[Incidence and mortality of endometrial cancer in China, data from China Cancer Registry Annual Report, 2004-2017].

Objective: To analysis the incidence rate and mortality rate of endometrial cancer in China from 2004 to 2017 according to the data from China Cancer Registry Annual Report. Methods: The incidence and mortality data of endometrial cancer were extracted from the China Cancer Registry Annual Report 2004 to 2017, and the incidence, mortality, number of new cases, number of deaths were extracted according to the region (national, urban, rural and eastern, middle and western areas) and the age composition of population to estimate the incidence and mortality of endometrial cancer nationwide. The age-standardized incidence rate and mortality rate were calculated based on the Chinese standard population in 2000 (ASIRC, ASIRW) and Segi's world population (ASMRC, ASMRW). Join Point regression was used to calculate the annual percentage change of morbidity rate, and Cochran-Armitage trend test was used to analyze the changing trend of morbidity and mortality. Results: From 2004 to 2017, the number of women covered by the China Cancer Registry Annual Report has increased from 35 571 657 to 215 201 995, and the total population of the covered areas has increased from 5.53% to 31.39%. The crude incidence rate of endometrial cancer increased from 6.20/100 000 to 10.06/100 000, and showed an upward trend over time (P<0.001). After adjusting for age, ASIRC increased from 5.75/100 000 in 2004 to 6.79/100 000 in 2017, and ASIRW increased from 5.60/100 000 in 2004 to 6.56/100 000 in 2017, both showing an upward trend over time (all P<0.001). The crude incidence rates in urban area and rural area were respectively 10.89/100 000 and 9.25/100 000 in 2017, and the ASIRC was higher in urban than rural areas (7.14/100 000 vs 6.43/100 000) after adjusting for age. The ASIRW was higher in eastern areas than middle areas and western areas (7.16/100 000 vs 6.44/100 000 vs 5.60/100 000). The incidence rate in rural areas showed more significant growth than urban areas [annual percent change (APC): 3.2% vs 0.7%, P<0.001]. The age-specific incidence rate increased with age and reached a peak in the age group of 50-54 years (25.70/100 000). Incidence rate in the under-40 age group increased more in rural areas than in urban areas (69.84% vs-7.09%). From 2004 to 2017, the age-standardized mortality rate shows a decreasing trend, with the ASMRC from 1.83/100 000 to 1.47/100 000, and the ASMRW from 1.81/100, 000 to 1.46/100, 000. There was no significant difference between urban and rural areas in mortality of endometrial cancer. Age-specific mortality rates increased with age, reaching a peak in the age group 85 years and older (13.16/100 000). Conclusions: Recent years, there was an increasing incidence rate of endometrial cancer in China. Especially in rural areas, the incidence rate of endometrial cancer is increasing rapidly in young women under 40 years of age. There were differences between urban and rural areas and regions in the incidence rate of endometrial cancer. The incidence rates of endometrial cancer in some high-income cities have occupied the first place of female reproductive system malignant cancers. The age-standardized mortality rate of endometrial cancer shows a decreasing trend.

[Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma].

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

[Colorectal cancer with ß-catenin protein expression deficiency: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and molecular characteristics of ß-catenin-deficient colorectal cancer. Methods: The clinical, pathological and molecular features of 11 colorectal cancers with ß-catenin protein loss diagnosed at the 960th Hospital of People's Liberation Army of China, from January 2012 to November 2022 were analyzed. Results: Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. ß-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of ß-catenin protein expression. Conclusion: ß-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

[Prognostic nutritional index application value for acute-on-chronic liver failure co-infection].

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

[Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma].

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34ßE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34ßE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

[Migratory pulmonary ground glass opacities caused by SARS-CoV-2 infection in a patient on B-cell depletion therapy].

