ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

[Purpose]To analyze the trends of cervical cancer incidence in Qidong City of Jiangsu Province from 1977 to 2021.[Methods]Based on the cervical cancer registration database in Qi-dong City from 1977 to 2021,the crude incidence rate,the age-standardized rate by the standard Chinese standard population and the world standard population(ASRC and ASRW),the truncated rate of 35～64 years old,the cumulative rate of 0～74 years old,and the cumulative risk were cal-culated;the incidence rates of birth cohorts were analyzed.Joinpoint regression analysis was per-formed with Joinpoint 4.9.0.0 software to calculate the annual percentage change(APC)and the average annual percentage change(AAPC)of cervical cancer incidence.[Results]A total of 2 253 new cases of cervical cancer registered in Qidong City from 1977 to 2021,accounting for 1.62％of the total case numbers of cancer in the whole population,and for 4.03％of the total number of cancers in women.The crude incidence rate was 8.75/105,the ASRC was 4.54/105,the ASRW was 6.01/105,the truncated rate(35～64 years old)was 15.09/105,the cumulative rate(0～74 years old)was 0.63％,and the cumulative risk was 0.63％.The incidence of cervical cancer increased with age from 1977 to 2021.The average incident age was 55.36 years old,with the lowest age of 47.51 years old in 2010.Secular trend analysis showed that the AAPC of the crude incidence of cervical cancer was 6.010％(95％CI:4.951％～7.081％)(P＜0.001),among which the trend decreased from 1977 to 1999,with an APC of-2.507％;and then the trend increased from 1999 to 2017,with an APC of 14.436％(P＜0.001).The rising and falling trend curves of the AS-RC and ASRW were similar to that of the crude incidence.The age group and time period analysis showed that the peak incidence was in the older age groups before 2006,while the peak inci-dence appeared in the age groups of 45～54 years old from 2007 to 2021.The AAPCs in age groups of 25～64 years old demonstrated upward trends(all P＜0.05).The birth cohort analysis showed that the cervical cancer incidence in the 1937-1941 birth cohort was the lowest,and the birth cohort-specific rates in all age groups showed"V-shape"trends.[Conclusion]Long-term monitoring of cervical cancer incidence in Qidong has shown a trend of initially slow decline fol-lowed by a rapid increase,with the peak incident shifting towards younger ages.The rising trends of cervical cancer incidence in last two decades may be associated with the increased HPV infection,suggesting that measures to reduce HPV infection and enhance vaccination should be strengthened.

[Purpose]To analyze global epidemic status of colorectal cancer and explore the rela-tionship between the human development index(HDI)and the burden of colorectal cancer.[Methods]Based on the GLOBOCAN 2022 estimation data,the disease burden of colorectal can-cer in different regions,countries,and levels of HDI were analyzed.Spearman's rank test was used to explore the correlation between HDI and colorectal cancer disease burden.[Results]The estimated global incidence of colorectal cancer in 2022 was 1 926 425 cases(1 069 446 for male and 856 979 for female),with a age-standardized incidence rate of 18.4/105(21.9/105 for male and 15.2/105 for female),and cumulative risk of incidence of 2.10％(2.60％for male and 1.70％for female);the estimated number of deaths was 904 019(499 775 for male and 404 244 for fe-male),with a age-standardized mortality rate of 8.1/105(9.9/105 for male and 6.5/105 for female)and cumulative risk of death of 0.84％(1.00％for male and 0.65％for female).1-crude mortality rate/crude incidence rate(1-M/I)was 0.53(0.53 for male and 0.53 for female).Large disparities were in the disease burden of colorectal cancer between different regions and countries.After grouped by HDI,we found that the age-standardized incidence rates in very high,high,median,and low HDI regions were 28.6/105,18.1/105,6.7/105,and 6.4/105,and the standardized mortality rates were 10.5/105,8.3/105,3.9/105,and 4.5/105,with 1-M/I of 0.57,0.52,0.43 and 0.30,respec-tively;and the incidence and mortality rates were increasing with age.Spearman's correlation analysis showed a strong positive correlation between HDI and colorectal cancer in age-standardized incidence(r=0.84),age-standardized mortality(r=0.71)and 1-M/I(r=0.82)(all P＜0.001).[Con-clusion]The global burden of colorectal cancer remains high.There are disparities in the disease burden among countries and regions,which is positively correlated with their HDI levels,indicating that the colorectal cancer prevention and treatment strategies should be developed based on the conditions of each regions and countries accordingly.

