[Clinical analysis of 80 patients with oblique vaginal septum syndrome].

Objective: To investigate the clinical features, diagnosis and treatment of oblique vaginal septum syndrome (OVSS). Methods: The clinical data of 80 patients with OVSS admitted to The Second Hospital of Hebei Medical University from July 2005 to July 2023 were retrospectively analyzed. According to the classification system of OVSS proposed by Female Genital Anomalies Study Group, Chinese Obstetricians and Gynecologists Association in 2021, the patients were divided into four groups. The clinical manifestations, accompanied urinary system abnormalities, diagnosis and treatment methods and treatment outcomes were observed. Results: According to the above classification system, among the 80 patients with OVSS, 35 patients (44%, 35/80) were categorized as type Ⅰ, 33 patients (41%, 33/80) were categorized as type Ⅱ, 2 patients (3%, 2/80) were categorized as type Ⅲ and 10 patients (13%, 10/80) were categorized as type Ⅳ. The main onset symptom of patients was periodic abdominal pain (70%, 56/80), vaginal bleeding (20%, 16/80), dysuria or fecal impaction (15%, 12/80), vaginal mucopurulent discharge (10%, 8/80). The morbidity of combined urinary system abnormalities was 88% (70/80), and the most common urinary system abnormality was ipsilateral renal agenesis (81%, 65/80). Bilateral kidneys were normal in 13% (10/80) patients, and 6% (5/80) were combined with other urinary system abnormalities. A total of 74 patients underwent vaginal oblique septectomy or septum excision. Five of the 10 patients with type Ⅳ underwent hysterectomy on the cervical atresia side, 4 patients received hysteroscopy combined with cervicoplasty+oblique septotomy or septum excision, and one patient selected delayed menstruation. Two patients underwent laparoscopic resection of the dysplasia kidney and ectopic ureter which opening to the vagina. Eleven patients with endometriosis cyst, hydrosalpinx or empyema underwent laparoscopic surgery. Conclusions: The main symptom of type Ⅰ and Ⅳ patients is abdominal pain, while the main symptom of type Ⅱ and Ⅲ patients is bleeding. Magnetic resonance imaging (MRI) has advantages in the evaluation of complex OVSS, and MRI is recommended before operation to exclude other axial reproductive tract dysplasia and complex urinary system dysplasia. If there is leakage of urine, vaginal discharge or complex deformity, it is necessary to multidisciplinary discussion and formulate a reasonable surgical plan. The first treatment is related to the prognosis of patients especially children, and should be highly valued.

[Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice].

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) µg/mg vs. (0.974±0.060) µg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) µg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

[Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study].

OBJECTIVE: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. CONCLUSION: The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Chrysin induces osteogenic differentiation of human dental pulp stem cells.

OBJECTIVES: As an ideal cell source for tissue engineering and bone defect repair, dental pulp stem cells (DPSCs) have good osteogenic differentiation potential. Chrysin, a flavonoid extracted from oroxylum seeds, has been proven to promote bone formation of bone marrow stem cells. However, the effect of chrysin on osteogenic differentiation of DPSCs remains unclear. This study aimed to investigate the role of Chrysin in promoting osteogenic differentiation of DPSCs and in DPSC-based bone formation. MATERIAL AND METHODS: We investigated the effects of chrysin on DPSCs from patients by CCK-8 assay, Alizarin Red S staining, qPCR and Western blotting. The effects of chrysin on DPSC-based bone formation in a heterotopic osteogenesis model in nude mice and a rat calvarial defect model were also performed. Finally, we investigated the mechanism of chrysin-treated DPSCs by proteomics. RESULTS: Chrysin upregulated the expression of osteogenic proteins and induced osteogenic differentiation of DPSCs. Moreover, chrysin induced abundant ß-TCP-induced formation of mineralized bone tissue and promoted DPSC-based bone formation in a heterotopic osteogenesis model in nude mice and a rat calvarial defect model. Proteomics showed that upregulation of the Smad3 was closely related to osteogenic differentiation. Inhibiting of Smad3 activation by a Smad3 inhibitor could reverse the chrysin-mediated increases in the expression levels of osteogenic genes and osteogenic induction of DPSCs. CONCLUSIONS: Our study implies the intriguing potential of chrysin-treated DPSCs in bone regeneration and bone defect repair.

[Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis].

Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.

[Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses. CONCLUSION: The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.

[Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. RESULTS: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. CONCLUSION: Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

[Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases].

Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.

[Clinical features and prognosis of patients with leptomeningeal metastases].

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95%CI:2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival (P<0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

[A multicenter, randomized, double-masked, placebo-controlled trial of compound wild chrysanthemum eye masks for mild and moderate dry eye].

Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer Ⅰ test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer Ⅰ test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).

