This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel (abpaclitaxel) and anlotinib for ovarian cancer. In this study, 44 patients diagnosed with platinum-resistant ovarian cancer were enrolled. Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria. The primary endpoint was the investigator-evaluated objective response rate (ORR). 44 patients were enrolled between January 2021 and March 2023 with a median age of 49 years. Twenty-nine had measurable lesions and 15 had non-measurable lesions. Overall, the investigator-evaluated ORR was 56.8% (25/44; 95% CI 0.411-0.713) in intention-to-treat population and 58.1% (25/43; 95% CI 0.422-0.726) in per-protocol population. The median progression-free survival was 9.8 months, and the median duration of response was 7.4 months. For safety, grade 3/4 adverse events (AEs) included leukopenia, gum pain, hypertension, and hand-foot syndrome. The response rates were 55.0% (11/20) in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors. The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer. Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.
Humans ; Female ; Middle Aged ; Indoles/therapeutic use* ; Quinolines/therapeutic use* ; Carcinoma, Ovarian Epithelial/drug therapy* ; Adult ; Ovarian Neoplasms/drug therapy* ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Aged ; Drug Resistance, Neoplasm ; Albumin-Bound Paclitaxel/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival ; Paclitaxel/administration & dosage* ; Treatment Outcome

Digital simulation and three-dimensional (3D) printing technology-assisted treatment of mandibular fractures in children has good clinical application value. During the surgery, attention should be paid to the fixation of dentition defects, jawbone development, and the protection of permanent tooth germs. This article reports a case of a 7-year-old male patient with a mandibular chin fracture, treated with digital simulation of fracture reduction and 3D printing of mandible model, along with implantable occlusal splint, then underwent open reduction and internal fixation surgery. After 3 and 6 months, the 3D printed splint and internal fixation titanium plate were removed. The mandibular fracture healed well, without affecting jawbone development, and the tooth germs remained undamaged, the occlusal relationship recovered well. The case suggests the use of computer digital simulation and 3D printing technology facilitates precise reduction of mandibular fractures and reduces the impact on the jawbone and tooth germs, which provids valuable clinical reference.

BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5％ CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.

BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5％ CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.

Digital simulation and three-dimensional (3D) printing technology-assisted treatment of mandibular fractures in children has good clinical application value. During the surgery, attention should be paid to the fixation of dentition defects, jawbone development, and the protection of permanent tooth germs. This article reports a case of a 7-year-old male patient with a mandibular chin fracture, treated with digital simulation of fracture reduction and 3D printing of mandible model, along with implantable occlusal splint, then underwent open reduction and internal fixation surgery. After 3 and 6 months, the 3D printed splint and internal fixation titanium plate were removed. The mandibular fracture healed well, without affecting jawbone development, and the tooth germs remained undamaged, the occlusal relationship recovered well. The case suggests the use of computer digital simulation and 3D printing technology facilitates precise reduction of mandibular fractures and reduces the impact on the jawbone and tooth germs, which provids valuable clinical reference.

