[Correlations between the average Young's modulus and histopathological characteristics of papillary thyroid carcinoma].

Objective: To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC). Methods: Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean. Results: The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean (r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean (r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without (P=0.014). There were statistical differences in the Emeans among different types of pathological calcification (P＜0.001). The multiple linear regression analysis showed that the lesion size (ß=0.325, P＜0.001), degree of fibrosis (ß=0.563, P＜0.001), psammoma bodies (ß=0.177, P=0.001), stromal calcification (ß=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma (ß=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions: The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

[Clinical characteristics of posterior malleolus fracture in adults].

Objective: To explore the latest clinical characteristics and development trends of posterior malleolus fracture. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to December 2022 were reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture with a mean age of (48.7±15.6) years were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59 years. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). The number of cases according to different fracture types showed the following descending order: trimalleolar fracture-supination extorsion (335 cases, 71.0%), bimalleolar fracture (60 cases, 12.7%), trimalleolar fracture-pronation extorsion (43 cases, 9.1%), posterior malleolus+tibial shaft fracture (19 cases, 4.0%), simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi Ⅰ, Ⅱ and Ⅲ type of posterior malleolus fractures was 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji ⅡA type represented the highest number of cases (249 cases, 52.8%), followed by the ⅡB type (120 cases, 25.4%), Ⅰ type (54 cases, 11.4%), ⅢB type (36 cases, 7.6%), and ⅢA type (13 cases, 2.8%). However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions from the year of 2014 to 2022 (all P>0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination extorsion, Haraguchi Ⅰ type and Tongji ⅡA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59 years. There has been no significant change in the development trend of clinical characteristics of posterior malleolus fractures in recent years.

[Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model].

Objective: To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. Methods: PV patients with JAK2V617F gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age M (Q1, Q3) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [M (Q1, Q3)] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Results: Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all P<0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all P<0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (P=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (P<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (HR=2.031, 95%CI: 1.297-3.179, P=0.002), V617F%≥50% (HR=2.141, 95%CI: 1.370-3.347, P=0.001), ASXL1 mutation (HR=4.632, 95%CI: 1.497-14.336, P=0.008), spleen subcostal≥5 cm (HR=1.771, 95%CI: 1.047-2.996, P=0.033) are the risk factors of venous thrombosis in PV patients. According to HR values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95%CI: 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Conclusions: Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

[Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers].

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

[Correlation between BRAFV600E mutation and aggressive biological behavior of papillary thyroid carcinoma].

The current study analyzed the mutation rate of BRAFV600E in papillary thyroid carcinoma patients and the correlation between BRAFV600E mutation and aggressive biological behavior of papillary thyroid carcinoma. A total of 160 patients with papillary thyroid carcinoma who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from October 2020 to November 2021 were retrospectively included. All patients underwent BRAFV600E gene detection. There were 37 males and 123 females, with a mean age of (46.5±11.1) years. The mutation rate of BRAFV600E was 86.3% (138/160). There was no significant correlation between the mutation of BRAFV600E and aggressive factors such as age (P=0.917), single focal/multifocal tumor (P=0.673), tumor size (P=0.360), tumor invasion (P=0.150) and regional lymph node metastasis (P=0.406). Therefore, for papillary thyroid cancer, mutations in a single gene like BRAFV600E fail to determine more active diagnosis and treatment.

[Efficacy of Hintermann calcaneal lengthening osteotomy for flexible flatfoot].

