: Four discrete choice experiment attributes included in the study were statistically significant for choice preference ( P <0.05). Compared with the control group, parents with a high school education or above preferred caries prevention services with 70%-<80% preventive effectiveness, 2-<5 and <2 km from the service point, and a high service cost ( β =0.38, 1.66, 1.64, 0.00); female parents preferred preventive services with 70%-<80% preventive effectiveness and a high service cost ( β =0.35, 0.01 ); parents of children <7 years of age preferred services with 70%-<80% preventive effectiveness ( β =0.75); parents of children with oral health preferred preventive services during winter and summer vacations ( β =-0.28); parents of children with caries preferred preventive services with a high cost per denticle ( β =0.00)( P <0.05). Conclusions Parents with different education levels, gender, child age, and oral health status have heterogeneity in dental caries prevention service preferences. The provision of targeted and precise services can improve the participation and coverage of caries prevention services for school age children.

ObjectiveTo determine the resistance of adult Culex quinquefasciatus and Musca domestica to commonly used insecticides in Dazhu District of Chongqing in 2023， and provide scientific evidence for rational use of hygienic insecticides. MethodsDrug resistance was determined by using adult mosquito contact tube method and adult fly drop method. ResultsIn 2023， the 24-hour mortality rate of adult Culex quinquefasciatus in Dazu District， Chongqing， against permethrin （0.25%）， beta-cypermethrin （0.025%）， deltamethrin （0.025%）， malathion （5%） and propoxur （0.1%） was 37.35%， 21.92%， 28.33%， 96.43%， and 95.38%， respectively. The median lethal dose （LD₅₀） value of female adult Musca domestica against beta-cypermethrin （95.8%）， chlorpyrifos （97%）， deltamethrin （90%） and dichlorvos （95%） was 2.572 μg， 0.329 μg， 0.406 μg， and 0.492 μg， respectively， with resistance of 829.68， 7.65， 53.42， and 46.42 folds to the above tested insecticides． ConclusionAdult Culex quinquefasciatus and Musca domestica in Dazu District show various degrees of resistance to commonly used insecticides. It warrants suspending the insecticides with high resistance， whereas mixedly and alternatively administering the insecticides with possible resistance and low resistance. Additionally， we should continue to monitor the resistance and guide the rational use of insecticides.

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ² = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ² = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.
Infant ; Female ; Male ; Humans ; Child ; Infant, Newborn ; Child, Preschool ; DNA Copy Number Variations ; Drug Resistant Epilepsy/genetics* ; Retrospective Studies ; Polymorphism, Single Nucleotide

Objective:To investigate the risk factors of in-hospital mortality in elderly patients with traumatic brain injury (TBI).Methods:A case control study was conducted on 709 elderly patients with TBI admitted to Luhe Hospital, Capital Medical University from January 2012 to October 2018, including 468 males and 241 females; aged 60-97 years [(70.4±8.5)years]. Patients were divided into death group ( n=82) and survival group ( n=627) based on death or not during hospitalization. Data of the two groups were documented, including gender, age, causes of injury (traffic accident injury, fall injury, assault injury or others), history of comorbidities (hypertension, coronary heart disease, diabetes or coronary heart disease), Glasgow coma score (GCS) on admission, operation modalities (trepanation and drainage, hematoma evacuation, decompressive craniectomy or intracranial pressure monitoring), complications (pneumonia, stress ulcer, electrolyte imbalance, hypoproteinemia or secondary epilepsy) and length of hospitalization. Univariate analysis was used to analyze the correlation between the above factors and in-hospital mortality in elderly patients with TBI. Multivariate Logistic regression analysis was used to determine the independent risk factors for their in-hospital mortality. Results:Univariate analysis showed that sex, causes of injury, hypertension, cerebral infarction, diabetes, GCS on admission, hematoma evacuation, decompressive craniectomy, intracranial pressure monitoring, pneumonia, stress ulcer and length of hospital stay were correlated with in-hospital mortality in elderly patients with TBI ( P<0.05 or 0.01), while there was no correlation with age, history of coronary heart disease, trepanation and drainage, electrolyte imbalance, hypoproteinemia and secondary epilepsy (all P>0.05). Multivariate Logistic regression analysis showed that fall injury ( OR=0.28, 95% CI 0.08-0.96, P<0.05), hypertension ( OR=0.29, 95% CI 0.10-0.84, P<0.05),GCS of 9-12 points on admission ( OR=12.98, 95% CI 4.70-35.84, P<0.01), GCS of 3-8 points on admission ( OR=33.67, 95% CI 14.01-80.93, P<0.01) and length of hospital stay<11 days ( OR=0.06, 95% CI 0.02-0.13, P<0.01) were significantly associated with their in-hospital mortality. Conclusions:Fall injury, hypertension, GCS≤12 points on admission and length of hospital stay <11 days are independent risk factors for in-hospital mortality in elderly patients with TBI, especially that patients with GCS of 3-8 points on admission have higher in-hospital modality than patients with GCS≥ 9 points, indicating the importance of above independent risk factors in evaluating outcome.