In immunosuppressed individuals, the manifestation of viral pneumonia due to SARS-CoV-2 infection differs from that in healthy individuals. We reported a unique case of a 58-year-old male patient with B-cell depletion following treatment with the anti-CD20 monoclonal antibody. He presented to the Department of Pulmonary and Critical Care Medicine with complaints of intermittent fever and cough for three months, aggravated by shortness of breath for one month. He was previously diagnosed with stage IVA follicular lymphoma in April 2022 and underwent chemotherapy with Obinutuzumab (anti-CD20 monoclonal antibody). His last treatment was on November 3, 2022. On December 20, 2022, after contact with a SARS-CoV-2-infected person, he exhibited symptoms of fever peaking at 39.0 ℃, cough, and sputum production. A positive SARS-CoV-2 nucleic acid result was confirmed from a pharyngeal swab. Nine days later (December 29, 2022), the patient still had a fever. Chest CT showed multiple small pieces of ground glass opacities (GGOs) in both lower lungs. The diagnosis of viral pneumonia due to SARS-CoV-2 infection was confirmed. After five days of treatment with nirmatrelvir/ritonavir (Paxlovid) and intravenous dexamethasone (5 mg/d), his fever subsided. However, a subsequent chest CT on January 9, 2023 showed partial resorption of multiple GGOs in both lungs, accompanied by novel focal lesions. The patient developed a fever again on January 29, 2023, after which he had recurrent symptoms of fever, cough, and sputum, with intermittent short courses of antibiotics and dexamethasone, which never completely resolved. Multiple chest CTs during this period showed recurrent GGOs and consolidations in both lungs, demonstrating a migratory pattern. The patient was admitted to our hospital on March 7, 2023, with a peripheral blood test suggesting lymphocytopenia, a CD19+B lymphocyte count of zero, and negative IgG and IgM for SARS-CoV-2. A bronchoscopy and bronchoalveolar lavage fluid (BALF) analysis indicated a significantly elevated lymphocyte percentage and the presence of SARS-CoV-2 nucleic acid. Given the three-month history of chronic fever and respiratory symptoms, changing bilateral pulmonary infiltrates, and lack of SARS-CoV-2 humoral immunity, a diagnosis of persistent SARS-CoV-2 infection was considered. Subsequent treatment with Paxlovid for 15 days resulted in the resolution of all symptoms. A follow-up chest CT one month later showed almost complete normalization.

[A case of lung adenocarcinoma with markedly elevated amylase in airway secretions].

A 45-year-old male patient was admitted to the hospital because of intermittent cough and expectoration for more than 1 year, worsened by dyspnea for 2 months, and was finally diagnosed with lung adenocarcinoma. The CT scan of the chest revealed lesions of diversity with fibrosis, mass and effusion, but his severe cough limited biopsy of the lesions. The difficult process of diagnosis was aided by the further analysis of the sputum, which showed significantly elevated amylase without any evidence of pancreatic disease. The cough was relieved by intravenous pumping octreotide acetate, and both CT-guided lung biopsy and transbronchial biopsy revealed the lung adenocarcinoma. The diagnostic process of this case provided a helpful diagnostic thinking and demonstrated the rare clinical features of lung adenocarcinoma.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].

Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737(95%CI:0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709(95%CI:0.602 to 0.815), and the AUC of the ROC curve for 24-month restenosis was 0.702(95%CI:0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.

[Clinical characteristics and correlative factors of dry eye disease associated with graft-versus-host disease].

Objective: To investigate the clinical features of dry eye disease in patients with graft-versus-host disease (GVHD) and to identify the correlative factors that contribute to its severity. Methods: It was a retrospective case series study. A total of 62 patients with dry eye disease caused by GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) were recruited from the First Affiliated Hospital of Soochow University between 2012 and 2020. The study population comprised 38 males (61%) and 24 females (39%), with an average age of (35.29±11.75) years. Only the right eye of each patient was evaluated. The patients were divided into two groups based on the severity of corneal epitheliopathy: a mild group (15 eyes) and a severe group (47 eyes). Demographic information, including gender, age, primary disease, type of allogeneic HSCT, donor-to-recipient information, source of hematopoietic stem cells, systemic GVHD, and the time from HSCT to the first visit, was collected. Ophthalmologic assessments, including the Schirmer Ⅰ test, tear breakup time, corneal epithelial staining, and eye margin assessment, were performed during the first visit to the ophthalmology department and compared between the two groups. Results: The average time from HSCT to the first visit to the ophthalmology department among the 62 patients was (20.26±13.09) months. The median corneal fluorescein staining score was 4.5 points. In the mild group, the main characteristic of corneal staining was scattered punctate staining in the peripheral region in 80% of cases, while in the severe group, corneal staining fused into clumps in both the peripheral region (64%) and the pupillary zone (28%). Results of the Schirmer Ⅰ test were significantly lower in the severe group compared to the mild group (P<0.05). The median total eyelid margin score in the severe group was higher than that in the mild group [9 (7, 12) points vs. 6 (5, 8) points] (P<0.05). The median eyelid congestion score in the severe group was, also higher than that in the mild group [2 (1, 3) points vs. 1 (0, 2) points] (P<0.05). The compatibility between the blood types of the donor and recipient was found to be statistically significant (P<0.05). There was no significant difference in gender, age, family relationship, human leukocyte antigen matching, gender consistency, source of hematopoietic stem cells, or the occurrence of systemic GVHD between the two groups (P>0.05). Conclusions: Patients in the mild group had scattered punctate corneal staining in the peripheral region, while those in the severe group showed fusion of corneal staining into clumps in both the peripheral and pupillary zones. The severity of dry eye disease caused by GVHD was strongly correlated with eyelid margin lesions. A higher degree of eyelid margin lesions indicated more severe dry eye disease caused by GVHD. Additionally, compatibility between the blood types of the donor and recipient may play a role in the development of GVHD-associated dry eye.

