BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

Objective To explore the clinical characteristics of pediatric patients with cerebral palsy(CP)who also have comorbid epilepsy.Methods A retrospective analysis was conducted on the clinical data of 155 pediatric patients with CP and comorbid epilepsy admitted to the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022.Patients were divided into 4 groups based on CP subtype:spastic diplegia group(n=29),spastic hemiplegia group(n=33),spastic quadriplegia group(n=73),and non-spastic group(n=20).Differences in sex,season of birth,birth weight,gestational age,and the relationship between gestational age and weight were compared among the groups.Additionally,the relationships between perinatal risk factors,MRI classification system(MRICS),gross motor function classification system(GMFCS),and the age of the first onset of epilepsy with respect to CP subtype were analyzed.Results Among the 155 patients,101 were male and 54 were female.A lower proportion of patients with spastic hemiplegia was observed with a gestational age of 28-31+6 weeks compared with those with spastic diplegia and spastic quadriplegia(P=0.009).The proportion of patients with a history of asphyxia in spastic hemiplegia group was significantly lower than that in the other 3 groups,and the proportion of patients with hypoxic-ischemic encephalopathy(HIE)in spastic hemiplegia group was significantly lower than in that both spastic quadriplegia group and non-spastic group(P<0.05).The proportion of patients in spastic quadriplegia group who had their first seizure at an age of<1 year was significantly higher than that in spastic diplegic group(P=0.041).The spastic diplegia group exhibited a higher percentage of white matter damage compared with the other 3 groups,and had a lower percentage of gray matter damage compared with both spastic hemiplegic group and non-spastic group(P=0.001).The proportion of patients with GMFCS levels Ⅳ-Ⅴ in spastic quadriplegia group was higher than those in the other 3 groups(P<0.001),and the proportion of patients with levels Ⅰ-Ⅲ in spastic hemiplegia group was significantly higher than those in spastic quadriplegia group and non-spastic group(P<0.001).Conclusion Significant differences were observed among pediatric patients with different subtypes of CP and comorbid epilepsy in factors such as gestational age,history of asphyxia,HIE history,age of first seizure,MRICS classification and GMFCS levels.

Objective To analyze the risk factors of lower limb deep vein thrombosis(DVT)after the closed Pilon fracture surgery,and to build a nomograph prediction model.Methods A total of 182 patients with closed Pilon fracture who underwent surgical treatment in our hospital from June 2019 to June 2022 were retrospectively analyzed,according to the occurrence of postoperative DVT,the patients were divided into two groups:43 cases in DVT group and 139 cases in non-DVT group.Univariate and multivariate Logistic regression analysis was applied to screen the risk factors of lower limb DVT after closed Pilon fracture surgery;R software was applied to build a nomograph model for predicting lower limb DVT after closed Pilon fracture surgery,and receiver operating characteristic(ROC)and calibration curve were applied to verify the nomograph model.Results Logistic regression analysis showed that the history of diabetes mellitus,risk assessment of thrombosis as medium and high risk,and postoperative infection were independent risk factors for lower limb DVT after closed Pilon fracture surgery(P＜0.05).The area under the ROC curve was 0.716(95％CI:0.629-0.804).The slope of calibration curve was close to 1,and H-L goodness of fit test x2=2.556,P=0.635.Conclusion The history of diabetes,the result of thrombosis risk assessment as"medium-high risk",and the postoperative infection occurred at the surgical site are independent risk factors for lower limb DVT after closed Pilon fracture surgery.The nomogram prediction model constructed by integrating the above three independent risk factors can effectively predict lower limb DVT after closed Pilon fracture surgery,with high differentiation and consistency.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.