Objective:To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice.Methods:The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3.Results:The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) μm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) μm) of mice in T45 group and T60 group was significantly increased ( P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group ( P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group ( P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions:Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.

Objective To conduct a scoping review of studies on the use of virtual reality(VR)in cancer-related cognitive impairment(CRCI),and to generalize and summarize the current state of the art of VR use in CRCI.Methods The computerized retrieval of PubMed,Embase,Web of Science,the Cochrane Library,WanFang Data,CNKI and VIP databases was carried out.Studies were collected from the database establishment to July 2023.3 researchers independently screened the literature,extracted data,and evaluated the risk of bias in the included studies.Results A total of 9 studies were included.VR was used for CRCI assessment and intervention.The assessment included visual and auditory memory,executive function and verbal fluency.The intervention content involved common cognitive impairment dimensions of CRCI,including memory,executive ability,attention,information processing speed and language fluency.The intervention frequency ranged from 3 to 5 times/week,15 to 60 min/time,and the duration was 2 to 8 weeks.The intervention frequency and intensity were dynamically adjusted based on the patient performance,game type and complexity.VR has shown good validity and benefits in CRCI assessments and interventions,while improving patients'sleep quality and ability to perform daily living,with higher patient acceptance and no VR related adverse events being reported,but its role in improving mental health remains controversial.Conclusion VR shows good validity and benefits in CRCI assessment and intervention,and has good safety and high acceptance.In the future,it is still necessary to conduct large-sample,randomized controlled studies,attach importance to the role of patient needs in the formulation of VR cognitive intervention programs,and increase CRCI-related objective indicators to further verify the effect of VR intervention on CRCI.At the same time,longitudinal evaluation and follow-up programs may be considered to determine progressive changes in CRCI from VR interventions.

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10 8/kg, and the number of CD34 + cells was 3.29 (2.53-6.10) ×10 6/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA). Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively). Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

Objective To investigate the high risk factors of endometrial polyps (EPs)in infertile patients and its impact on the pregnancy outcome after embryo transfer.Methods A case-control trail was conducted on the infertility patients who undergoing embryo transfer in our hospital for the first time after hysteroscopy from January 2016 to December 2022.Their clinical data were collected and retrospectively analyzed.Univariate and stepwise logistic regression analyses were used to identify the risk factors for EPs,and the impact of polyps on the pregnancy outcomes of assisted reproductive pregnancy was analyzed with propensity score matching (PSM)at a 1:2 ratio.Results A total of 388 patients diagnosed with Eps and undergoing hysteroscopic endometrial polypectomy were assigned into the Eps group,and 2163 non-polyp patients were into the non-Eps group.Univariate analysis showed statistical differences were observed in age[31 (29,34)vs 31 (28,33),P=0.002],history of pelvic inflammatory disease (42.78％vs 64.17％,P=0.000),age at menarche[14 (12,14)vs 13 (12,14)years old,P=0.000],number of pregnancies[0 (0,1 )vs 1 (0,2),P=0.000],primary infertility (60.30％vs 50.20％,P=0.000),duration of infertility[4 (2.1,6.0)vs 4 (2.0,6.0)years,P=0.002],concomitant endometriosis (9.53％ vs 6.52％,P=0.032),concomitant uterine fibroids (11 .85％vs 6.93％,P=0.001 ),and basal estrogen level[38.12 (27.00,59.00)vs 36.00 (25.00,53.00)μg/L,P=0.016]between the 2 groups.Logistic stepwise regression analysis indicated that age (OR=1 .082,95％CI:1 .053～1 .113,P<0.05 ),primary infertility (OR=2.951,95％CI:1 .990～4.376,P<0.05),and elevated basal estrogen (OR=1 .003,95％CI:1 .001～1 .005,P<0.05)were risk factors for Eps.The postoperative biochemical pregnancy rate (59.28％vs 52.70％),clinical pregnancy rate (53.09％vs 45.48％),and live birth rate (43.81％vs 35.82％)were significantly higher in the matched Eps group than the non-Eps group (P<0.05 ).No statistical difference was observed in pregnancy outcome in the patients with different polyp locations and sizes.The patients with multiple polyps had an obvious higher rate of early miscarriage than those with single polyp (17.27％ vs 7.29％,P<0.05 ),while those with recurrent polyps also had a higher rate of early miscarriage than those with primary polyps (27.78％vs 11.23％,P<0.05).Conclusion Age,primary infertility,and elevated basal estrogen are risk factors for Eps in infertility patients,while hysteroscopic endometrial polypectomy prior to embryo transfer results in improved pregnancy outcomes in those with Eps.The location and size of endometrial polyps have weak impact on pregnancy outcomes following embryo transfer,but,the presence of multiple or recurrent polyps may elevate the risk of early miscarriage.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective: To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion. Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns. Results : Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth. Conclusions The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

Ulcerative colitis （UC） is a chronic non-specific inflammatory disease characterized by the damage of the epithelial barrier of the colon and the destruction of immune homeostasis. It has a long course， no recovery and high recurrence rate， and is recognized as a difficult digestive disease. MicroRNA （miRNA） has been confirmed to be specifically or differentially expressed in both UC patients and UC animal models， so miRNA can be used as markers for UC diagnosis or reference for treatment evaluation. TCM therapy has a definite therapeutic effect， a wide range of effects， and minimal side effects in the treatment of UC， so this article takes miRNA as the starting point and systematically elaborates on the mechanism of TCM regulating UC related signaling pathways by regulating the expression of miRNA. The results show that chlorogenic acid， Anchang decoction， and Fuyang huoxue jiedu formula can regulate the expressions of miR-155， miR-146a and miR-31-5p， etc.， thereby inhibiting signal transducer and activator of transcription （STAT） signal pathway transduction to improve UC. Limonin， ginsenoside Rh2， artesunate， etc. can inhibit nuclear factor-κB （NF-κB） signaling pathway conduction to improve UC by regulating the expressions of miR-214， miR- 155 and miR-19a， etc. Nitidine chloride， berberine， resveratrol， etc. can regulate the expressions of miR-31， miR-146a， miR- 146b， etc.， thereby inhibiting the Toll-like receptor 4 （TLR4） signaling pathway to improve UC. Mango polyphenolics， Compound qinbai granules， and Astragalus membranaceus polysaccharides can regulate the expressions of miR-126 and miR-193a-3p， thereby inhibiting the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/AKT/mTOR） signaling pathway to improve UC.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.