Objective:To determine the clinical factors affecting Central lymph node metastases (CLNM) of single Papillary thyroid carcinoma (PTC). To predict the value of age for CLNM under different genders and the status of Hashimoto’s thyroiditis (HT) .Methods:The clinical data of 4 115 patients with PTMC (≤10.0 mm) and 664 patients with PTC (> 10.0 mm) in Hangzhou First People’s Hospital affiliated to Westlake University Medical School from Jan. 2010 to Aug. 2023 were retrospectively analyzed, and the independent risk factors of PTMC and PTC CLNM were identified by univariate and multivariate logistic regression analysis. According to different gender and HT status, the patients were divided into male group, female group, HT group and non-HT group. The optimal age threshold and diagnostic efficacy of CLNM in each subgroup were determined by Receiver operating characteristic area under the curve (AUC) .Results:The proportion of CLNM in 3451 PTMCs and 664 PTCs was 27.2% (937/3451) and 58.9% (391/664) ( χ2=256.565, P<0.050), respectively. Univariate and multivariate regression analysis showed that larger tumor ( OR 1.230), male ( OR 2.085), older age ( OR 0.960) and HT ( OR 0.697) were independent predictors of the occurrence of CLNM in PTMC. Only male ( OR 1.460) and older ( OR 0.963) PTC were independently associated with CLNM. Subgroup analysis showed that the age-predicted AUC of CLNM in male, HT and non-HT patients in PTC were higher than that of PTMC, which were 0.642-0.689 and 0.635-0.659, respectively. The age thresholds of female, HT and non-HT subgroups in PTC were lower than those in PTMC, which were 38.5 to 39.5 years old and 41.5 to 42.5 years old, respectively. Conclusions:Larger tumor, male, older patients and HT can independently predict the risk of CLNM in PTMC, while only male and older people can independently predict the risk of CLNM in PTC. There are certain differences in the age of CLNM occurrence between PTMC and PTC patients with different genders and HT combination status. It is of great significance to correctly understand these differences for providing personalized clinical treatment.

Objective To establish an optimal limiting dose for dose limiting rings placed in the anterior and posterior regions of the neck for reducing head and neck lymphedema under intensity-modulated radiation therapy(IMRT)for early nasopharyngeal carcinoma(NPC)from a dosimetric perspective.Method Fifteen newly diagnosed early-stage nasopharyngeal carcinoma patients who underwent CT localization for radiotherapy at the Cancer Hospital of Guangzhou Medical University from January to September 2022 were included in the study.Each case was designed with five sets of radiotherapy plans.Plan A consisted of conventional unlimited-field plans,while Plans B-E consisted of limited-field plans with dose constraints set at 20,18,16,and 14 Gy,respectively,with the remaining parameters consistent with Plan A.The impact on target coverage and organ-at-risk constraints was evaluated through variance analysis and pairwise multiple comparisons using a randomized block design to determine the optimal dose limits.Results The gradient of 16Gy was determined as the optimal dose limiting cutoff point for achieving the balance between target coverage and organ limiting dose.Compared with the conventional plan,The plans with the placement of a cervical anterior and posterior dose limiting ring(16Gy)did not change the target dose coverage(P>0.05),but only yielded a slight change in the homogeneity index(P<0.05).It did not cause any changes of the dosage in the inner ear,mandible,and brainstem(all P>0.05),but lead to statisti-cally significant reductions in the oral cavity,throat,and thyroid(all P<0.05).It caused a slight increase of the dose in the parotid gland and spinal cord(both P<0.05),but the increased dose was anyhow within the tolerance range.Conclusion The dosimetric investigation determines an optimal dose limit cutoff point for the cervical ante-rior and posterior dose limiting rings.It is expected to provide a design method for IMRT plans to reduce head and neck lymphedema after radiotherapy for early NPC.

