Objective: : Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. Methods: : The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. Results: : A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin scale, 0–2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. Conclusion : In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Animals ; Dopaminergic Neurons/physiology* ; GABAergic Neurons/physiology* ; Mice ; Nucleus Accumbens/metabolism* ; Reward ; Ventral Tegmental Area/metabolism*

Hematopoietic progenitor kinase 1 ( HPK1 ) , also known as MAP4K1 , is a serine/threonine protein kinase and a member of the MAP4K family of mammalian Ste20-related pro¬tein kinases.Recent studies have found that HPK1 is assoeiated with the occurrence and progression of a variety of tumors, and may play an important role in some malignant tumors.This pa¬ per reviews the HPK1 signaling pathway, its relationship with tumor and drug development progress, so as to provide referenee for the research of HPK1 protein kinase.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective:To explore the feasibility and clinical value of artificial intelligence-assisted breast ultrasound in screening breast cancer in Tibet.Methods:Two hundred and eighty-six women who participated in breast cancer screening in Shigatse People′s Hospital from August to September in 2021 were selected. The study included four groups. Group 1, ultrasound screening by senior breast ultrasound doctors from Shanghai; Group 2: local ultrasound doctors used intelligent-assisted ultrasound equipment for screening; Group 3: local ultrasound technicians used intelligent-assisted ultrasound equipment for screening; Group 4: ultrasound screening by local ultrasound doctors. The pathological results of screening positive cases and six-month ultrasound follow-up results of negative cases were set as the gold standard.Results:Twenty-seven lesions of 21 persons were screened positive. Pathology showed that 1 case of invasive ductal carcinoma, 1 case of severe atypical hyperplasia, 6 cases of fibroadenoma, 5 cases of breast disease, 14 cases of breast hyperplasia. Two hundred and sixty-five persons were screened negative, and the results of the six-month ultrasound follow-up were still negative. The accuracy, sensitivity, and specificity of group 2 were 0.966, 1, and 0.964 respectively; The accuracy, sensitivity, and specificity of group 3 were 0.935, 0.769, and 0.943 respectively; The accuracy, sensitivity, and specificity of group 4 were 0.860, 0.308 and 0.885 respectively. The accuracy and area under the curve of groups 2 and 3 were significantly different from that of group 4 (all P<0.001), and there was no significant difference from that of group 1 ( P=0.063, P=0.055). Conclusions:Artificial intelligence-assisted breast ultrasound screening technology can effectively improve the screening efficiency of non-breast ultrasound specialists and technicians. It is very suitable to solve the problems faced by grass-roots screening in Tibet and has great social significance and clinical value.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Aim To establish three kinds of DNA damage models of mouse testicular spermatogonia cell line GC-1 cells and analyze their similarities and differences. Methods GC-1 cells were treated with UVB irradiation, D-galactose(D-Gal) or bleomycin (BLM), respectively. Then the expression and localization of 'Y-H2AX were detected by Western blot and immunofluorescence, the expression and localization of 8-OHdG were measured by immunofluorescence, and the expression levels of p-p53 and p21 were measured by Western blot. Results The expression of -y-H2AX in GC-1 cell reached to the peak 4 h after UVB irradiation and 6 h after D-Gal stimulation, whereas -y-H2AX expression gradually increased after BLM stimulation, and the higher the concentration of BLM,the shorter the time to reach the peak. The results of immunofluorescence showed that 8-OHdG expression was observed in the nucleus and cytoplasm of GC-1 cells after UVB irradiation and BLM stimulation, and the longer the culture time, the more the expression in the nucleus. In contrast, the expression of 8-OHdG was observed in the cytoplasm and reached the peak at 6 h in the D-Gal stimulated GC-1 cells. After UVB irradiation, the protein expression levels of p-p53 gradually increased, while p21 protein expression appeared later than that of p-p53; in the D-Gal stimulated GC-1 cells, the protein expression levels of p-p53 reached the peak at 6 h, and p21 protein expression reached the peak at 12 h; after low concentration BLM stimulation, the protein expression levels of p-p53 and p21 continuously increased, and after high concentration BLM stimulation, the protein expression levels of p-p53 and p21 reached its peak at 2 h, then decreased at 4 h. Conclusions Three kinds of DNA damage models of GC-1 cells are successfully established, and the DNA damage in GC-1 cells treated with D-Gal is mild, while the DNA damage in GC-1 cells treated by UVB irradiation and BLM stimulation is more severe.

Objective:To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants.Methods:In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31 +6 weeks) and moderate to late preterm (32-36 +6 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2′-fucosyllactose (2′FL) concentration in colostrum and transitional milk greater than 200 μg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher′s exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. Results:79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ2=1.31, P>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 μg/mL, respectively (Kruskal-Wallis χ2=8.1234, P=0.044). When analyzed by the median weight gain of the infants (low vs high weight gain) at 4 months postpartum, 2′FL was significantly lower in the high weight gain group at 7 d (1 818.04 μg/mL vs 2 181.67 μg/mL, W=1 386, P=0.018), while LNT & LNnT were significantly higher (1 182.36 μg/mL vs 1 053.62 μg/mL, W=816, P=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 μg/mL vs 286.18 μg/mL, W=564, P=0.026). Conclusions:The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.