Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open-Label, Prospective, Pilot Study.

PURPOSES: This study investigated the feasibility of adalimumab (ADA) dose reduction and withdrawal strategy in children with stable pediatric non-infectious uveitis (PNIU). METHODS: This open-label prospective pilot trial recruited 18 stable PNIU patients (33 eyes) between two and eighteen years old who were treated with standard doses of ADA (20/40 mg every 2 weeks) plus oral methotrexate. The interval of ADA injection was extended to 4 weeks and followed up for 24 weeks. If the uveitis remained stable, ADA was discontinued and followed up for another 24 weeks. ADA was considered successfully stopped if no relapse occurred during this period. The relapse-free survival rate, best corrected visual acuity (BVCA), anterior chamber cell (ACC), vitritis, macular thickness (MT), and serum ADA levels were evaluated. Approval Number: 2021KYPJ201. ClinicalTrials.gov identifier: NCT05155592. RESULTS: The relapse-free survival rate was 22.2% (4/18) at 48 weeks. 33.3% (6/18) of patients relapsed when ADA was given every 4 weeks, while 44.5% of patients (8/18) relapsed after ADA was stopped. The four patients successfully withdrawn from ADA were all diagnosed with BD. No statistically significant differences (p > 0.05) were observed in BCVA and MT between baseline and final follow-up. The proportion of ACC and vitritis exhibited an upward trend (p < 0.05) during follow-up. Serum ADA gradually decreased to zero during follow-up in both non-recurrence and recurrence groups. CONCLUSIONS: In PNIU children who reached remission for 6 months, ADA dose reduction and withdrawal were associated with a high risk of inflammation recurrence. Timely adjustment of ADA to the last effective dosage frequency can regain control of the inflammation. Detection of ADA serum levels in patients with recurrence may help find the appropriate interval of ADA use.

[Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis].

Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.

[Clinical experience of REcanalisation and balloon-oriented puncture for Re-insertion of long- term dialysis catheter in nonpatent central veins].

It is difficult to insert long-term dialysis catheters after severe stenosis or occlusion of the internal jugular vein and innominate vein. We used REcanalisation and balloon-oriented puncture for Re-insertion of dialysis catheter in nonpatent central veins (REBORN) in seven patients with severe central venous lesions, and all patients were inserted with long-term dialysis catheters successfully. None had severe complications such as pneumothorax, hemothorax, or pulmonary embolism during operation. All catheters functioned well after postoperative follow-up of 2 months. REBORN provides a novel approach to establish difficult dialysis pathways.

[Study on the development of public health and safety literacy assessment scale for university freshmen].

Objective: To develop a measurement scale for the public health and safety literacy of university freshmen. Methods: Item pooling was conducted through literature review and in-depth interview with public health experts, and a nominal group was organized to develop the initial items to form the questionnaire. A total of 250 freshmen were randomly selected to complete the questionnaire, and the assessment of psychometric properties were performed to carry out item reduction by using classical test theory and item response theory. Exploratory factor analysis method (EFA) was employed to calculate the item-factor loadings. The data collected from another 318 freshmen were analyzed using confirmatory factor analysis method (CFA). Results: The scale contained 3 dimensions and 9 items with all content validity index ≥0.8. The difficulty coefficient of 9 items was 1.18-2.43. The discriminative validity analysis showed that the difficulty index was 0.41-0.78, and the discrimination index was 0.38-0.64. Each of the remaining items had a statistically significant difference in the score value between the top 27% and lowest 27% of respondents (t>3, P<0.05). The item's Cronbach's α was 0.72-0.77, corrected item-total correlation was 0.33-0.60 and the overall α of the scale was 0.77. EFA indicated all item-factor loading were higher than 0.680, and the accumulated variance contribution of the 3 factors was 62.484%. Results of CFA showed that the overall fitness index of the model reached the fitness standard except for the χ2 value. There was no statistical significance in the total score of the scale and the scores of each item among groups with different demographic characteristics (P>0.05). Conclusions: The newly developed public health safety literacy scale had a good reliability,validity,stability and item constancy.It can be used in measurement of the public health and safety literacy of university freshmen.

Highly efficient polarization-entangled photon-pair generation in lithium niobate waveguides based on bound states in continuum.

Integrated optics provides a platform for the experimental implementation of highly complex and compact circuits for practical applications as well as for advances in the fundamental science of quantum optics. The lithium niobate (LN) waveguide is an important candidate for the construction of integrated optical circuits. Based on the bound state in the continuum (BIC) in a LN waveguide, we propose an efficient way to produce polarization-entangled photon pairs. The implementation of this method is simple and does not require the polarization process needed for periodically poled LN. The generation rate of the entangled photon pairs increases linearly with the length of the waveguide. For visible light, the generation efficiency can be improved by more than five orders of magnitude with waveguides having the length of only a few millimeters, compared with the corresponding case without BICs. The phenomena can appear in a very wide spectrum range from the visible to THz regions. This study is of great significance for the development of active integrated quantum chips in various wavelength ranges.