LncRNA SNHG4 promotes neuroblastoma proliferation, migration, and invasion by sponging miR-377-3p.

Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.

Knockdown of microRNA-103a-3p inhibits the malignancy of thyroid cancer cells through Hippo signaling pathway by upregulating LATS1.

MicroRNA (miR)-103a-3p has been shown to be involved in the development and progression of several types of cancer. However, the role of miR-103a-3p in thyroid cancer remains unclear. This study investigated the effects of miR-103a-3p on the biological characteristics of thyroid cancer cells and related mechanisms. In the present study, we found that the expression of miR-103a-3p was increased in thyroid cancer tissues compared to that in non-cancerous tissues. Additionally, the expression of miR-103a-3p in thyroid cancer cell lines (TPC-1, SW579, BHT101, K1) was markedly higher than that in the human thyroid cell line (Nthy-ori3-1). Silencing of miR-103a-3p obviously inhibited proliferation, migration, and invasion and promoted apoptosis of BHT101 cells. miR-103a-3p upregulation promoted the proliferation, migration, and invasion and inhibited apoptosis of K1 cells. Mechanistically, LATS1 was identified as a functional target of miR-103a-3p, and miR-103a-3p negatively regulated LATS1 expression. miR-103a-3p knockdown (or upregulation) partially reversed the effects of LATS1 knockdown (or overexpression) on proliferation, apoptosis, migration, and invasion of thyroid cancer cells. LATS1 knockdown inhibited the phosphorylation of YAP in BHT101 cells and promoted the nuclear translocation of YAP. Whereas, miR-103a-3p downregulation reversed the inhibitory effect of LATS1 knockdown on the Hippo signaling pathway. Moreover, overexpression of LATS1 induced YAP phosphorylation in K1 cells and inhibits nuclear translocation of YAP, and the upregulation of miR-103a-3p reversed this effect. The knockdown of miR-103a-3p inhibited tumor growth and progression in vivo. Taken together, knockdown of miR-103a-3p inhibits proliferation, migration, and invasion and promotes apoptosis of thyroid cancer cells through the Hippo signaling pathway by upregulating LATS1.

Short communication: A decrease in diameter of milk fat globules accompanies milk fat depression induced by conjugated linoleic acid supplementation in lactating dairy cows.

Milk fat is secreted from the mammary gland in the form of milk fat globules (MFG). Although milk fat depression has been studied since the beginning of the last century, the extent to which this phenomenon alters MFG synthesis is not fully understood. The aim of this study was to evaluate the effect of conjugated linoleic acid (CLA) on the size and distribution of MFG during milk fat depression in dairy cows. Twelve Holstein cows in mid lactation (145 ± 31 d in milk, 583 ± 34.6 kg of body weight, and 27.2 ± 2.4 kg of milk/d) were randomly assigned to a control diet or control plus Ca-protected CLA at 15 g/kg of dry matter for a 6-d period. The average diameter and particle size distribution of MFG were measured using a Mastersizer 3000 laser particle size analyzer (Malvern Instruments Ltd., Malvern, UK). Feeding CLA did not affect dry matter intake (16.2 ± 0.4 kg/d), milk production (28.4 ± 0.4 kg/d), milk protein, or lactose, but it decreased milk fat content (3.46 vs. 2.52%). In addition, surface area-related mean diameter of fat globules in cows fed CLA was lower compared with controls (3.02 vs. 3.45 µm). The percentage of large fat globules decreased and that of small fat globules increased in response to CLA. Overall, the data suggest that the milk fat depression induced by CLA is accompanied by a decrease in average diameter of MFG.

[Early containment strategies and core measures for prevention and control of novel coronavirus pneumonia in China].

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.

[Report of breast cancer incidence and mortality in China registry regions, 2008-2012].

