OBJECTIVES: To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. METHODS: Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. RESULTS: The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. CONCLUSIONS C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.
Animals ; Female ; Depression, Postpartum ; Complement C1q/metabolism* ; Antibodies, Neutralizing/pharmacology* ; Mice, Inbred C57BL ; Mice ; Hippocampus/metabolism* ; Pregnancy ; Disease Models, Animal

Background and Aims:Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation,specifically BRAFV600E,is a specific biomarker for papillary thyroid carcinoma (PTC). However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAFV600E mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAFV600E mutations were analyzed. Using postoperative pathology as the gold standard,the diagnostic performance of BRAFV600E mutation testing in FNA benign nodules was assessed. Results:Among the 84 FNA benign thyroid nodules,44 (52.4％) tested positive for the BRAFV600E mutation. Patients with BRAFV600E-positive nodules were more likely to be younger than 45 years (56.8％ vs. 35.0％,P=0.045),and their nodules had a smaller median long diameter compared to the BRAFV600E-negative group (0.49 cm vs. 0.61 cm,P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm,P=0.004) and a higher proportion of nodules<1 cm (95.2％ vs. 71.4％,P=0.007),with a higher BRAFV600E mutation rate (68.3％ vs. 4.8％,P<0.001). In terms of the ultrasound characteristics of thyroid nodules,BRAFV600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4％ vs. 60.0％,P=0.006). Similarly,PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0％ vs. 52.4％,P=0.010). Multivariate Logistic regression analysis indicated that BRAFV600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAFV600E-negative nodules (P=0.001),with BRAFV600E mutation being an independent risk factor for PTC diagnosis. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of BRAFV600E mutation testing for PTC diagnosis were 69.3％,95.2％,97.7％,50.0％,and 75.0％,respectively. Conclusion:BRAFV600E mutation testing demonstrates high positive predictive value and accuracy,and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAFV600E mutation testing.

Background and Aims:Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation,specifically BRAFV600E,is a specific biomarker for papillary thyroid carcinoma (PTC). However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAFV600E mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAFV600E mutations were analyzed. Using postoperative pathology as the gold standard,the diagnostic performance of BRAFV600E mutation testing in FNA benign nodules was assessed. Results:Among the 84 FNA benign thyroid nodules,44 (52.4％) tested positive for the BRAFV600E mutation. Patients with BRAFV600E-positive nodules were more likely to be younger than 45 years (56.8％ vs. 35.0％,P=0.045),and their nodules had a smaller median long diameter compared to the BRAFV600E-negative group (0.49 cm vs. 0.61 cm,P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm,P=0.004) and a higher proportion of nodules<1 cm (95.2％ vs. 71.4％,P=0.007),with a higher BRAFV600E mutation rate (68.3％ vs. 4.8％,P<0.001). In terms of the ultrasound characteristics of thyroid nodules,BRAFV600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4％ vs. 60.0％,P=0.006). Similarly,PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0％ vs. 52.4％,P=0.010). Multivariate Logistic regression analysis indicated that BRAFV600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAFV600E-negative nodules (P=0.001),with BRAFV600E mutation being an independent risk factor for PTC diagnosis. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of BRAFV600E mutation testing for PTC diagnosis were 69.3％,95.2％,97.7％,50.0％,and 75.0％,respectively. Conclusion:BRAFV600E mutation testing demonstrates high positive predictive value and accuracy,and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAFV600E mutation testing.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective:To identify the risk factors for acute kidney injury (AKI) after non-cardiac surgery.Methods:Medical records of patients who underwent non-cardiac surgery with general anesthesia in our hospital from October 1, 2016 to March 31, 2021 were collected.AKI was diagnosed using the Kidney Disease Improving Global Outcomes definition of AKI.Multi-factor logistic regression analysis was used to screen the risk factors affecting AKI.Generalized linear regression was used to analyze the factors influencing the difference in serum creatinine before and after surgery.Results:A total of 2 214 patients were eventually enrolled, and the incidence of AKI was 5.15%.The results of multi-factor logistic regression analysis showed that preoperative hypertension, American Society of Anesthesiologists Physical Status classification ≥ Ⅲ, intraoperative bleeding >300 ml, emergency surgery, and grade IV surgery were independent risk factors for AKI after non-cardiac surgery ( P<0.05). The results of generalized line regression analysis showed that preoperative hyponatremia, intraoperative bleeding >300 ml, emergency surgery, and duration of anesthesia were positively correlated with increased difference in serum creatinine before and after surgery ( P<0.05). Conclusions:Preoperative hypertension, American Society of Anesthesiologists Physical Status classification ≥ Ⅲ, intraoperative bleeding >300 ml, emergency surgery and grade IV surgery are independent risk factors for AKI after non-cardiac surgery.