Impact of insulin use on outcomes of diabetic breast cancer patients: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to assess the impact of insulin use on outcomes of breast cancer patients with diabetes mellitus (DM). MATERIALS AND METHODS: Databases of PubMed, Embase, and CENTRAL were searched to identify all types of studies comparing mortality or recurrence between insulin and non-insulin DM patients with breast cancer. Adjusted hazard ratios (HR) were pooled for a meta-analysis. RESULTS: Eleven studies were included. Meta-analysis indicated a statistically significant increased risk of all-cause mortality in insulin users as compared to non-users (HR: 1.52 95% CI: 1.23 to 1.86 I2=83% p<0.0001). Our results also demonstrated a statistically significant increase in the risk of breast cancer mortality amongst insulin users as compared to non-users (HR: 1.33 95% CI: 1.08 to 1.63 I2=43% p=0.007). Only four studies assessed the impact of insulin therapy on recurrence rates. Meta-analysis indicated a statistically significant increased risk of breast cancer recurrence in insulin users vs. non-users (HR: 1.43 95% CI: 1.13 to 1.80 I2=0% p=0.003). Mortality results were stable on sensitivity analysis. CONCLUSIONS: Diabetic breast cancer patients on insulin have increased mortality and recurrence rates as compared to insulin non-users. Owing to the several limitations of the review, results should be interpreted with caution. Future studies should assess the impact of timing, duration, dosage, and type of insulin therapy on clinical outcomes.

[Adrenocortical oncocytic tumors: a clinicopathological analysis of 44 cases].

Objective: To study the clinicopathological features of adrenocortical oncocytic tumors (ACOT) and to compare the diagnostic values of Lin-Weiss-Bisceglia (LWB) score and Helsinki score. Methods: Forty-four cases of ACOT diagnosed at Beijing Friendship Hospital, China from March 2008 to July 2019 were histologically analyzed to evaluate their malignant potential (benign versus malignant) according to two scoring criteria. Immunohistochemical studies (EnVision method) were also used. Results: There were 23 males and 21 females with an average age of 46 years. Histologically, the tumor cells were arranged in trabecular, chrysanthemum-shaped, glandular and microcapsule structures, while clear cells were rare or absent. Most of the tumor cells were moderately atypical, and intranuclear inclusion bodies were conspicuous. Immunohistochemical staining showed that tumor cells were positive for Melan A, inhibin, Syn and calretinin. The average proliferation index was 3% in benign ACOT, about 5% in ACOT of malignant potential, and>20% in malignant ACOT. According to the LWB score, 61.4% (27/44) of the tumors were on the left side and had multiple lesions. The percentage of benign ACOT was 59.1% (26/44), malignant potential 6.8% (3/44), malignant 34.1% (15/44), respectively. Among the 15 malignant ACOT, the mitotic figures>5/50 HPF were found in 13 cases, necrosis in 11 cases and capsule invasion in 10 cases. According to the Helsinki score, 65.9% (29/44) of the tumors were benign, and 34.1% (15/44) were malignant. There was no significant difference between the two scoring standards (P>0.05). During the follow-up of 9 to 144 months, 31 patients survived without disease and 13 patients relapsed or had metastasis. Conclusions: ACOT more likely be benign than malignant. The left side is more common. Malignant tumors are prone to recurrence and metastasis. The morphological parameters (high mitotic index, necrosis, and capsular invasion) in the LWB scoring standards combined with immunohistochemical parameters (Ki-67) in the Helsinki score are helpful for the diagnosis of malignant ACOT and are important predictors of poor prognosis.

[Correlation analysis between serum ferritin level and liver damage in acute stage of dengue fever].

