Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

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Objective To investigate the effect of NK cells on the proliferation of four kinds of colorec-tal cancer(CRC)lines,and to explore the feasibility of adoptive NK cell immunotherapy in the treatment of CRC so as to provide an experimental basis for the diagnosis and treatment of CRC.Methods Peripheral blood mononuclear cells were isolated by the Ficoll density gradient centrifuge method,which were in vitro in-duced to activate as the NK cells and amplified.The CCK-8 method was used to detect the effect of NK cells on the proliferation of CRC cell lines RKO,HCT15,HCT116 and LoVo.The inhibition rate of NK cells on CRC cell lines was statistically analyzed and compared.Results The inhibitory rate of NK cells against the same target cells was significantly different at different effect target ratios(P＜0.05).Under different num-ber of target cells(5 × 103 vs.1 × 104),the inhibitory rate of NK cells against RKO(effect-target ratio 0.4∶1),HCT15(effect-target ratio 0.4∶1 and 0.2∶1),HCT116(effect-target ratio 3.2∶1,1.6∶1,0.8∶1,0.4∶1 and 0.2∶1)and LoVo(effect-target ratio 1.6∶1,0.8∶1,0.4∶1,0.2∶1 and 0.1∶1)were significantly different(P＜0.05),while no statistical differences were found among other groups(P＞0.05).The effect-target ratio corresponding to the maximum inhibitory rate of NK cells against four CRC cell lines was 12.8∶1 under different target cell numbers.Conclusion Adoptive NK cell immunotherapy has an impor-tant significance for the early intervention and treatment of CRC,moreover 12.8∶1 may be a safe and effec-tive effect-target ratio.

Objective To extract and summarize the clinical registration information of periodontitis registered in the US ClinicalTrials.gov and Chinese Clinical Trial Registry(ChiCTR),and further analyze the registration characteristics of periodontitis clinical trials.Methods The ClinicalTrials.gov and ChiCTR data-bases were searched and compiled for periodontitis clinical registration information from 2000 to December 26,2024,including registration number,country/region of registration,annual number of registered projects,sample size,study type and design,study phase,and trial progress status.Results As of December 26,2024,a total of 520 242 registered clinical trials were retrieved from the ClinicalTrials.gov registry platform,of which 1 542(0.30%)were related to periodontitis.There were 189(12.26%)studies on periodontitis-related pro-jects in Turkey,while a total of 37(2.4%)projects were initiated by researchers in China,which ranked ninth.The Chinese Clinical Trial Register(ChiCTR)had 92 954 registered projects,of which 165 were on pe-riodontitis,and most of them were conducted by well-known affiliated hospitals and stomatology hospitals.The number of registrations in the ClinicalTrials.gov database increased year by year and reached a peak in 2022(146 registrations).Trial designs were focused on interventional and observational studies.ClinicalTri-als.gov study phases were focused on phases 2 and 4,while ChiCTR was clustered at phase 0(pre-registra-tion).Conclusion The number of clinical registrations for periodontitis in China's database is relatively low,and despite a steady upward trend,there is still a gap compared with other countries internationally.Future re-search should focus on how to encourage more oral health related research institutions to register on the plat-form and how to increase the sample size.