Objective Based on the multi-software visual analysis of the literature on the effect of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway on rheumatoid arthritis in the past decade,the development trend and research hotspot in this field are summarized.To provide researchers with new directions and ideas to promote the innovative development of the field.Methods The literatures related to JAK/STAT signaling pathway in rheumatoid arthritis were collected from the Web of Science Core Collection database from 2013 to 2023.CiteSpace and VOSviewer software were used to analyze the number of publications,countries,authors and keywords of 354 articles retrieved.Results The number of published papers in this field continues to increase.According to the author's research direction,the presentation of high-frequency words,and the attention to the preface and hot topics,it is suggested that this field focuses on gene expression,immune mechanism,inflammatory mechanism,pathway inhibitors,drug therapy,etc.Future research will focus on the safety,mechanism and controlled trials of pathway inhibitors and antirheumatic drugs.Conclusion The effect of JAK/STAT signaling pathway on rheumatoid arthritis has attracted much attention in the past,present and future.There are differences in the research of different teams in this field,and the regional development is unbalanced,suggesting that we should strengthen cooperation and exchanges,focus on the international frontier,and carry out more high-quality research to promote the development and progress of this field,and provide clinical basis.

Objective:To investigate the effect of alanine aminotransferase(ALT) level in early pregnancy and its interaction with maternal body mass index(BMI) on neonatal birth weight.Methods:Data of full-term singleton delivery mother-infant pairs from 2014 to 2016 in Wenzhou were collected. The exposure(ALT>40 U/L) and non-exposure(ALT≤40 U/L) groups were matched using 1∶4 propensity score matching. Logistic regression analysis was used to analyze the relationship between increased ALT level in the first trimester and abnormal birth weight as well as the effect of its interaction with BMI on abnormal birth weight.Results:Multivariate analysis showed that the risks of macrosomia and large for gestational age(LGA) in pregnant women with ALT>40 U/L were 1.584(95% CI 1.323-1.896) and 1.292(95% CI 1.142-1.461) compared with those with ALT≤40 U/L. ALT in the first trimester displayed an additive interaction with BMI on the risk of macrosomia [the relative excess risk due to interaction( RERI)=2.032, 95% CI 0.307-3.757, the attributable proportion due to interaction( API)=0.448, 95% CI 0.221-0.684, the synergy index( S)=2.348, 95% CI 1.274-4.324]. In addition, there was no interaction between ALT and BMI on the risk of LGA, and nor did the association of ALT in the first trimester with low birth weight or small for gestational age exist. Conclusion:ALT>40 U/L in the first trimester increases the risk of high birth weight, especially in overweight or obese pregnant women in the first trimester. Therefore, it is suggested to strengthen the monitoring of ALT level in obese pregnant women during the first trimester.

As an important branch of artificial intelligence, machine learning is widely used in various fields. Machine learning has similarity to classical statistical methods, but can solve many problems which are difficult for traditional statistics, so it is one of the important tools in epidemiological research. This paper introduced 9 common algorithms of machine learning and summarized their characteristics and applications in epidemiological research. Readers could choose appropriate machine learning method according to the research purpose for the better application of machine learning in epidemiological research.

Objective:To compare the incidence of radiation pneumonitis (RP) between lung cancer patients from the European, American and Asian regions.Methods:The studies related to lung cancer and RP were searched from PubMed, Embase, and Cochrane library. According to the different places where the studies were conducted, the searched studies were divided into two types: Asian studies and European, American and Australian studies. The incidence of RP between two regions was summarized. Studies related to dosimetry parameters were searched from PubMed database.Results:A total of 3, 190 patients from 14studies were included. Meta-analysis results showed that the incidence of ≥ grade 3 RP was similar in patients from Asia and Europe, America and Australia (4.9% vs. 4.6%, P=0.895), whereas the incidence of grade 5 RP in Asia was significantly higher than that in Europe, America and Australia (1.5% vs. 0.2%, P=0.002). Moreover, the lung irradiation dose received by the patients in the Asian group was relatively low. Lung V 20Gy dose limitation standard was reported in 21studies. Further analysis found no statistical significance in lung V 20Gy dose limitation standard between two regions ( P=0.440), and the standard in Asian studies is likely to be even stricter. Conclusions:The incidence of RP after chemoradiotherapy in lung cancer patients in Asia is relatively higher compared with those in Europe, America and Australia. The differences in dose limitation standard should be noted when the thoracic radiation regimen based solely on the data from foreign studies is applied to the patients in Asia.