Objective: To investigate the clinical efficacy of Hintermann osteotomy (H-LCL) for flexible flatfoot. Methods: A follow-up study. Clinical data of 30 patients with flexible flatfoot treated with H-LCL operation from January 2020 to December 2021 in Sports Medical Center of the First Affiliated Hospital of Army Medical University were retrospectively analyzed. There were 8 males and 22 females, with a mean age of (39.0±15.2) years. The mean time from symptom onset to the diagnosisï¼»M（Q1，Q3）］was 24.0 (5.5, 102.0) months. The functional and imaging scores of the patients before and after the last follow-up were compared to evaluate the clinical efficacy of the operation. The functional scores included American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) of pain, pain interference (PI) and physical function (PF) index in Patient-Reported Outcomes Measurement Information System (PROMIS). And the imaging scores included Meary's angle, calcaneal pitch angle, calcaneal valgus angle and talonavicular coverage angle. Results: The mean operation time was (82.3±24.4) min, and the follow-up periods was (17.9±6.9) months. At the last follow-up, VAS of pain [M(Q1, Q3)] decreased from 5 (4, 6) to 2 (1, 2); PI decreased from 59.8±5.0 to 44.6±5.7; AOFAS increased from 65.2±10.0 to 85.8±3.3; PF increased from 50 (48.5,51.0) to 58.5 (54.0, 66.0); Meary's angle (antero-posterior image) decreased from 15.7° (10.1°, 29.2°) to 3.9° (2.6°, 5.3°); Meary's angle (lateral image) decreased from 13.5°±6.8° to 4.4°±2.6°; calcaneal pitch angle increased from 14.0°±3.3° to 18.6°±4.2°; calcaneal valgus angle decreased from 12.6°±7.3° to 4.3°±2.5°; and talonavicular coverage angle decreased from 20.9°±10.7° to 7.7°±5.2°. The up-mentioned parameters were all improved statistically significant at the last follow-up when compared with those before the operation (all P<0.05). Conclusion: H-LCL brings a significant improvement of clinical outcome scores and good radiological correction of flatfoot deformities in correcting flexible flatfoot, it conforms to the anatomical characteristics of the subtalar joint.

[Clinical features of IgG4-related lung disease].

Objective: To explore the clinical features of IgG4-related lung disease. Methods: The clinical data of 60 patients diagnosed with IgG4-related lung disease in Peking University People's Hospital from February 2012 to May 2021 were retrospectively collected. Analysis was made to explore the features of clinical manifestation, laboratory, imaging, prognosis and other characteristics of the disease. Results: A total of 60 patients were included, with 40 males, age of (58.2±12.9) years, an age of onset of (57.1±13.2) years, and 31.7% (19 cases) of the patients had a history of allergic disease. 36.7% (22 cases) of the patients had respiratory symptoms during the disease. 94.6% (53/56) of patients had serum IgG4>1.35 g/L, 24.1% (14/58) of patients had increased eosinophils, 79.2% (38/48) of patients had increased IgE level, and 53.7% (29/54) of patients had decreased C3 or C4. Common imaging findings included nodular changes (38 cases, 63.3%), mediastinal and/or hilar lymphadenopathy (34 cases, 56.7%), and ground glass opacities (31 cases, 51.7%). Fifty-three cases (88.3%) showed two or more imaging changes. The pathological examination of the patient was mainly characterized by lymphoplasmacytic infiltration and fibrosis, with only one case of phlebitis obliterans. Compared with the asymptomatic group (38 cases), patients with respiratory symptoms (22 cases) showed higher level of serum total IgG and eosinophils (43.2 vs 17.8 g/L, 0.30×109/L vs 0.14×109/L, P<0.05), lower proportion of allergic diseases, and higher proportion of consolidation shadows on chest CT (P<0.05). There were no significant differences in serum IgG4, IgE, complement levels, and imaging outcomes after treatment between the two groups (P>0.05). Conclusions: The clinical manifestations of IgG4-related lung disease are atypical, and asymptomatic patients account for a high proportion. The imaging of the disease is highly heterogeneous, and patients are prone to show coexisted multiple imaging changes. The main clinical features and imaging outcomes of patients with and without respiratory symptoms are not significantly different.

[Clinical and laboratory features of SF3B1-mutated myeloproliferative neoplasms].