Objective:To correlate creatine kinase (CK) and creatine kinase- isoenzyme MB (CK-MB) with different states of bipolar disorder in patients.Methods:A total of 206 patients with bipolar disorder who received treatment in The 7 th People's Hospital of Wenzhou, China between January 2018 and June 2019 were included in the patient group. A total of 369 healthy controls who concurrently received physical examination were included in the control group. CK and CK-MB levels were detected in all participants. The Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAMD)-7 scale, the Bech-Rafaelsen Melancholy Scale (BRMS), and modified version of the Overt Aggression Scale (MOAS) were used to evaluate the mental symptoms, depression, mania and aggression of patients. The CK and CK-MB levels were compared between patients with different states of bipolar disorder. Results:In the control group, CK and CK-MB levels in males were 112.5 (94.5, 156.5) U/L and 17.0 (15.0, 20.0) U/L, respectively, which were significantly higher than those in females [73.0 (61.0, 86.3) U/L, 15.0 (13.0, 18.0) U/L, Z = -9.732, -3.535, both P < 0.001). In the patient group, CK and CK-MB levels in males were 129.0 (80.0, 233.5) U/L, 12.0 (10.0, 17.0) U/L, respectively, which were significantly higher than those in females [73.0 (55.0, 94.0) U/L, 13.5 (11.0, 17.0) U/L, Z = -9.510, -4.746, both P < 0.001]. There was no significant difference in CK level in males between the control and patient groups ( Z = -1.003, P = 0.316), but significant difference in CK-MB level in males was observed between the two groups ( Z = -6.570, P < 0.001). There were significant differences in CK and CK-MB levels in females between the control and patient groups ( Z = -2.535, -9.707, P = 0.011, P < 0.001). In the patient group, CK level in the manic, depressive, and symptom-alleviated states was 132.0 (78.0, 297.0) U/L, 85.0 (56.0, 145.0) U/L, 128.0 (110.0, 165.0) U/L respectively in males, and it was 73.0 (49.0, 122.3) U/L, 51.0 (45.0, 67.0) U/L and 84.5 (61.0, 193.0) U/L, respectively in females. There was significant difference in CK level in males and females between different states of bipolar disorder ( χ2 = 9.019, 16.720, P = 0.011, P < 0.001). In males, CK level was correlated with the BPRS total score, BRMS total score, and MOAS total score in the manic state, as well as the BPRS total score in the symptom-alleviated state ( r = 0.282, 0.286, 0.236, 0.574). In females, CK level was correlated with the MOAS total score in the manic state ( r = 0.260). In males, CK-MB level was correlated with the BRMS total score in the manic and depressive states ( r = 0.186 and 0.496). In females, CK-MB level was correlated with the MOAS total score and the BRMS total score in the manic state ( r = 0.155, 0.572). Conclusion:CK and CK-MB levels are correlated with bipolar disorder in different states and they are of certain clinical significance and provide innovative insights into the diagnosis of bipolar disorder.