[Three cases of occupational acute trimethyltin chloride poisoning].

Trimethyltin chloride is a highly toxic substance, which is absorbed through respiratory tract, skin and digestive tract, with central nervous system injury as the main clinical manifestations, and can be accompanied by damage to various organs. In this paper, the treatment process of 3 patients with acute trimethyltin chloride poisoning was reviewed, and their clinical manifestations, auxiliary examination, diagnosis and treatment were analyzed. Three patients were misdiagnosed as mental abnormality, encephalitis, and hepatic encephalopathy in different hospitals in the early stage of medical treatment, suggesting that clinicians should pay attention to the occupational contact history of poisoned patients and conduct toxicant detection in time to avoid misdiagnosis and mistreatment.

[Predictive value of hemoglobin glycation index for chronic kidney disease].

Objective: To investigate the influence of hemoglobin glycation index (HGI) on the risk of incident chronic kidney disease (CDK) among nondiabetic patients. Methods: Prospective cohort study. At baseline, a total of 7 407 nondiabetic patients without a history of CKD from Pingguoyuan Community of the Shijingshan District in Beijing were included from December 2011 to August 2012, who were then divided into three groups according to the tertiles of their baseline HGI levels. The CKD incidence rate was compared among the different HGI groups at last follow-up. Cox multivariable regression was applied to evaluate whether HGI measures predicted CKD risk. Test for trend across tertiles were examined using ordinal values in separate models. Results: The mean age of the subjects was (56.4±7.5) years, and 4 933 (66.6%) were female. At mean follow-up of 3.23 years, 107 (1.4%) individuals developed CKD. The incidence of CKD was gradually increasing from the low to high HGI groups [1.1% (28/2 473) vs. 1.2% (31/2 564) vs. 2.0% (48/2 370), P=0.016]. In the multivariate Cox regression analysis, after adjustment for potential confounders, the high HGI group had a 68.5% increased risk of CKD compared with the low HGI group (HR=1.685, 95%CI 1.023 to 2.774). CKD risk increased with increasing HGI tertiles (P for trend=0.028). Conclusion: High HGI is associated with an increased risk for CKD in the nondiabetic population, indicating that HGI may help identify individuals at high risk for CKD.

[Identification of rare variants in exons of NLRC4 gene in patients with type 1 diabetes and their impact on gene function].

Objective: To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function. Methods: A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q1, Q3)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their ageï¼»M（Q1，Q3）］was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1ß in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results: The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>T、c.1564T>Cc.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1ß secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q1, Q3)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010). Conclusions: NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1ß. This result suggests that NLRC4 rare variants may have an impact on gene function.

[Standardization of spirometry updated in China and international: comparison and interpretation of the key updates].

Standardization of spirometry was jointly updated by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2019. Similar technical standards for spirometry recommended by the Chinese Thoracic Society (CTS) and/or the Chinese Association of Chest Physicians (CACP) are widely used in China. We compared the key similarities and differences of these recommendations and interpreted the key updates. The ATS/ERS 2019 updates expanded the scope of indications for spirometry and recommended the contraindications based on the pathophysiological perspective, while contraindications recommended by the CTS were based on the severity of contraindications. ISO 26782∶2009 standards were applied by the ATS/ERS 2019 to evaluate the performance quality (reliance for accuracy, repeatability, etc.) of spirometers, while standards adopted 24/26 waves suggested by the ATS 1994 was used by the CTS. The ATS/ERS 2019 also included the performance quality control criteria for 3-L calibration syringe, operator training and attainment and maintenance of competency, grade"U", system warning messages, instructions to patients, and standardized operator comments. Some of these criteria in the CTS were not explained in detail. However, the CTS/CACP emphasized that the spirometry record should report the indices of forced inspiratory phase and small airway function, those are not clearly required in the ATS/ERS 2019. In comparison, the ATS/ERS 2019 has stricter criteria for FEV1 and FVC acceptability than the CTS and more detailed explanations. Those outstanding parts are worth referencing for the updated version of the CTS in the future, while the criteria that combine our own conditions need to be retained and popularized.

[Investigation on status of lung cancer cough management and concept and practice of lung cancer cough management in Chinese medical providers].