Objective: To explore the clinical and laboratory characteristics of SF3B1 gene mutations in myeloproliferative neoplasms (MPN) patients. Methods: The clinical data of 273 MPN patients who were diagnosed MPN and treated in the Second Hospital of Tianjin Medical University from November 2017 to March 2023 were retrospectively analyzed. There were 133 males and 140 females, with a median age M(Q1,Q3)of 56(46, 67) years. The molecular biology and cytogenetic characteristics were detected by second-generation sequencing (NGS) and R+G banding techniques, and the clinical and laboratory characteristics of patients with SF3B1 gene mutation were analyzed. Results: SF3B1 gene mutations were found in 13 patients (4.8%, 13/273).The types of SF3B1 mutations included missense (92.3%, 12/13) and nonsense mutations (7.7%, 1/13).Compared to the non-mutant cohort, patients in SF3B1 mutant cohort had older ages [68(51, 76) vs 56(45, 66)years,P=0.025], higher proportion of splenomegaly [46.2%(6/13) vs 15.8%(41/259),P=0.014]and secondary tumor [23.1%(3/13)vs 3.8%(10/260), P=0.018]with higher proportion of bone marrow blast [0.5%(0, 1.5%) vs 0(0, 0.5%),P=0.002] and lower hemoglobin[(104±36) vs (137±40) g/L,P=0.004] and hematocrit [31%(22%, 40%) vs 41%(35%, 52%),P=0.003]. All of the 10 patients in the SF3B1 mutant cohort whose ring sideroblast (RS) could be evaluated showed no RS formation. The overall survival, thrombosis-free survival and leukemia free survival of MPN patients in SF3B1 mutant cohort were 4.0 (2.0, 6.0), 2.0 (0.5, 4.5) and 4.0 (2.0, 6.0) years, respectively, while patients in the non-mutant cohort were 6.0 (3.0, 10.0), 5.0 (1.0, 8.0), 6.0 (3.0, 10.0) years, respectively, there were no statistical significance between two groups (Z=3.69, 1.66, 2.05, all P>0.05).The secondary tumor free survival of SF3B1 mutant cohort patients was 4.0 (2.0, 6.0) years, which was lower than that of non-mutant cohort patients [5.5 (3.0, 10.0) years, Z=18.18, P<0.001). Conclusions: MPN patients with SF3B1 gene mutations are older, more prone to splenomegaly and secondary tumors. They also have a higher proportion of bone marrow blast, lower hemoglobin and hematocrit, and show no RS formation.

[Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm].

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-ß in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

[Analysis of risk factors for thromboembolism in patients with JAK2V617F gene mutation positive myeloproliferative neoplasms].

Objective: To analyze the risk factors of thrombosis in patients with JAK2V617F mutation positive myeloproliferative neoplasms (MPN). Methods: A total of 223 MPN patients with JAK2V617F mutation in the Second Hospital of Tianjin Medical University from September 2017 to May 2023 were retrospectively enrolled, including 111 males and 112 females, aged [M(Q1,Q3)] 57(21,66) years. According to the presence or absence of thromboembolism during follow-up, the patients were divided into thrombosis group (n=102) and non-thrombosis group (n=121). The clinical characteristics, laboratory characteristics, cytogenetics and other disease progression and survival of the two groups of patients were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 6 (3, 10) years. The influencing factors of thrombosis in JAK2V617F positive MPN patients were analyzed by using the Cox risk model. Results: Among 223 JAK2V617F positive MPN patients, 144 were polycythemia vera (PV), 51 were essential thrombocythemia (ET) and 28 were primary myelofibrosis (PMF). The mutation rates of ASXL1 and BCORL1 genes in the thrombosis group were 19.6% (20/102) and 6.9% (7/102), respectively, which were higher than those in the non-thrombosis group [9.1% (11/121) and 0.8% (1/121)] (both P<0.05). The proportion of monocytes, C-reactive protein (CRP), interleukin-1ß (IL)-1ß, IL-8 and tumor necrosis factor-ß (TNF-ß) increased in the thrombosis group were higher than those in the non-thrombosis group (all P<0.05). Multivariate analysis showed that age≥60 years (HR=2.132, 95%CI: 1.376-3.303, P=0.001), history of thrombosis (HR=3.636, 95%CI: 2.121-6.202, P<0.001), ASXL1 mutation positive (HR=2.245, 95%CI: 1.093-3.231, P=0.022) and elevated TNF-ß (HR=2.009, 95%CI: 1.113-3.624, P=0.021) were risk factors for thrombosis in JAK2V617F positive MPN patients. Conclusions: In addition to age, history of thrombosis and positive ASXL1 mutation, elevated TNF-ß is also an influencing factor of thrombosis in JAK2V617F positive MPN patients. Intervention of inflammation may have a certain effect on the prevention and treatment of thrombosis.

[Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer].

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.

[A case of giant pleural tuberculoma].

We retrospectively analyzed a rare case of giant pleural tuberculoma. The patient was a female, 62 years old, admitted to hospital for intermittent fever and hemoptysis. The CT scan of the chest and abdomen showed a mass in the right thoracic cavity, and the uneven surface of the bilateral fallopian tubes. Routine blood tests showed a decrease in platelets, white blood cells, and hemoglobin. The mass in the chest was finally confirmed as a tuberculoma by biopsy. The patient was diagnosed with tuberculosis more than 9 years ago and had been treated with anti-tuberculosis drugs for more than 9 years, which caused damage to the liver, bone marrow and other organs, and led to the drug-resistant tuberculosis, making diagnosis and treatment more complex.

[A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer].

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

[Focusing on the study of colorectal tumor and improving the detection rate of advanced adenoma].

The incidence of colorectal cancer in China is increasing year by year, and the mortality rate remains high. To reduce cancer-related social and economic burdens, awareness of and research on colorectal cancer is of great significance. It is necessary to explore the research on colorectal cancer diagnosis, endoscopic treatment, and prevention. Focuses should also be placed on actively screening for colorectal cancer and improving the advanced adenomas detection rate, thereby building a colorectal cancer prevention and treatment system which meets the national conditions of China.

[Correlation between the pre-and post-operative sagittal parameters and the quality of life in patients with degenerative and isthmic spondylolisthesis].

Objective: To assess the relationship between health-related quality of life (HRQOL) and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery, and to provide a biomechanical basis for improving the clinical prognosis of such patients. Methods: A retrospective analysis of 63 patients with lumbar spondylolisthesis who received lumbar fusion surgery in the Department of Spine Surgery, Tianjin Union Medical Center from December 2017 to June 2020 was carried out. There were 16 males and 47 females with a mean age of (59±8) years. Subgroup analyses were conducted based on disease type (degenerative lumbar spondylolisthesis (DS) and the isthmic spondylolisthesis (IS)) and HRQOL scores. Patients were evaluated post-operatively to observe the improvement of symptoms and quality of life. The relationship between operative related factors, HRQOL scores before and after surgery, and spino-pelvic sagittal parameters (including sagittal axis of the spine, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle (PT), sacral tilt angle, matching degree of pelvic incidence angle (PI) and lumbar lordosis angle (LL), lumbar 1 vertebra plumb line, upper lumbar curve, lower lumbar curve) in the two groups were analyzed. The correlation between the improvement of HRQOL scores and spino-pelvic sagittal parameters in the DS group and the IS group was analyzed and compared. Results: There were significant differences between postoperative HRQOL scores compared with those before the operation in both the DS and IS groups at three times of follow-up after the operation (all P<0.05). There was no difference in the last HRQOL score, the number of surgical segments, operation time and intraoperative blood loss between the two groups (all P>0.05). The parameters of PT and PI-LL in DS patients with VAS back pain score>3 and ≤3 were statistically different (13.7°±6.4° vs 26.6°±7.4°, 5.1°±8.2° vs 18.2°±13.1°, respectively, both P<0.05), similar results were obtained in IS patients (14.1°±6.9° vs 16.4°±8.7°, 2.9°±9.7° vs 6.8°±9.8°, respectively, both P<0.05). In addition, the parameters of PT and PI-LL between patients with ODI>20 and ≤20 were all statistically different in the two groups at the last follow-up after surgery (all P<0.05). The improvement of VAS back pain score in DS and IS groups was significantly related to the improvement of PT value, respectively (r=0.76, 0.78, both P<0.05). The PT, LL and PI-LL were significantly correlated with the ODI in the DS group (r=0.60, 0.62, 0.50, all P<0.05). There was also a correlation between the improvement of ODI and PT, LL and PI-LL in the IS group, respectively (r=0.22, 0.41, 0.76, all P<0.05). Conclusions: Certain correlation exists between the HRQOL and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery. For the treatment of lumbar spondylolisthesis and improvement of quality of life, the primary goal is to reconstruct the matching degree of the lumbar lordosis angle and PI, and to reduce the PT value to the normal range by tilting the pelvis forward.