BACKGROUND:As a member of bone morphogenetic proteins,growth differentiation factor-5 shows promising potential in the application of cartilage and bone repair.The affinity of growth differentiation factor-5 onto bone tissue determines protein use efficiency,so it is of great significance to prepare growth differentiation factor-5 with bone targeting capability. OBJECTIVE:To modify growth differentiation factor-5 using bisphosphonates and investigate the effects of modified protein on the growth of preosteoblasts in mice. METHODS:Pamidronate disodium/growth differentiation factor-5 complex was prepared using chemical crosslinking to couple growth differentiation factor-5 with pamidronate disodium.The functional groups and structures of the complex were characterized using Fourier transform infrared spectroscopy and circular dichromatography.To determine the bone targeting in vitro,the binding of the modified growth differentiation factor-5 with calcium phosphate and in vitro release amount of growth differentiation factor-5 were measured with an ELISA kit.Growth differentiation factor-5(control group)and the pamidronate disodium/growth differentiation factor-5 complex(experimental group)were co-cultured with preosteoblasts MC3T3-E1.Individually cultured cells were blank controls.The effect of the complex on cell proliferation and differentiation was evaluated. RESULTS AND CONCLUSION:(1)The infrared spectroscopy and circular dichromatography results indicated that the bisphosphonate/growth differentiation factor-5 complex was successfully prepared without significant changes in the protein secondary structure.In vitro protein adsorption results showed that growth differentiation factor-5 adsorption on calcium phosphate was increased by about one time after coupling with a bisphosphonate.In the presence of cysteine,growth differentiation factor-5 could be released from the bisphosphonate/growth differentiation factor-5 complex.(2)CCK-8 assay results showed that the absorbance value of the experimental group cultured for 4 and 7 days was higher than that of the control group and blank control group(P<0.000 1).After 7 days of culture,the expression of alkaline phosphatase in the experimental group was significantly higher than that in the control group and blank control group(P<0.000 1).After 13 days of culture,the content of calcium nodules in the experimental group was significantly higher than that in the control group and the blank control group(P<0.000 1).The results of qRT-PCR showed that the mRNA expression of alkaline phosphatase,osteocalcin and Runx2 in the experimental group was higher than that in the control group and the blank control group after 7 days of culture(P<0.01,P<0.001,P<0.000 1).(3)These findings exhibit that bisphosphonate modification can enhance the binding capacity of growth differentiation factor-5 to calcium phosphate as well as improve its biological activity.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Neoplasm Staging ; Survival Rate ; Retrospective Studies

Objective:To investigate the effect of resveratrol on the expression of inflammatory cytokines and related genes in human SZ95 sebocytes induced by benzo (a) pyrene.Methods:Human SZ95 sebocytes were cultured in vitro, and divided into 4 groups: control group treated with 1‰ dimethyl sulfoxide for 27 hours, resveratrol group treated with 1 × 10 -5 mol/L resveratrol for 24 hours, benzo (a) pyrene group treated with 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours, resveratrol+benzo (a) pyrene group treated with 1 × 10 -5 mol/L resveratrol for 24 hours followed by 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of interleukin (IL) -1α, IL-6, aryl hydrocarbon receptor (AhR) , cytochrome P4501A1 (CYP1A1) and cytochrome P4501B1 (CYP1B1) in SZ95 sebocytes in the above groups; Western blot analysis was conducted to determine the phosphorylation level of p38 mitogen-activated protein kinase (p38 MAPK, expressed as the ratio of phosphorylated to total p38 MAPK) and AhR protein expression; enzyme-linked immunosorbent assay (ELISA) was conducted to detect levels of IL-1α and IL-6 in the cell culture supernatant in each group. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:The mRNA and protein expression of IL-1α in SZ95 sebocytes significantly differed among the control group, resveratrol group, benzo (a) pyrene group and resveratrol+benzo (a) pyrene group (mRNA: 2.045 ± 0.272, 2.058 ± 0.154, 3.124 ± 0.094, 2.185 ± 0.337, protein: 9.132 ± 1.181, 9.429 ± 0.771, 20.361 ± 0.907, 9.917 ± 0.897, F=14.662, 101.705, P < 0.01, < 0.001, respectively) , and were significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group (both P < 0.01) . In addition, the phosphorylation level of p38 was significantly higher in the benzo (a) pyrene group than in the control group, resveratrol group and resveratrol+benzo (a) pyrene group ( F=303.129, P < 0.000 1) . The mRNA expression of AhR, CYP1A1 and CYP1B1 was significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group ( t=10.64, 33.599, 18.327, respectively, all P < 0.001) . The benzo (a) pyrene group showed significantly decreased protein expression of AhR compared with the resveratrol+benzo (a) pyrene group ( P < 0.001) . Conclusion:Resveratrol can inhibit the environmental pollutant benzo (a) pyrene-induced expression of inflammatory factor IL-1α in SZ95 sebocytes, which is likely mediated by the AhR and p38MAPK pathways.

Astrocytes are the most abundant cells in the central nervous system and play significant roles in normal brain. With cerebral infarction, astrocytes are activated as reactive astrocytes and form glial scars, which play an essential part in brain injury. According to their roles in neuroprotection after cerebral infarction, regulation of scar formation, nerve regeneration, maintenance of blood-brain barrier, promotion of angiogenesis and immune response, scholars have proposed a variety of therapeutic strategies based on targeting astrocytes. This article reviews the research progress on the changes in astrocyte signaling pathways before and after cerebral infarction and the related therapeutic strategies.
Astrocytes ; Cerebral Infarction ; physiopathology ; therapy ; Humans ; Neuroglia ; pathology ; Signal Transduction