Objective: Investigate the current situation of lung cancer cough diagnosis and treatment and the awareness of related issues among Chinese medical providers. Methods: Doctors, nurses, pharmacists from the oncology department, respiratory department, or general department were investigated using an electronic questionnaire from January 29 to March 29, 2021. There were 25 questions about lung cancer in the questionnaire. The questionnaire was including the most common accompanying symptoms in patients with lung cancer, the incidence of lung cancer-related cough, the assessment of the proportion of central antitussive drugs, and the commonly used central antitussives. Results: Questionnaires from 2 424 medical providers were collected from 402 hospitals in 21 provincial administrative units. Cough was the most common symptom in lung cancer. Most physicians believed that the incidence of lung cancer-related cough was 51%~75%, while the proportion of patients satisfied with the treatment was only 11%~20%. The evaluation of lung cancer-related cough was seriously insufficient. The leading cause of lung cancer-related cough was tumors. And the main problem was the inadequate antitussive effect of drugs in lung cancer-related cough management. The proportion of central antitussive medication usage in the secondary and tertiary hospitals was 93.9% and 92.0%, significantly higher than 75.0% in Primary hospitals (χ²=8.390, P=0.015). The proportion of the physicians who underhanded that codeine is at risk of addiction was 76.6% and 72.0% in the secondary and tertiary hospitals, which were significantly higher than 53.9% in Primary hospitals (χ²=9.240, P=0.010). In different occupations, the proportions of doctors and pharmacists who knew the risk of addicting to codeine were 73.0% and 82.6%, which were significantly higher than the 66.4% of nurses (χ²=21.200, P<0.001). The Chinese medical providers were lack of training about the basic knowledge of using central antitussive medication. Conclusions: The proportion of patients who were satisfied with the effect of cough treatment is low. The medical staff did not have enough awareness of this. There was an urgent need to develop a consensus and standardize lung cancer cough diagnosis and treatment in China.

[Investigation of epidemiological characteristics and influencing factors on dust-exposed working age of pneumoconiosis cases in a city].

Objective: To investigate epidemiological characteristics and influencing factors on dust-exposed working years of pneumoconiosis cases in Yantai. Methods: In January 2020, By Cluster sampling way, Using descriptive statistics to analyze dust-exposed working years of the reported 3307 new cases of pneumoconiosis from 2009 to 2019 in Yantai. Analyzing the variation trends by the chi-square trend test. Analyzing single fator by chi-square test. Using multiple classification Logistic Regression analysis to analyze multiple influencing factors. Results: The dust-exposed working age of pneumoconiosis cases decreased by years (P<0.05) . The starting age of dust exposure of cases increased year by year, while positively correlated with the dust-exposed working age (r=-0.217, P<0.05) . The years of dust exposure, starting age of dust exposure, industry, type of economy and scale of enterprise were main influence factors on the dust-exposed working age of pneumoconiosis cases. Conclusion: We should strengthen the management on prevention and control condition of pneumoconiosis in metal smelting and processing industry and privately-owned, small and micro enterprises, and pay attention to workers starting exposed to dust in the age of ≥28 years old.

MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-ß1/Smad3 signaling pathway.

It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-ß (TGF-ß) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-ß1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-ß1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.

[Effect of polyphyllin â ¡ on the proliferation, invasion and chemosensitivity to temozolomide of glioma cells].

Objective: To investigate the effect and mechanism of Polyphyllin Ⅱ on the proliferation, invasion and chemosensitivity of glioma cells. Method: CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of Polyphyllin Ⅱ on the proliferation and invasion of glioma cells (T98G and LN18), respectively. The expression of E-cadherin, Snail and O6-methylguanine DNA methyltranferase (MGMT) were quantified by Western blot analysis. Results: Polyphyllin Ⅱ could inhibit the proliferation of glioma cells in a time- and does-dependent manner. The half maximal inhibitory concentration (IC(50)) of T98G at 24 h, 48 h and 72 h were (5.82±0.32), (3.57±0.07) and (1.48±0.35) µmol/L, respectively. The IC(50) of LN18 at 24 h, 48 h and 72 h were (6.83±0.11), (4.28±0.29), (2.66±0.22) µmol/L, respectively. After being treated with 2 µmol/L, 4 µmol/L and 6 µmol/L Polyphyllin Ⅱ for 24 h, the percentage of invasive cell area in the chamber area was lower than those in T98G and LN18 control groups (P<0.05). Western blot analysis showed that compared with glioma cells without Polyphyllin Ⅱ treatment, the expression of E-cadherin in T98G and LN18 was higher (F=85.56, P<0.05; F=60.80, P<0.05), but the expression of snail was lower (F=25.34, P<0.05; F=48.28, P<0.05). When temozolomide was used in combination with Polyphyllin Ⅱ at different concentrations, the coefficient of drug interaction (CDI) was less than 1. Western blot showed that MGMT expressions in T98G and LN18 were inhibited compared with glioma cells without Polyphyllin Ⅱ treatment (F=40.38, P<0.05; F=48.44, P<0.05). Conclusion: Polyphyllin Ⅱ can inhibit the proliferation and invasion of glioma cells, and improve its sensitivity to Temozolomide.