[Comparative study of hypersensitive quantitative fecal immunochemical test and qualitative fecal occult blood test for colorectal cancer and advanced adenoma].

Objective: To evaluate the screening performance of hypersensitive quantitative fecal immunochemical test (hs-qFIT) and qualitative fecal occult blood test (FOBT) for colorectal cancer and advanced adenoma. Methods: Consecutive participants scheduled to undergo colonoscopy from April 2020 to April 2021 in Qilu Hospital of Shandong University were included in the study. All the participants were 50-75 years old and at moderate to high risk for colorectal cancer. Participants completed hs-qFIT and two kinds of qualitative FOBTs (colloidal gold method and chemical-immunization method) before colonoscopy. The sensitivities and specificities of hs-qFIT and two qualitative FOBTs for colorectal cancer and advanced adenoma were compared. Results: A total of 910 participants were enrolled in the study, including 451 males and 459 females, aged (59.6±6.4) years. There were 22 cases (2.4%) of colorectal cancer, 61 cases (6.7%) of advanced adenoma, 276 cases (30.3%) of non-advanced adenoma, 194 cases (21.3%) of non-adenomatous polyp, 85 cases (9.3%) of other colorectal lesion and 272 cases (29.9%) of non-colorectal lesion. The sensitivities of hs-qFIT for detecting colorectal cancer increased from 72.7% (95%CI: 49.6%-88.4%) to 100% (95%CI: 81.5%-100%) with cut-off value decreasing from 200 ng/ml to 10 ng/ml, and the sensitivities of both colloidal gold method and chemical-immunization method were 63.6% (95%CI: 40.8%-82.0%) (P=0.008). The detection stability of hs-qFIT for colorectal cancer was higher than colloidal gold method (P=0.016) and chemical-immunization method (P=0.031). The sensitivity for detecting advanced adenoma of hs-qFIT at 10 ng/ml was 52.5% (95%CI: 39.4%-65.2%), which was significantly higher than that of colloidal gold method (13.1%, 95%CI: 6.2%-24.8%, P<0.001) and chemical-immunization method (6.6%, 95%CI: 2.1%-16.7%, P<0.001). Conclusions: The sensitivity and detection stability of hs-qFIT for detecting colorectal cancer was higher than qualitative FOBT. Moreover, the sensitivity for detecting advanced adenoma can be further improved using a lower cut-off value.

[Analysis of the effectiveness of coracoid osteotomy and concentric coaxial reconstruction of the glenoid cavity in the treatment of recurrent anterior dislocation of the shoulder joint].

Objective: To investigate the clinical efficacy of the modified Latarjet procedure in the treatment of recurrent anterior subluxation of the shoulder by "coaxial co-arc" reconstruction of the glenoid cavity. Methods: The clinical data of 103 cases (106 shoulders) of recurrent anterior dislocation of the shoulder admitted to the First Affiliated Hospital of the Army Military Medical University from January 2005 to December 2020 were retrospectively studied. Out of these cases, 84 were males and 19 were females; 31 with left-sided injuries while 75 with right-sided injuries, with a mean age of (29.4±11.5) years (16-61 years). The preoperative anterior fear test was positive, and a modified Latarjet procedure was used to reconstruct the shoulder glenoid defect through a "coaxial co-arc". The Rowe score, simple shoulder test (SST) score, and Visual analogue scale (VAS) score of pain were used to assess the shoulder's function. Parameters such as the postoperative shoulder recurrent dislocation rate, shoulder body external rotation angle, and subscapularis muscle strength changes were recorded postoperatively. Moreover, radiographs and CT scans were used to check for the incidence of osteoarthritis (Samson-Prieto score). Results: After a mean follow-up of 9.0 years (1 to 16 years), bony healing occurred 3 to 6 months postoperatively. The Rowe score improved from 40.4±6.5 preoperatively to 93.2±2.5 (P<0.001), the SST score improved from 5.2±1.3 preoperatively to 10.1±1.5 (P<0.001), and the VAS pain score decreased from 3.5±1.9 preoperatively to 1.1±1.2 (P<0.001) at the final follow-up. The angle of lateral external rotation of the shoulder joint was 58.8°±15.6° preoperatively and 57.6°±14.5° postoperatively with no statistically significant difference (P>0.05). There was no statistically significant difference in the measurement of subscapularis muscle strength between the healthy side and the affected side (P>0.05). In 89.6% of patients after surgery, coaxial co-arc reconstruction of the shoulder glenoid was obtained, and the shoulder glenoid defect and postoperative inclusion angle were significantly improved compared with those before surgery (P<0.001). Postoperatively, new-onset osteoarthritis developed in 7 cases (7/98), arthritis progressed in 2 cases (2/8), incisional healing was poor in 2 cases (2/98), and revision surgery was performed in 2 cases (2/98) due to bone mass detachment. Conclusion: Coracoid osteotomy and concentric coaxial reconstruction of the glenoid cavity elicits adequate good clinical efficacy for cases of recurrent anterior shoulder dislocation, with low recurrence rates, low revision rates and low incidence of osteoarthritis.