Objective:To explore the safety and feasibility of Da Vinci robotic-assisted laparoscopic resection in treatment of liver benign tumors.Methods:The clinical data of 62 patients with liver benign tumors admitted to Fujian Medical University Union Hospital from January 2016 to December 2019 were retrospectively analyzed. All patients were divided into 2 groups: 25 cases undergoing Da Vinci robotic-assisted laparoscopic resection (the robotic group) and 37 cases undergoing conventional laparoscopic resection for liver benign tumors (the laparoscopic group). The operation duration, intraoperative blood loss, postoperative abdominal drainage tube removal time, incidence of postoperative complications, postoperative hospital stay time of both groups were compared.Results:Operations of all 62 patients were successfully completed. The operation time of the robotic group was longer than that of the laparoscopic group [(192±52) min vs. (158±41) min], intraoperative blood loss of the robotic group was less than that of the laparoscopic group [(159±67) ml vs.(213±59) ml], and differences were statistically significant between the two groups (both P < 0.05). The postoperative abdominal drainage tube removal time of the robotic group and the laparoscopic group was (7.0±1.5) d and (7.2±1.3) d, the incidence of postoperative complications was 8.0% (2/25) and 5.4% (2/37), and the postoperative hospital stay time was (7.0±2.4) d and (7.3±2.2) d, respectively; and differences were statistically significant between both groups (all P > 0.05). Conclusion:Da Vinci robotic-assisted laparoscopic resection is a safe and effective operation method in treatment of liver benign tumors with advantages of small wound and less blood loss.

Objective:To identify the pathogenic mutation in a patient with Oguchi disease.Methods:A Japanese patient with Oguchi disease was enrolled in this study, and underwent a comprehensive medical history assessment and multiple ophthalmic examinations, including BCVA, OCT, color fundus photography and full field electroretinogram. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood samples for whole exome sequencing. The gene mutation was detected, and the analysis software was used to determine the conservation of the mutation and the possible structural changes.Results:The patient, 71 years old, with consanguineous parents, complained of night blindness since early childhood. BCVA in both eyes was 0.7 and the golden-yellowish reflex appeared in the grey retina. The scotopic 0.01 ERGs showed a extinguished reaction in both eyes. The scotopic 3.0 ERGs showed a "negative" configuration with a significantly reduced a wave and a nearly absent b wave. A homozygous deletion mutation in the SAG gene (c.924delA, p.N309Tfs*12) in this patient was founded by DNA sequencing, which was predicted to generate prematurely truncated SAG protein and result in severe structural change. Homology analysis of the protein sequence indicated that the mutation resulted in an altered amino acid which was evolutionarily highly conserved among different species, strongly suggesting the potential pathogenicity of this homozygous mutation.Conclusion:The mutation c.924delA(309Tfs*12) in SAG cause Oguchi disease in this patient.

Objective To evaluate the effectiveness of computer aided design (CAD) and three bit printing in the management of orthognathic surgery.Methods A total of 5 cases of patients with jaw deformity were involved in this study;jaw teeth and CT scanning laser scanning hefore surgery,virtual surgery design of 3D reconstruction and fusion data were analyzed,according to the design scheme of double jaw surgery combined with genioplasty;design and 3D printing of maxillary Le Fort Ⅰ osteotomy,genioplasty titanium alloy resin osteotomy and positioning guide,sagittal split ramus osteotomy by 3D printing and plate technology were used in this approach.The postoperative results were compared with the surgical planning by three-dimensional measurement and statistical analysis.Results When the operation guide plate was applied smoothly,the maximum error for maxilla was 1.2 mm (0.3-1.2 mm),and the maximum error for genioplasty was 1.7 mm,(0.5-1.7 mm),and the mean error was less than 1 mm.Follow-up for 12 months showed no adverse reaction.Conclusions Three dimensional printing surgical guide plate can accurately provide the osteotomy information,effectively control the jaw movement,and improve the orthognathic surgery accuracy of patients with partial jaw deformity.

Objective To identify the factors those regulate CCCP-induced non-canonical autophagy.Methods Different cells expressing GFP-LC3 were treated with or without CCCP (30μM) for 6 h.Fluorescent images were taken and cell lysates were analyzed by western blot assay.Real-time PCR was used to measure the mRNA levels of LC3B.FIP200-KO MEF cells were cultured and treated by 30 μM CCCP with or without water channel inhibitors, for 6 h.Cell lysates were analyzed by Western blot assay.Results CCCP could not induced autophagy in Atg5-KO MEF cells.CCCP could induce non-canonical autophagy in ULK1-KO MEF, FIP200-KO MEF, and Beclin1-KD U251.CCCP treatment in FIP200-KO MEF cells had no effect on the expression level of LC3B mRNA.We also found two distinct aquaporin water channel inhibitors could inhibit the generation of LC3 which was induced by CCCP.Conclusion CCCP induced non-canonical autophagy was Atg5-dependent, but Beclin1-, ULK1-and FIP200-independent.Osmotic imbalance could regulate CCCP-induce non-canonical autophagy.

ObjectiveTo investigate the effect of NOTCH4 expression on vasculogenic mimicry (VM) formation in hepatocellular carcinoma (HCC). MethodsTumor tissues were collected from 85 patients diagnosed with HCC. The relationship between NOTCH4 expression and VM was examined using immunohistochemical staining and PAS/CD31 double staining. The influence of siRNA-mediated NOTCH4 silencing on VM network formation in HCC was observed in the 3D cell culture system in vitro. Experimental data were assessed with Mann-Whitney U test and one-way analysis of variance. ResultsNOTCH4 had significantly higher expression in VM-positive HCC tissues than in VM-negative HCC tissues (P=0.019). In siRNA-treated cells, NOTCH4 mRNA and protein expression was significantly down-regulated compared with those in mock-treated cells (P=0.007; P=0.003) and untreated cells (P=0.000; P=0.000). VM network formation was impaired by inhibition of NOTCH4 expression in the 3D cell culture system. ConclusionNOTCH4 plays an important role in VM formation in HCC and may provide a novel molecular target for anti-angiogenesis therapy for HCC.