Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.

Objective:To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS).Methods:A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard.Results:Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234).Conclusions:The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

Objective:To analyze the trend of maternal mortality ratio (MMR) and death causes in Tianjin from 2011 to 2020 and to guide the management of maternal health.Methods:All the reviews data of 89 maternal death cases in Tianjin from 2011 to 2020 were retrospectively collected to analyze the trend of MMR, rank order of death causes, and death review results using Chi-square test. Results:(1) The average MMR in Tianjin was 7.97/100 000 during the study period, showing an overall fluctuating decline. The highest MMR was 12.61/100 000 in 2014 and the lowest was 3.85/100 000 in 2019. (2) Among the dead pregnant women and parturients, non-registered residents had higher proportion of women with advanced age, no steady occupation/unemployment, below junior college education, multipara, or without maternal health manual compared with the registered residents [33.33% (8/24) vs 20.00% (13/65), χ2=46.18; 100.00%(24/24) vs 69.23%(45/65), χ2=9.53; 87.50% (21/24) vs 64.62% (42/65), χ2=4.44; 79.17% (19/24) vs 44.62% (29/65), χ2=8.42; 75.00%(18/24) vs 13.85% (9/65), χ2=31.02; all P<0.05]. (3) Direct obstetric factors and indirect factors that caused death were accounted for 57.30% (51/89) and 42.70% (38/89). The top five death causes were postpartum hemorrhage, hypertensive disease during pregnancy, sudden death, venous thrombosis and pulmonary embolism, and amniotic fluid embolism. (4) In terms of the maternal death review results, 39.33% (35/89) of maternal deaths were avoidable, among which 94.29% (33/35) were caused by direct obstetric factors and 5.71% (2/35) were indirect. (5) The main influencing factors of avoidable death causes were knowledge and skills inadequacy in the health care system (62.86%, 22/35), of which 86.36% (19/22) happened in health facilities at and below the district/county level. Conclusion:It is suggested to strengthen the medical care of health facilities at and below the district/county level and the maternal health management of the non-permanent residents to ensure maternal and infant safety and to further reduce the MMR.

BACKGROUND: Mesenchymal stem cells (MSCs) have strong self-renewal ability and multiple differentiation potential. Some studies confirmed that spreading shape and area of single MSCs influence cell differentiation, but few studies focused on the effect of the circularity of cell shape on the osteogenic differentiation of MSCs with a confined area during osteogenic process.METHODS: In the present study, MSCs were seeded on a micropatterned island with a spreading area lower than that of a freely spreading area. The patterns had circularities of 1.0 or 0.4, respectively, and areas of 314, 628, or 1256 µm² . After the cells were grown on a micropatterned surface for 1 or 3 days, cell apoptosis and F-actin were stained and analyzed. In addition, the expression of β-catenin and three osteogenic differentiation markers were immunofluorescently stained and analyzed, respectively.RESULTS: Of these MSCs, the ones with star-like shapes and large areas promoted the expression of osteogenic differentiation markers and the survival of cells. The expression of F-actin and its cytosolic distribution or orientation also correlated with the spreading shape and area. When actin polymerization was inhibited by cytochalasin D, the shape-regulated differentiation and apoptosis of MSCs with the confined spreading area were abolished.CONCLUSION: This study demonstrated that a spreading shape of low circularity and a larger spreading area are beneficial to the survival and osteogenic differentiation of individual MSCs, which may be regulated through the cytosolic expression and distribution of F-actin.
Actins ; Antigens, Differentiation ; Apoptosis ; Cell Differentiation ; Cell Shape ; Cytochalasin D ; Cytosol ; Mesenchymal Stromal Cells ; Osteogenesis ; Polymerization ; Polymers

Objective To study the effects of fat grafting on partial jaw deformity.Methods A total of 19 cases of partial jaw deformity.were used fat grafting in past 2.5 years,from January 2012 to June 2015.All analyses were to find suitable fat grafting method for partial jaw deformiw.Fat graft was obtained by low pressure suction and low speed centrifugation.Results A lot of 15 patients in this group had been followed up for 6 months to 2 years.9 patients was satisfied with once fat grafting and 6 with twice.Conclusions Fat grafting provides a useful alternative to partial jaw deformity with normal occlusion.But it also remains to be seen what the forward effects of fat grafting on partial jaw deformity are.