Objective: To investigate the correlation between serum ferritin (SF) level and liver damage in the acute stage of dengue fever. Methods: A retrospective study was conducted to analyze 171 cases diagnosed with dengue fever as dengue fever group and 130 healthy patients as control group in Hangzhou 3A grade hospital from July to December 2017. Clinical data, SF and liver function related indicators were collected from both groups: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) to analyze the correlation between liver damage and SF in patients with dengue fever. Results: ALT, AST, and SF levels were significantly higher in the dengue fever group than those in the healthy control group (Z = 11.553, 15.054 and 15.163, P < 0.001). SF levels were higher in the dengue fever combined with liver damage group than those without the liver damage group (z = 6.930, P < 0.001). However, there was no statistically significant differences in age, gender, peak body temperature, and history of liver disease (P > 0.05). In addition, Spearman's correlation analysis showed that SF was positively correlated with ALT, AST, and TBIL (r = 0.464, 0.531 and 0.315, P < 0.001). Among dengue patients with different SF levels, there were significant difference in ALT, AST levels and incidence of liver damage (H = 14.240 and 17.584, χ(2) = 49.547, P < 0.001). Patients with higher SF levels had higher ALT, AST levels and incidence of liver damage. Binary logistic regression analysis showed that hyperferritinemia (SF≥500 ng/ml) was the risk factor for dengue fever combined with liver damage (OR = 8.120, P < 0.001). Furthermore, ROC curve analysis showed that the AUC for SF to judge dengue fever combined liver damage was 0.846 (95% CI: 0.785-0.908), and the sensitivity and specificity when the SF cut-off value was 1 506 ng/ml were 74.8% and 83.3%. Conclusion: There is a certain correlation between the SF level and the degree of liver damage in acute stage of dengue fever patients, and hyperferritinemia is a risk factor for dengue fever combined with liver damage.

[Anti-PD-1 therapy in advanced malignant liver tumor-induced type-1 diabetes mellitus: a case report].

Immune checkpoint inhibitor (ICI) has been emerged as a major breakthrough in tumor immunotherapy, but its unique mechanism of action has also led to a number of immune-related adverse events (irAE). Type 1 diabetes mellitus (T1DM) is one of the rarest irAEs. This paper reports a case of advanced malignant liver tumor-induced T1DM who received second-line anti-PD-1 therapy and showed initial symptoms of hyperosmolar coma and hyperglycemia. In addition, the relevant literature at home and abroad was collected and reviewed, and the clinical characteristics of T1DM induced by anti-PD-1 therapy were summarized with a view to achieve early detection, diagnosis and treatment.

Strong terahertz magneto-optical phenomena based on quasi-bound states in the continuum and Fano resonances.

We propose new ways to produce strong terahertz (THz) magneto-optical phenomena from monolayer graphene based on bound states in the continuum (BICs) and Fano resonances. The BICs and Fano resonances of radiation modes in the monolayer graphene are realized by designing the photonic crystal slab-graphene-slab structure. Based on them, the magnetic circular dichroism near 100% has been achieved. Importantly, such magneto-optical phenomena can be modulated in intensity and frequency using only electrostatic doping at a fixed magnetic field. Comparing two ways to produce magneto-optical phenomena, it is found that the way based on BICs exhibits some advantages such as good electrical tenability due to narrower resonance width, higher conversion efficiency and more stability with the change of incident angle. These phenomena can appear in a broad THz range by designing the nanostructures, which are very beneficial to polarization conversion and optoelectronic devices.

[Relationship of TLR2 and TLR4 expressions on the surface of peripheral blood mononuclear cells to small intestinal bacteria overgrowth in patients with hepatocellular carcinoma].

Objective: To investigate TLR2 and TLR4 expressional situation on the surface of peripheral blood mononuclear cells (PBMC) in patients with hepatocellular carcinoma (HCC) and their relationship with small intestinal bacterial overgrowth (SIBO). Methods: Flow cytometry was used to detect TLR2 and TLR4 expressional situation on the surface of PBMC in 78 cases with HCC, 56 cases with cirrhosis and 33 healthy controls. Furthermore, lactose hydrogen breath test (LHBT) was used to detect small intestinal bacterial overgrowth. Results: Of the 78 cases with HCC, 56 cases (71.8%) were SIBO-positive, 23 cases (41.1%) were SIBO- positive in 56 cases with cirrhosis, and 1 (3.0%) was SIBO-positive in 33 healthy controls. The incidence of SIBO in HCC patients was higher than cirrhosis patients (χ(2) = 12.72, P < 0.05) and healthy controls (χ(2) = 41.18, P < 0.05). The expression levels of TLR2 and TLR4 in HCC patients (100.55 ± 24.22, 42.76 ± 15.96) were significantly higher than cirrhosis (67.42 ± 18.36, 24.38 ± 8.68)and healthy control group (33.06 ± 11.72, 12.52 ± 4.46) (P < 0.05). Furthermore, the expression levels of TLR2 and TLR4 in SIBO-positive patients (108.75 ± 20.40, 48.1 ± 14.98) were higher than SIBO-negative patients (79.67 ± 20.60, 28.62 ± 7.36) (P < 0.05). Conclusion: The expression of TLR2 and TLR4 and the incidence of SIBO in HCC patients are significantly higher than cirrhosis and healthy control group. Moreover, the high expressions of TLR2 and TLR4 in SIBO-positive HCC patients may promote the development of HCC.