Objective:To investigate the effects of fluoride exposure on kidney injury in rats and the sirtuin 3 (SIRT3)-fork head protein O3a (FOXO3a)-tensin homolog induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (PARKIN) pathway.Methods:Twenty-four 4-week-old SD rats (clean grade, body mass 100 - 150 g) were selected and divided into three groups according to the randomized numeric table: control group, low fluoride group, and high fluoride group, with eight rats in each group (half male and half female). The control group was given free access to tap water (fluoride ion concentration < 0.5 mg/L), while the low fluoride and high fluoride groups were given free access to tap water and sodium fluoride solutions with fluoride ion concentrations of 5.0 and 50.0 mg/L, respectively, for a period of 180 days. The formation of dental fluorosis in rats was observed and recorded, and the femur, urine and blood samples of rats were collected to measure bone fluoride, urinary fluoride, and blood fluoride levels, and to detect kidney function related indicators (serum uric acid, creatinine, and urea nitrogen contents). Morphological changes of renal tissues stained with hematoxylin-eosin (HE) were observed under a light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of renal SIRT3, FOXO3a, PINK1, PARKIN, microtubule associated protein 1 light chain 3 (LC3), autophagy receptor protein (P62), respectively.Results:Seven and one rats in the low and high fluoride groups were found to haveⅠdegree dental fluorosis, while zero and seven rats were found to haveⅡdegree dental fluorosis. Compared with the control group, rats in the low and high fluoride groups had higher levels of bone fluoride (μg/g: 1.18 ± 0.06, 2.16 ± 0.07 vs 0.52 ± 0.05), urinary fluoride (mg/L: 4.43 ± 0.11, 7.46 ± 0.09 vs 2.58 ± 0.14), blood fluoride (μg/ml: 0.77 ± 0.06, 1.68 ± 0.10 vs 0.52 ± 0.08), serum uric acid (μg/ml: 61.01 ± 4.17, 103.92 ± 5.43 vs 28.68 ± 2.91), creatinine (μg/ml: 74.82 ± 9.61, 132.05 ± 5.35 vs 22.38 ± 4.11), and urea nitrogen (μg/ml: 13.36 ± 1.27, 14.55 ± 0.34 vs 0.29 ± 0.07, P < 0.05). Under the light microscope, the kidneys of the control group showed tight and orderly arrangement of renal tubules and glomerular cells, with complete and clear cell contours. The low fluoride group was similar to the control group and no significant abnormalities were observed. The high fluoride group showed abnormal glomerular structure and atrophy, with some areas of renal tubules showing epithelial cell edema and unclear intercellular boundaries. The results of qRT-PCR assay showed that compared with the control group, the low and high fluoride groups had lower mRNA expression levels of SIRT3 (0.82 ± 0.03, 0.58 ± 0.02 vs 1.00 ± 0.08), P62 (0.75 ± 0.07, 0.28 ± 0.09 vs 1.00 ± 0.07, P < 0.05), and higher mRNA expression levels of FOXO3a (1.35 ± 0.04, 3.01 ± 0.23 vs 1.00 ± 0.08), PINK1 (1.58 ± 0.09, 3.28 ± 0.09 vs 1.00 ± 0.07), PARKIN (1.51 ± 0.04, 1.67 ± 0.10 vs 1.00 ± 0.05), LC3 (1.74 ± 0.07, 2.38 ± 0.18 vs 1.00 ± 0.08, P < 0.05). The results of Western blotting showed that compared with the control group, the low and high fluoride groups had lower protein expression levels of SIRT3 (0.91 ± 0.01, 0.55 ± 0.03 vs 1.00 ± 0.01), P62 (0.94 ± 0.27, 0.66 ± 0.38 vs 1.00 ± 0.19, P < 0.05), and higher protein expression levels of FOXO3a (1.14 ± 0.03, 1.22 ± 0.05 vs 1.00 ± 0.02), PINK1 (1.46 ± 0.03, 1.56 ± 0.03 vs 1.00 ± 0.05), PARKIN (1.98 ± 0.02, 2.33 ± 0.11 vs 1.00 ± 0.06), LC3 (4.10 ± 0.58, 4.93 ± 0.33 vs 1.00 ± 0.13, P < 0.05). Conclusion:Exposure to fluoride can cause renal tissue injury in rats, with downregulation of SIRT3 and P62 expression levels, and upregulation of FOXO3a, PINK1, PARKIN, and LC3 expression levels.

Objective To explore the influencing factors of aggressive behavior in patients with bipolar disorder and to construct a nomogram prediction model.Method Eighty patients with bipolar disorder who were admitted to our hospital from March 2021 to April 2023 were selected as the research subjects.They were divided into non-aggressive and aggressive groups.Univariate analysis was performed on the data of the two groups,and factors with statistical significance were subjected to logistic regression analysis.A nomogram was drawn to determine the influencing factors of aggressive behavior in patients with bipolar disorder.Result A total of 80 patients were included,of which 28 were in the aggressive group(35.0%)and 52 were in the non-aggressive group(65.0%).The proportion of patients who lived alone for a long time,the total hospitalization time,and the proportion of patients with a history of suicidal tendencies were higher in the aggressive group than in the non-aggressive group.Moreover,the scores of ITAQ and SSRS were lower in the aggressive group(P<0.05).Multivariate logistic regres-sion analysis showed that living alone for a long time and having a history of suicidal tendencies were risk factors for aggressive behavior in patients with bipolar disorder,while high scores on ITAQ and SSRS were protective factors(P<0.05).A nomogram was constructed,which has good predictive value.Conclusion Long-term solitary living and a history of suicidal tendencies may increase the risk of aggressive behavior in patients with bipolar disorder.