Objective: The registration data of local cancer registries from 2008 to 2012 were collected by National Central Cancer Registry to estimate the incidence and mortality of female breast cancer in China. Methods: Data from 135 registries were qualified and selected in the final analysis, and each registry at least has submitted data from 2010 to 2012. Cancer incidence and mortality analyses were stratified by area (urban/rural, eastern/middle/western areas) and age group. The age composition of standard population of Chinese census in 2000 and Segi's population were used for age-standardized incidence and mortality in China and worldwide, respectively. Results: A total of 135 registries were recruited in the analysis, covering 629 333 910 person-years (382 669 450 in urban and 246 664 460 in rural). About 13, 258 cases of female breast cancer were diagnosed and 32 205 cases were dead between 2008 and 2012. Female breast cancer incidence was 42.67/100, 000 and age-standardized rate calculated by worldwide standard population was 28.87/100, 000. The crude incidence of urban area was 51.85/100, 000, higher than 28.29/100, 000 of rural area, and the crude incidence of eastern area was 46.35/100, 000, higher than 36.38/100, 000 of middle area and 27.60/100, 000 of western area. The age-specific incidence increased with age and reached the peak at age 55-59 (96.36/100, 000), and declined at age 60. The age-standardized incidence rate by Chinese standard population increased 30.56% from 2003 to 2012. The increase rate of rural area was 72.32%, faster than 23.48% of urban area. Female breast cancer mortality was 10.36/100, 000 and the age-standardized rate calculated by worldwide standard population was 6.61/100, 000. The crude mortality of urban area was 11.64/100, 000, higher than 8.36/100, 000 of rural area, and the crude mortality of eastern area was 10.81/100, 000, higher than 7.38/100, 000 of middle area and 9.90/100, 000 of western area. The age-specific incidence increased with age and reached the peak at age above 85 (61.25/100, 000). Age-standardized incidence rate by Chinese standard population remained stable during the period of 2003-2012 (6.23%). The mortality rate mainly increased in rural area (54.94%), while decreased 2.32% in urban area over the 10 years. Conclusions: Although the incidence and mortality of breast cancer in China are comparatively low worldwide, in China the incidence and mortality of female breast cancer have rose to the first and sixth place respectively among all the female cancers. The disease burden of breast cancer is very different between urban and rural area. Therefore, the targeted measure and strategy of control and prevention according to the area difference are needed.

[Female reproductive system dysplasia: a clinical study of 924 cases].

Objective: To explore the relationship between different types of female reproductive system dysplasia and age of visit, clinical manifestations, common types of combined malformations and endometriosis. Methods: The patient's medical records in the Second Hospital of Hebei Medical University from December 2002 to June 2016 were collected and retrospectively analyzed. Results: Among 924 cases of genital tract dysplasia, uterine dysplasia (65.3%, 824/1 261) was the most common, followed by vaginal dysplasia (28.3%, 357/1 261), hymen atresia and urogenital fistula (3.7%, 47/1 261), and cervical dysplasia (2.6%, 33/1 261). (1) The youngest age was in patients with hymen atresia and urogenital fistula, with a median of 14.5 years old, while the older age were in patients with uterine, vaginal and cervical dysplasia, with median age of 25.0, 24.0 and 23.0 years old, respectively. (2) The clinical manifestations were lack of specificity, mainly abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history. (3) About other systemic malformations, urological malformations were the most common (4.8%, 44/924), followed by spinal malformations (0.5%, 5/924), inguinal hernia (0.4%, 4/924), heart malformations (0.2%, 2/924), cleft lip and palate (0.2%, 2/924). Oblique vaginal septal syndrome and MRKH syndrome were the most likely to be associated with other system malformations. (4) About combination with endometriosis, there was no significant difference between obstructive genital tract malformations (2.3%, 9/385) and non obstructive genital tract malformations (1.7%, 9/539; P=0.469). Conclusions: Female reproductive system dysplasia is the most common in uterine dysplasia, followed by vaginal dysplasia, hymen atresia and urogenital fistula, and cervical dysplasia. The age of visit is generally older, often found by abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history;and could be combined with a variety of other system malformations, most seen by urinary system malformations,there is also the risk of endometriosis.

[Study of genetic etiology in fetuses with severely short limbs in the first and second trimester using whole exome sequencing].

Objective: To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods: Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results: No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions: In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.

[The predictive accuracy of fine needle aspiration and BRAF V600E mutation in diagnosis of papillary thyroid carcinoma].

Objective: To evaluate the predictive accuracy of fine needle aspiration (FNA) and BRAF V600E mutation in distinguishing papillary thyroid carcinoma and other thyroid nodules. Methods: This retrospective cohort study included 93 patients with papillary thyroid carcinoma who treated at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University, College of Medicine from September 2016 to May 2018. There were 21 males and 72 females with age of (43.2±11.3) years (range: 19 to 67 years). All the patients got the examinations of FNA and BRAF V600E mutation by Amplification Refractory Mutation System, and subsequently underwent thyroid surgeries. The results of cytopathology, frozen section and pathology were collected and analyzed. The predictive accuracy of FNA cytology and BRAF V600E mutation was calculated. Results: In the 93 collected cases, 91 were diagnosed as papillary thyroid carcinoma postoperation, and the accurate predictive rate was 97.8%. Subgroup analysis was performed according to Bethesda System, the predictive rates were: unsatisfactory (Ⅰ) 6/6, benign (Ⅱ) 0/0, atypia of undetermined significance or follicular lesion of undetermined significance (Ⅲ) 16/17, follicular neoplasm or suspicious for follicular neoplasm (Ⅳ) 97.2% (35/36), suspicious for malignancy (Ⅴ) 100% (28/28), and malignant (Ⅵ) 6/6, respectively. Conclusion: Thyroid nodules with BRAF V600E mutation can be strongly speculated as papillary thyroid carcinoma.

