[Chronic myeloid leukemia with e6a2 fusion gene: a case report and literature review].

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

[Preliminary study on implementation of modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy].

Objective: To investigate the feasibility and safety of implementing modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy. Methods: In this retrospective, descriptive case series, we analyzed clinical data of seven patients who had undergone laparoscopic proximal gastrectomy and gastrointestinal reconstruction with modified tubular gastric side-overlap anastomosis from October 2022 to March 2023 in the Second Affiliated Hospital of Fujian Medical University. The study patients comprised five men and two women aged 57-72 years and of body mass index 18.5-25.7 kg/m2. All seven patients had preoperative gastroscopic and pathological evidence of esophagogastric junction cancer and all were found by preoperative enhanced computed tomography and/or endoscopic ultrasonography to have stage CT1-2N0M0 tumors. The main steps in the reconstruction of a modified tubular gastric side-overlap anastomosis are as follows: (1) mobilizing the lower esophagus and opening the left pleura to expand the space; (2) severing the esophagus with a linear cutter stapler; (3) creating a 3-cm-wide tubular stomach along the greater curvature; (4) creating a 5-cm guide line on the lesser curvature of the anterior wall of the tubular stomach and a small opening below the guide line; (5) rotating the esophageal stump 90° counterclockwise and making a small opening on the right posterior wall of the esophageal stump, along with using a 45-mm linear cutter stapler for esophagogastric side-to-side anastomosis under the guidance of the gastric tube and guide line ; (6) closing the common opening using barbed sutures; (7) embedding the cut edge of the esophageal stump such as to closely oppose it to the esophagus; (8) using barbed sutures to continuously suture the lower esophagus bilaterally to the anterior wall of the tubular stomach; and (9) closing the opened esophageal hiatus and pleura. The main outcome measures were intraoperative (operation time, digestive tract reconstruction time, closing the common opening time, intraoperative blood loss, and number of dissected lymph nodes), postoperative (time to passage of flatus , time to liquid diet, time to ambulation, length of postoperative hospital stay, and postoperative complications), pathological (maximum diameter of the tumor and pathological stage) and findings on follow-up. Results: Laparoscopic proximal gastrectomy with reconstruction of a modified tubular gastric side-overlap anastomosis was successfully completed in all seven patients; no conversion to laparotomy was required and there were no postoperative complications. The operation time, digestive tract reconstruction time, and closing of common opening time were 187-229, 61-79, and 7-9 minutes, respectively. Intraoperative blood loss was 15-23 ml and the number of dissected lymph nodes was 14-46 per case. Time to passage of flatus, time to liquid diet, time to ambulation, and postoperative hospital stay were 1-2, 2-3, 3-4, and 6-7 days, respectively. Postoperative pathological examination showed that the maximum tumor diameters were 1.6-3.3 cm in four patients with stage IA disease and three patients with stage IB. The seven patients were followed up for 6-11 months, during which none required routine use of proton pump inhibitors or gastric mucosal protective agents and there were no deaths or tumor recurrence/metastasis. No patients had anemia or hypoproteinemia 3 and 6 months after surgery. Six months after surgery, NRS2002 and GERDQ scores were 1-2 and 2-3, respectively. Gastroscopy showed narrow anastomoses in 6 patients with Los Angeles grade A and one patient with grade B disease. No evidence of significant bile reflux was found and no anastomotic stenosis or reflux was detected on upper gastrointestinal angiography. Conclusion: It is safe and feasible to implement modified tubular gastric side-overlap anastomosis for digestive tract reconstruction in laparoscopic proximal gastrectomy.

[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

A comprehensive analysis of nucleotide excision repair characteristics defines a novel prognostic signature for acute myeloid leukemia.