Some problems are arisen in teaching diagnostic pathology in our college for postgradu-ates of Pathology and Pathophysiology, the students' basic knowledge is weak, the cycle is short, the teaching team and resources are relatively insufficient. To promote the cultivation of graduate students, we should carry out the CBL teaching method, add the clinical practice and training, strengthen the teaching staff, and apply digital section and network platform.

Hepatitis B virus (HBV) infection is a worldwide health problem and vertical transmission is the main source of chronic infection in Asian countries. Breakthrough perinatal HBV transmission occurs in 10%-15% of infants born to pregnatal women with high viral load even with appropriate postexposure immunoprophylaxis. Management of chronic hepati?tis B (CHB) during pregnancy remains a challenge, with unique issues that involve prevention of mother-to-child transmis?sion (MTCT) and safe use of antiviral therapy. Previous studies indicate that antiviral therapy with analogs (Lamivudine, Tel?bivudine or Tenofovir) may prevent vertical transmission during late pregnancy in highly viremic mothers. This article sum?marized relevant studies that antiviral therapy in preventing MTCT of hepatitis B virus.

Objective To summary the echocardiographie features of the patients with dissection into interventricular septum (IVS) and to analyze the etiology.Methods The data of 13 cases with the dissection into the interventricular septum diagnosed by echocardiography were reviewed to summarize the echocardiographic features and the analysis of etiology.Results Among the 13 patients with dissection into IVS,11 patients were dissected into IVS from the right sinus of Valsalva (SOV),in which 5 patients were from single aneurysm of the right SOV,one patient was from a combination of a bicuspid aortic valve and right SOV,4 patients were from aortic valve infection of infective endocarditis,and one patient was induced by severe paravalvular leak after mechanical aortic valve prosthetic replacement was complicated by annular detachment.In all 11 patients,eehocardiography showed a dissecting cystic-like mass in the IVS from the base to mid septum or confined to the septal base.The path of the dissection in all these patients was traced to the right SOV.In the other 2 patients,IVS dissection followed septum rupture due to a myocardial infarction.Conclusions Echocardiography could accurately diagnose dissections of the IVS and to analyze the etiology,which is very helpful to make the clinical medical strategy.

Objective To investigate the effects of local mild hypothermia on the expression of EMAP-Ⅱ and proEMAP-Ⅱ after cerebral ischemia and reperfusion in rats and to explore the possible neuroprotection mechanism of mild hypothermia.Methods Forty-four male Wistar rats were divided randomly into a sham-operation group (Sham),a normothermia group (NT) and a hypothermia group (HT).Middle cerebral artery occlusion was performed using Longa's method,and reperfusion was allowed after 2 hours of occlusion.Mild hypothermia (33.0 ± 0.5)℃ for 6 hours was initiated at the start of reperfusion,followed by rewarming.Brains were harvested after 6,12,24,48 and 72 hours of reperfusion and used for HE staining to evaluate cellular apzoptosis and immunohistochemical staining for detecting the expression EMAP-Ⅱ and proEMAP-Ⅱ.Results The expression of EMAP-Ⅱ and proEMAP-Ⅱ in the ischemic penumbra was significant at 6 hours in the normothermia and hypothermia groups.It peaked at 12 hours in the normothermia group and 24 hours in the hypothermia group,and then decreased gradually.At 72 hours the expression of EMAP-Ⅱ and proEMAP-Ⅱ in the ischemic penumbras was very close to that in the sham group.EMAP-Ⅱ-positive cells were significantly fewer in the hypothermia group than in the normothermia group at all time points.ProEMAP-Ⅱ-positive cells were significantly more numerous in the normothermia group than in the hypothermia group at 6,12 and 24 hours.Conclusions Mild hypothermia (33.0 ± 0.5) ℃ has a valid neuroprotective effect which involves reducing EMAP-Ⅱ and proEMAP-Ⅱ expression in the ischemic penumbra and inhibiting apoptosis and inflammatory reactions after cerebral ischemia and reperfusion,at least in rats.