[Analysis of the patterns of female breast cancer incidence in Shanghai, 2003-2012].

Objective: To analyze the patterns of female breast cancer and their incidence in Shanghai during 2003-2012, and to compare them with international data. Methods: The data of female breast cancer cases diagnosed between 2003 and 2012 were collected from the Shanghai Cancer Registry. The record of cancer cases included the patient's name, gender, date of birth, permanent and residential address, diagnosis site or name, histological type, date of first diagnosis, diagnostic basis and diagnostic stage, etc. Data source of cancer incidence of World, Developed Countries, Developing Countries, East Asia and China in 2012 sourced from GLOBOCAN 2012 database of the WHO International Agency for Research on Cancer (IARC); and the data of USA during 2008-2012 was collected from SEER 18 database from Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (NCI). Incidence indicators of Shanghai female breast cancer were calculated, including the average cases, median age, average age, proportion, crude rate, age-specific rate and age-standardized rate. Results: During 2003-2012, 41 991 new cases of female breast cancer were diagnosed in Shanghai, with an average of 4 199 cases per year, accounting for 17.23% among total new female cancer cases, ranking first in female cancer incidence in Shanghai during 2003-2012, with a crude incidence rate of 60.90 per 100 000 and an age-standardized incidence rate of 33.90 per 100 000. During 2008-2012, an average 4 528 new cases of female breast cancer was diagnosed per year in Shanghai, with 16.97% among total female cancer cases. The median age was 56 years old and the mean age was 57.73 years old. The crude rate was 64.23 per 100 000 and the age-standardized rate was 35.00 per 100 0000, which was higher than those of China (22.1 per 100 000), Eastern Areas (27.0 per 100 000) and Developing Counties (31.3 per 100 000), and lower than that of World (43.1 per 100 000), and Yellow Race Population of USA (68.77 per 100 000). During 2003-2007, on average, 3 869 new cases of female breast cancer were diagnosed per year in Shanghai, accounting for 17.54% of total female cancer cases. The median age was 53 years old and the mean age was 56.44 years old. The crude rate was 57.42 per 100 000 and the age-standardized rate was 32.69 per 100 000. There was a continuing peak stage spanned 25 years old from 50 to 74 years old, during 2008-2012. Compared with those of 2003-2007, the beginning age group of the continuing peak stage was delayed for 5 years old and the ending age group was delayed for 10 years old. Conclusion: The age-standardized incidence rate in Shanghai was higher than those of China, Eastern Areas and Developing Counties, and lower than that of World, and that of Yellow Race Population of USA; Compared with 2003-2007, the crude rate and age-standardized rate increased, the median age, mean age and the beginning and ending age group of the continuing peak stage were delayed.

[Preliminary experience with transoral endoscopic thyroidectomy via vestibular approach: a report of 150 cases in a single center].

Objective: To summarize the preliminary experience with transoral endoscopic thyroidectomy via vestibular approach (TOETVA). Methods: A total of 150 consecutive patients with thyroid disease underwent TOETVA from November 2014 to February 2017 at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine. The patients were comprised of 138 females and 12 males. The mean age of the patients was (31.7±7.6) years (ranging from 15 to 51 years). There were 108 patients of differential thyroid carcinoma (T1 or T2 ≤3 cm, cN0 or cN1a, M0) and 42 patients of benign thyroid disease (solid nodule ≤6 cm). The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, complications and results of follow-up. Results: Two cases were converted into open surgery due to an incredible unexpected tumor size and tracheal invasion, respectively. One hundred and three patients with papillary carcinoma underwent transoral central neck dissection (CND), with the mean operation time of (146±34) minutes for hemithyroidectomy with CND, and (187±36) minutes for total or near total thyroidectomy with CND. The mean number of lymph node yields was 8.2±4.7, and the lymph node metastasis rate was 41.7% (43/103). Regarding postoperative complications, transient hoarseness occurred in 3 patients, and permanent recurrent laryngeal nerve occurred in 2 patients. One patient had local infection or transient mental nerve palsy. Transient hypocalcemia occurred in 31.8% of 22 patients who underwent total, near-total, or subtotalthyroidectomy, and no permanent hypocalcemia was registered. Mean hospital stay after operation was (3.5±0.6) days (ranging from 2 to 5 days). Mean follow-up period was (11.5±7.8) months (ranging from 1 to 28 months), no recurrence or metastasis occurred. Conclusions: TOETVA is feasible and safe for strictly selective patients. It brings perfect cosmetic effect. Long-term follow-up and further study is needed to assess its curative effect.