Systemic lupus erythematosus(SLE)is a diffuse,systemic autoimmune disorder that can impact multiple organs and systems,with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum.It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE,as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity.Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions.In most instances,conventional treatment merely alleviates symptoms and necessitates lifelong immuno-therapy.A limited number of clinical cases have explored chimeric antigen receptor T cells(CAR-T)therapy as a potential treatment for autoimmune diseases such as SLE.Research indicates that CAR-T can specifically target CD 19 expressed on the surface of B cells and plasma cells,achieving profound de-pletion while minimizing drug-related side effects.This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team;following treatment,she ceased steroid and immunomodulator use,attaining sustained remission without these medications.The patient was a 23-year-old female.Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA(dsDNA)antibody and low complement C3.Renal biopsy in our hospital showed lupus nephritis Ⅳ-G(A/C),and National Institu-tes of Health(NIH)activity index(AI)score=4.She was diagnosed with"SLE,lupus nephritis(LN)".She was treated with hormones,immunosuppressants and Chinese medicine,but the effect was not good.After the CAR-T treatment,She stopped using hormones and immune agents and achieved con-tinuous remission with zero hormones and zero immune agents.She became pregnant six months after CAR-T infusion,and gave birth to a healthy full-term,full-weight baby successfully.She is the first pa-tient in China who successfully discontinued hormone,immune preparations and gave birth after CAR-T therapy.During the follow-up of the patient,we found that the immune indexes had basically returned to normal,and the safety was good.It indicates that CAR-T therapy may represent a promising and innova-tive therapeutic approach for the management of SLE.This offers hope and establishes a precedent for SLE women of childbearing age.

OBJECTIVE: To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM). METHODS: Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event. CONCLUSION Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM.
Female ; Male ; Humans ; Child ; Child, Preschool ; Adolescent ; Cytoskeletal Proteins ; Family ; Genetic Counseling ; Genetic Testing ; Cardiomyopathy, Hypertrophic/genetics*

Objective:To analyze the risk factors associated with retinal detachment in patients with myopia, and to establish and validate the predictive column-line diagram model.Methods:A cross-sectional clinical study. From January 2020 to November 2021, 90 patients with myopia combined with retinal detachment who were diagnosed by ophthalmologic examination in the People's Hospital of Ningxia Hui Autonomous Region were included in the study (observation group). Ninety myopic patients with age- and gender-matched myopia who underwent ophthalmologic examination for myopia during the same period were selected as the control group. The clinical data of the two groups were analyzed, and the indicators with differences were subjected to univariate and multivariate logistic regression analyses. The results of the regression analyses were visualized by using R software to obtain the column charts, and the accuracy of the column charts was verified by the ROC curves of the subjects' work characteristics; the clinical efficacy of the column chart model was verified by the internal data.Results:Compared with the control group, patients in the observation group were older, had higher myopic refraction, had more visual fatigue, ocular trauma, and cataracts, had lower choroidal and retinal thickness, and had more history of ophthalmic surgery, and the differences were statistically significant ( P<0.05). The area under the ROC curve (AUC) for age, myopic refraction, retinal thickness, and choroidal thickness were 0.612, 0.613, 0.720, and 0.704, respectively; the optimal cutoff values were 43 years old, -3.5 D, 225 μm, and 144 μm. the ROC values were 0.612, 0.613, 0.720, and 0.704 for age (>43 years old), myopic refraction (>-3.5 D), visual fatigue (yes), ocular trauma (yes), cataracts (yes), retinal thickness (≤225 μm), and choroidal thickness (≤144 μm) were the risk factors affecting the development of retinal detachment in myopic patients ( P<0.05). The consistency index of the column chart model for predicting the risk of retinal detachment in patients with myopia was 0.731 (95% confidence interval 0.665-0.824); the risk threshold for predicting the development of retinal detachment in patients was >0.07. Conclusions:Age >43 years, myopic refraction >-3.5 D, presence of visual fatigue, ocular trauma, cataract, retinal thickness ≤225 μm, choroidal thickness ≤144 μm are the risk factors affecting the development of retinal detachment in myopic patients. The column-line diagram model constructed on the basis of the risk factors has good accuracy.