OBJECTIVE: Nucleotide excision repair (NER) has been associated with various types of malignant tumors. However, the precise roles of nucleotide excision repair-related genes (NERGs) in acute myeloid leukemia (AML) remain incompletely understood. Hence, this study aimed to develop a prognostic signature incorporating NERGs in AML, which could potentially predict patient outcomes. MATERIALS AND METHODS: By querying the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases, we acquired RNA-seq data and clinical information pertaining to AML. To identify differentially expressed NERGs (DE-NERGs), we employed the Wilcoxon rank-sum test. Based on the expression patterns of DE-NERGs with prognostic significance, patients were categorized into two subgroups. A prognostic signature was developed through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to compare the differentially expressed genes (DEGs) between these two groups. Additionally, a nomogram was constructed using multivariate analysis. The biological pathways involved were elucidated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). RESULTS: We developed a prognostic model based on an 11-gene signature. Furthermore, the risk score derived from this model was demonstrated to independently serve as a prognostic marker for patients diagnosed with AML. CONCLUSIONS: Our prognostic model, based on NERGs, was developed and validated to provide insights into the onset and progression of AML and establish a foundation for more effective treatment. Our findings not only contribute to clinical decision-making but also underscore the significance of nucleotide excision repair. Furthermore, they may pave the way for the development of targeted therapeutic strategies specifically focused on this process.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases].

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.

[Examining fermented mustard brine in terms of traditional Chinese medicine].

Fermented mustard brine was a unique liquid fermented with mustard long used in traditional Chinese medicine. It was previously known as Ji Shui, which refered to the yellow salty water after vegetables were fermented. Fermented mustard brine was not established in TCM until the Ming Dynasty. It was found that the original plant of ancient mustard was Brassica juncea (L.) Czern et Coss. var. juncea, and the origin of the mustard used in mustard brine mainly refereed to the cultivated species of Brassica (Brassica juncea var. multiceps Tsen et Lee) in the Brassica branch of the Cruciferae family, which belonged to the mustard leaf class in tillering mustard. Fermented mustard brine tasted spicy and salty and was considered as a feature of cold, and went to the lung meridian. Its effects were of clearing heat and reducing phlegm, calming coughing and expelling pus. It was mainly used for the treatment of lung carbuncle, and also for diseases such as lung impotence, laryngeal tinea, wheezing, coughing, vomiting pus and blood, and facial swelling. The ways to use it involved taking it directly (or taking it warm), taking it with hot soybean milk, having it with food, mixing it with decoction, and mixing it with houttuynia cordata juice. It was mainly produced in the Jiaxing area of Zhejiang province, especially famous for the collection by the Tianning Temple in Tianning in Jiashan, not the Tianning Temple in Changzhou.

[Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations].

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

[Pulmonary granular cell tumors: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.

Hysterectomy and risk of osteoarthritis in women: a nationwide nested case-control study.

OBJECTIVE: Hysterectomy is the most common gynaecological surgery, performed mainly for benign uterine pathologies in women. Studies have suggested that hysterectomy is associated with osteoarthritis (OA); however, the association remains controversial. This study aimed to investigate the association between hysterectomy and the risk of OA. METHOD: We performed a population-based nested case-control study using the National Health Insurance programme database from 2000 to 2016 in Taiwan. All medical conditions for each case and control were categorized using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10. A multiple conditional logistic regression model was applied to analyse the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between hysterectomy and OA. RESULTS: Our analyses included 16 592 patients with OA and 66 368 matched controls. After adjustment for possible confounders, hysterectomy had a significant association with OA (aOR = 1.19, 95% CI = 1.09-1.30), especially knee OA (aOR = 1.25, 95% CI = 1.13-1.38). Furthermore, women who received oestrogen therapy (ET) alone and patients who underwent hysterectomy without ET showed a greater risk of OA development compared to women who did not receive ET (aOR = 1.14, 95% CI = 1.07-1.23, and aOR = 1.19, 95% CI = 1.08-1.31, respectively). CONCLUSION: Our findings indicate that hysterectomy is associated with OA, especially knee OA. We also found that women who received ET alone and patients who underwent hysterectomy without ET had an increased risk of OA.