Objective:To analyze the influence of CD19 isoforms to the efficacy of CD19/CD3 Bispecific T-cell Engager (BiTE) antibody, and explore the resistance mechanism of BiTE immunotherapy.Methods:Semi-quantitative RT-PCR (qRT-PCR) was used to detect the expression of CD19 mRNA isoforms before and after BiTE treatment in a patient with CD19 + B cell acute lymphoblastic leukemia (ALL) . CD19 isoforms were analyzed by Sanger sequencing. Flow cytometry and transcriptome sequencing were performed to analyze the expression of cell lineage specific molecules before and after BiTE treatment. Results:The expression of CD19 isoform with exon 2 deletion was identified at diagnosis. After relapsed and treatment of BiTE antibody, the patient did not achieve remission and CD19 antigen on leukemic cells turned negative detected by flow cytometry after BiTE treatment. However the expression ratio of CD19 isoform with exon 2 deletion was not increased. Flow cytometry phenotype and transcriptome sequencing confirmed that no linage switching developed, which suggested the expression of CD19 isoform caused by exon alternative splicing and lineage switching was not related to CD19 epitope loss in this patient. This patient achieved complete remission by sequential administration of self-developed CD22 CAR-T and CD19 CAR-T after disease progression.Conclusion:Targeting or combining an alternative antigen specific CAR-T may be a promising treatment option after losing CD19 expression in relapsed ALL.

Objective: To evaluate the significance of double pancreatico-jejunostomy in preventing pancreatic fistula after central pancreatectomy (CP) . Methods: The clinical data of 10 patients who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from Feb. 2012 to Dec. 2018 were analyzed retrospectively. Results: All the 10 patients underwent CP, closure of the proximal pancreatic stump, and end-to-side invaginated pancreaticojejunostomy; At the same time, invaginated pancreaticojejunal anastomosis or duct-to-mucosa pancreaticojejunostomy was performed to the distal pancreatic remnant. The duration of the operation was (240±60) min, and the average intraoperative blood loss was 300 ml. Incidence of pancreatic fistulas was 30% (3/10) . There were no grade B or C pancreatic fistulas, or perioperative deaths. The duration of postoperative hospital stay varied from 9 to 25 days. Endocrine and exocrine functions were well maintained during the follow-ups of 7 months to 5 years, and no tumors recurred. Conclusions Although operation time and technical difficulty increase, central pancreatectomy using double pancreaticojejunostomy is safe, feasible, and appears to be associated with a low rate of postoperative pancreatic fistulas.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Objective To explore changes of levels of interferon‐γ(IFN‐γ) ,interleukin‐32(IL‐32) and interleukin‐6(IL‐6) in pe‐ripheral blood and the correlation between peripheral IFN‐γ,IL‐32 ,IL‐6 and liver function level and hepatitis B virus(HBV) DNA load in HBV carriers .Methods Sixty HBV carriers ,including 39 cases of chronic HBV carriers and 21 cases of inactive hepatitis B surface antigen(HBsAg) carriers ,and 50 healthy individuals were collected .Serum levels of IFN‐γ,IL‐32 and IL‐6 ,the amount of HBV DNA and liver function were detected ,and clinical correlations were analysed .Results Compared with the control group ,ser‐um levels of IFN‐γ,IL‐32 and IL‐6 of chronic HBV carriers and inactive HBsAg carriers were significantly increased (P<0 .05) . Compared with chronic HBV carriers with low amount of HBV DNA loads and high amount of HBV DNA loads ,chronic HBV car‐riers with medial HBV DNA loads had higher serum levels of IFN‐γ,IL‐32 and IL‐6 ,but no statistically significant differences were observed(P>0 .05) .There was positive correlation between IL‐32 level and ALT level (r=0 .32 ,P<0 .05) ,and negative correla‐tion between IL‐32 level and ALB level(r= -0 .27 ,P<0 .05) .Conclusion IFN‐γ,IL‐32 and IL‐6 may play important roles in chro‐nic HBV infection ,the levels of IFN‐γ,IL‐32 and IL‐6 could be used as important indicators to assess the severity of inflammation in HBV carriers .