OBJECTIVE: To analyze the phenotype and genetic variant in a pedigree affected with inherited protein C (PC) deficiency. METHODS: The proband and her family members (7 individuals from 3 generations) were tested for plasma protein C activity (PC:A), protein C antigen (PC:Ag) content and other coagulation indicators. All of the 9 exons and flanking sequences of the proband's PROC gene were amplified by PCR and sequenced. Suspected variants were verified by reverse sequencing of the proband and her family members. Bioinformatic software was used to analyze the pathogenicity and conservation of the variant site. Swiss-PdbViewer was used to analyze the three-dimensional model and the interaction with the mutant amino acid. RESULTS: The PC:A and PC:Ag of the proband, her grandmother, father and elder brother were decreased to 55%, 52%, 48%, 51% and 53%, 55%, 50%, 56%, respectively. Genetic analysis showed that the four individuals have all carried heterozygous c.1318C>T (p.Arg398Cys) missense mutation in exon 9 of the PROC gene. The score of MutationTaster was 0.991, PROVEAN was -3.72, and FATHMM was -2.49, all predicted it to be a harmful mutation. Phylogenetic analysis also showed that Arg398 was weakly conservative among homologous species. Protein model analysis showed that, in the wild type, Arg398 can form a hydrogen bond with Glu341 and Lys395 respectively, when it was mutated to Cys398, the hydrogen bond with Glu341 disappears and an additional hydrogen bond was formed with Lys395, which has changed the spatial structure of the protein. CONCLUSION The heterozygous missense mutation c.1318C>T (p.Arg398Cys) of the PROC gene probably underlay the decreased PC:A and PC:Ag in this pedigree.
Aged ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Phylogeny ; Protein C Deficiency/genetics*

Objective:To investigate the characteristics and management of the emergency patients with orthopaedic trauma during COVID-19 epidemic.Methods:A retrospective analysis was performed of the 32 emergency inpatients at Department of Orthopedics, Nanfang Hospital from January 20 to February 26, 2020. They were 23 males and 9 females, aged from 4 to 66 years (mean, 35 years). The causes for their injury included traffic accident in 14 cases, sharp cutting (e.g. by a kitchen knife) in 6 cases, heavy object crushing in one, machine crushing in one, fall in 2, and machine twisting in one. High energy injury occurred in 13 cases and low-energy injury in 9 cases. The injury involved the upper limb in 7 cases and the lower limb in 15 cases. Grade Ⅱ protection was adopted during the diagnosis and treatment for the one emergency patient who had not undergone nucleic acid screening for 2019-nCoV while grade Ⅰ protection for the other 21 patients. 2019-nCoV infection was recorded in the patients and medical staff as well. The measures and experience were reviewed in the management of orthopaedic emergencies during the COVID-19 epidemic.Results:During the diagnosis and treatment of 22 emergency patients with orthopaedic trauma, none of the medical staff or patients was infected with COVID-19. As the one emergency patient was treated as a suspected case and protected by grade Ⅱ measures, COVID-19 infection was ruled out after surgery.Conclusions:During the COVID-19 epidemic, front-line medical staff dealing with traumatic emergencies faced a higher risk of infection. The emergency orthopaedic traumas were mainly caused by a traffic accident or a machine, and those in the elderly patients by a sharp cutting or a fall. The incidence of COVID-19 infection could be reduced by COVID-19 screening before admission, appropriate anesthesia and surgical methods, protection of perioperative medical staff, postoperative wards care and psychological counseling.

Objective To examine the effects of participating in Balint group ( PBG) for reducing occupational burnout among primary care physicians (PCPs). Methods In this randomized controlled trial, 240 PCPs were randomly assigned to PBG (n=70) and control group (n=240) in propotion of 1 ∶ 2. Sub-jects of PBG received Balint group intervention for one year,while control group received natural observation. Maslach Burnout Inventory ( MBI) was used to assess the severity of occupational burnout. Results At baseline all three subscales of MBI had no significant difference between PBG and cotrol group(P>0. 05). After the intervention,PBG had statistically lower subscale scores in emotional exhaustion ((20. 1±8. 3) vs (22. 6±8. 7),t=1. 993,P=0. 048) and depersonalization (( 6. 8± 4. 9) vs ( 10. 8 ± 5. 2),t=5. 355,P<0. 001) than the control group, while had statistically higher score in personal accomplishment subscale ((38. 3±7. 5) vs (34. 6±7. 7),t=3. 311,P=0. 001) than the control group. Conclusions PBG is effective in reducing occupational burnout among PCPs.