[Clinical and histopathological features of immune checkpoint inhibitor-related myositis in patients with advanced non-small cell lung cancer].

Objective: To investigate the clinicopathologic features and outcome of myositis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Methods: The patients diagnosed with immune checkpoint inhibitor-related (ICI) myositis in the database of Respiratory Pathology Center of The First Affiliated Hospital, Guangzhou Medical University from June 2019 to December 2020 were retrospectively analyzed. We reported the muscle histology and main clinical manifestations of the patients in this study. Seven patients with advanced non-small cell lung cancer and ICI related myositis were examined; all of the patients were male, with a median age of 64 (range 42-79) years. Results: All seven patients developed myositis under therapy (three for pembrolizumab, three for sintilimab, and one for camrelizumab). Median delay between ICI initiation and myositis onset was 45 (range 15-176) days. Clinical manifestations were dominated by acute or subacute myalgia and limb weakness. Four patients had evidence of myocarditis. In all of the 7 patients, creatine kinase levels were elevated (median 2 354.4, range 468.6-19 709.2 U/L), while myositis-associated antibodies Ro-52 were positive in four patients. Muscle biopsy showed evident multifocal necrotic myofibers and infiltration of inflammation in two patients. Other patients only showed non-specific endomysial inflammation. Infiltration of inflammation mainly consisted of CD8+ T cells and CD68+ histocytes. After the identification of ICI related myositis, ICI treatment was withdrawn in all patients; 6 patients received corticosteroids therapy. All patients had shown marked clinical improvement. Conclusions: ICI myositis presents with remarkably homogeneous and unique clinicopathologic features, and half of the patients exhibit heightened risk for adverse cardiovascular events, which can be life-threatening if not treated in time. Timely identification of these patients, ICI withdrawal and rapid initiation of corticosteroids therapy can significantly improve patient outcome and/or save patients' lives.

[Investigation and case analysis of an occupational chronic benzene poisoning accident].

This article investigated an occupational chronic benzene poisoning incident that occurred in a sealing material factory in Hebei Province in September 2019, analyzed the clinical data of workers, to explore the causes of occupational chronic benzene poisoning, and summarize the diagnosis and treatment characteristics and treatment outcome. According to GBZ 68-2013 "Diagnosis of Occupational Benzene Poisoning", a total of 12 cases of occupational chronic benzene poisoning were diagnosed among the 20 workers, including 2 cases of occupational chronic mild benzene poisoning, 7 cases of moderate benzene poisoning, and 3 cases of severe benzene poisoning. Both mild and moderate poisoning patients had recovered after treatment. Severely poisoned patients had recovered more slowly, and the white blood cell count was still 2.0×10(9)-3.0×10(9)/L during the 1-year follow-up. This benzene poisoning incident was caused by illegal operations. The responsibility of the employer, the supervision of the administrative agency, and the awareness of personal protection of employees should be strengthened to avoid or reduce the occurrence of poisoning incidents and ensure the health of workers.