Objective To investigate the difference of facial soft tissue changes in patients with different vertical bone facial types after orthodontic treatment.Methods A total of 137 female patients with class Ⅱ malocclusion aged 18 to 30 years old were selected for retrospective analysis using facial soft tissue 3D model data.According to the mandibular plane angle(FH-MP)angle,they were divided into high angle group,average angle group and low angle group.The EinScan Pro 2X 2020 handheld high-precision 3D scanner was used to capture facial soft tissue images of patients before treatment(T0)and at 6 months during treatment(T1)and after treatment(T2).The patients'facial images were overlapped using reverse engineering software Geomagic Wrap 2021,and the differ-ences within and between groups were statistically analyzed using SPSS 26.0 statistical software.Results Before and after orthodontic treatment,the average overall facial changes in the high angle group were(-3.25±0.22)mm,in the average angle group was(-3.28±0.30)mm,and in the average low angle group was(-3.69±0.36)mm.Compared with the other two groups,the changes in the low angle group decreased more,and the difference was statistically significant(P＜0.05).The mandibular angle area and temporal area decreased the most in the low angle group,which were(-2.78±0.18)mm and(-2.27±0.35)mm,respectively,and the differ-ence was statistically significant compared with the other two groups(P＜0.05),while there was no statistically significant difference among the other groups(P＞0.05).Conclusion The whole face and all facial regions of the three groups had some negative changes,but the collapse in the mandibular angle area and the temporal muscle ar-ea of the low angle group was more obvious than that of the other two groups.

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

Objective:To evaluate the clinical efficacy of channel screw guided by O-arm navigation for the treatment of type II fragile fracture of pelvis (FFP) in the elderly.Methods:A retrospective cohort analysis was performed on clinical data of 37 patients with type II FFP admitted to Shanghai Pudong Hospital, Fudan University Pudong Medical Center from September 2019 to April 2021. There were 9 males and 28 females, aged 65-82 years [(71.8±10.1)years]. A total of 15 patients receipt channel screw fixation under O-arm navigation (surgical group) and 22 patients were treated conservatively (non-surgical group). The visual analogue scale (VAS) and Majeed functional score were compared between the two groups at emergency visit and at 1 week, 1 month, 3 months, 6 months after treatment. The accuracy of screw insertion and complications were also recorded during treatment and follow-up.Results:All patients were followed up for 6-18 months [(13.2±5.1)months]. There were no significant differences in the VAS and Majeed functional score between the two groups at emergency visit (all P>0.05). In both groups, lower VAS and higher Majeed functional score were found at 6 month after treatment as compared with those at emergency visit (all P<0.01). The VAS in surgical group was 2(1, 4)points at 1 week after treatment, lower than 4(3, 5)points in non-surgical group ( P<0.01). The VAS in surgical group was 1(1, 2)points at 1 month after treatment, lower than 3(2, 5)points in non-surgical group ( P<0.05). The Majeed functional score in surgical group was (50.2±4.2)points at 1 week after treatment, higher than (40.2±5.6)points in non-surgical group ( P<0.01). The Majeed functional score in surgical group was (73.8±5.2)points at 1 month after treatment, higher than (62.4±5.0)points in non-surgical group ( P<0.01). The two groups had no significant differences in VAS and Majeed functional score at 3 months and 6 months after treatment (all P>0.05). The accuracy of screw insertion in surgical group was 93% (14/15). In surgical group, the complication rate was 13%(2/15), including urinary tract infection in 1 patient and intraoperative screw penetration in 1, with no screw loosening or nerve and vascular injuries. In non-surgical group, the complication rate was 50%(11/22), including urinary tract infection in 5 patients, penetrating pneumonia in 5 and deep vein thrombosis in 1. The complication rate was significantly different between the two groups ( P<0.05). Conclusions:Compared with non-surgical treatment, the channel screw insertion guided by O-arm navigation can achieve precise screw placement, relieve pain early, promote functional recovery, realize accurate insertion of the screw and reduce the complication rate for type II FFP in the elderly.

Objective:To analyze the characteristics of COVID-19 case spectrum and spread intensity in different provinces in China except Hubei province.Methods:The daily incidence data and case information of COVID-19 were collected from the official websites of provincial and municipal health commissions. The morbidity rate, severity rate, case-fatality rate, and spread ratio of COVID-19 were calculated.Results:As of 20 March, 2020, a total of 12 941 cases of COVID-19 had been conformed, including 116 deaths, and the average morbidity rate, severity rate and case-fatality rate were 0.97/100 000, 13.5 % and 0.90 %, respectively. The morbidity rates in Zhejiang (2.12/100 000), Jiangxi (2.01/100 000) and Beijing (1.93/100 000) ranked top three. The characteristics of COVID-19 case spectrum varied from province to province. The first three provinces (autonomous region, municipality) with high severity rates were Tianjin (45.6 %), Xinjiang (35.5 %) and Heilongjiang (29.5 %). The case-fatality rate was highest in Xinjiang (3.95 %), followed by Hainan (3.57 %) and Heilongjiang (2.70 %). The average spread ratio was 0.98 and the spread intensity varied from province to province. Tibet had the lowest spread ratio (0), followed by Qinghai (0.20) and Guangdong (0.23). Conclusion:The intervention measures were effective in preventing the spread of COVID-19 and improved treatment effect in China. However, there were significant differences among different regions in severity, case-fatality rate and spread ratio.

Objective To investigate the gender differences and psychological influencing factors for anal rectal function in senile patients with functional constipation (FC) .Methods The gender differences and correlation of anal rectal function and psychological factors were compared in elderly patients and control group by anorectal manometry and psychological testing methods .Results The anal pressure drops of analog defecation of elderly female and male patients were attenuated and the rectal sensation thresholds increased compared with that of control group ,and the maximal squeezing pressure ,the rectal defecation pressure and anorectal pressure difference of elderly female patients were attenuated compared with that of elderly male patients .The SAS and SDS stand‐ard score of elderly female and male patients were significantly higher than that of control group .The SAS standard score of elderly female patients were higher than elderly male patients .SAS and SDS were negatively correlated with anorectal pressure difference and positively correlated with rectal first sensation volume (FSV) .Conclusion Anorectal dysfunction and psychological factors were involved in the elderly FC pathogenesy ,and they were related .Elderly female patients suffered more severe anxiety and anorectal motility disorders than male patients .

For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1 promoter activity was detected by Dual-Luciferase Reporter Assay System, it came that the relative luciferase activity of COL1A1 promoter was 15.98 times higher than that of control group induced by TGF-β1, showing the recombined plasmid could be used in cell model. The recombined plasmid was transfected into human hepatic stellate cells LX2, detected the effect of potential drugs, and obtained a stable expression system through stable transfection and monoclonal cell culture. A sample which could reduce COL1A1 promoter activity signally by our cell model, decreased collagen I mRNA and protein expression detected by real-time RT-PCR and Western blotting. It indicates this novel cell model can be used in high-throughput drug screening of potential anti-liver fibrosis drugs.