[Purpose]To analyze the incidence trend and age,period,cohort effects of brain and other central nervous system tumors(brain tumor)in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of brain tumor from 1972 to 2021 were collected from the Qidong cancer registry database.The crude incidence rate(CR),age-standardized rate by Chi-nese standard population(ASRC),age-standardized rate by world standard population(ASRW)and average annual percentage change(AAPC)were calculated.The age-period-cohort(APC)model was used to analyze the age,period,and cohort effects of brain tumor incidence in Qidong City from 1972 to 2021.[Results]A total of 2 801 cases of brain tumor occurred in Qidong City from 1972 to 2021,including 1 475 male cases and 1 326 female cases.From 1972-1976 to 2017-2021,the CR increased from 1.81/10 5 to 9.28/10 5,the ASRC increased from 2.07/10 5 to 4.96/10 5,and ASRW increased from 2.00/105 to 4.98/105.From 1972 to 2021 the AAPC of CR,ASRC and ASRW were 3.97％(3.53％for male and 4.37％for female),2.02％(1.66％for male and 2.24％for female)and 2.06％(1.63％for male and 2.24％for female)(all P＜0.001).The Wald's Chi-square test of the APC model showed that there were significant differences in the trends of age,period and birth cohort effect of brain tumor risk(all P＜0.05).The age effect showed that the incidence of brain tumor increased with age,starting from the age group of 45～49 years old and reaching a peak of 25.84/10 5 in age group of 75～79 years old(95％CI:21.17/10 5～31.53/10 5).The period ef-fect showed that the risk of recent period was higher than that in the early period using 1992-1996 period as the reference,reaching the highest in 2012-2016(RR=1.64,95％CI:1.38～1.95).The birth cohort effect showed that the highest risk was in 2017-2021 births cohort(RR=11.17,95％CI:4.26～29.26)using 1952-1956 birth cohort as the reference.[Conclusion]The incidence of brain tumor in Qidong City has been rising;and age,period and cohort are the main influencing factors,suggesting that the middle-aged and elderly population should be the focus of brain tumor prevention and control.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To describe and analyze the incidence, mortality and epidemiological trends of liver cancer in China and selected regions worldwide, providing data references for liver cancer prevention and control.Methods:Data on the incidence, mortality, historical trends, and projected estimates for 2050 of liver cancer were extracted from the GLOBOCAN 2022 database. Epidemiological characteristics of liver cancer in China and other region were described and compared by region, age, sex and human development index (HDI). Spearman's test was used to examine the relationships between HDI and age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) across regions. The average annual percentage change (AAPC) in ASIR was calculated using Joinpoint regression analysis.Results:In 2022, the number of new cases and deaths of liver cancer in the global were 866 000 and 759 000 respectively, and the ASIR and ASMR were 8.6/10 5 and 7.4/10 5, respectively. Both ASIR and ASMR were higher in males than in females. In China, there were 368 000 new cases and 317 000 deaths in 2022, with an ASIR of 15.0/10 5 and an ASMR of 12.6/10 5. Globally, the incidence of liver cancer in males peaked in the 65-69 age group, while in Chinese males, two incidence peaks were observed in the 50-54 and 65-69 age groups. Among the elderly (≥65 years), the global ASIR and ASMR were 7.4 and 8.1 times higher, respectively, than those in the working-age population (15-64 years). In China, the ratios of ASIR and ASMR between the elderly and working-age populations were 5.9 and 7.0, respectively. Both ASIR and ASMR were negatively correlated with HDI (ASIR: r=-0.18, P=0.018; ASMR: r=-0.31, P＜0.001). From 2002 to 2017, ASIR of liver cancer showed a declining trend in both males and females in China, Japan, and South Korea (all P＜0.001), with AAPCs of -1.96% for Chinese males and -2.75% for Chinese females. In contrast, the United States experienced an increasing trend in ASIR, with AAPCs of 3.13% for males and 3.12% for females (both P＜0.001). Projections indicate that by 2050, the number of new cases and deaths globally will reach 1.564 million and 1.421 million, representing increases of 80.6% and 87.2% compared to 2022, respectively. In China, the number of new cases and deaths are projected to be 560 000 and 514 000, increases of 52.2% and 62.1% from 2022, respectively. Conclusions:The burden of liver cancer varies significantly across regions, sexes, and age groups worldwide. Incidence and mortality rates are negatively correlated with HDI. The global burden of liver cancer is expected to continue increasing, underscoring the need for enhanced comprehensive prevention and control strategies.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective To investigate the situation of hepatitis B immune blocking and the growth and development of hepatitis B exposed children within one year after birth, and to provide evidence for formulating and optimizing measures for maternal and infant blocking in Wenzhou. Methods The hepatitis B infection status during pregnancy and birth was collected, hepatitis B immunoglobulin and vaccine were analyzed, and a follow-up on the immune blocking effect, growth and development, and the nutritional status of children exposed to hepatitis B was conducted. Statistical analysis of data was carried out through SPSS 26.0. Results In 2021, 6.07% of newborns in Wenzhou were exposed to hepatitis B, of which 28.37% were highly exposed children. The prevalence rates for males and females were 6.42% and 5.70%, respectively, and the difference was statistically significant (χ²=13.744, P<0.001). The prevalence rates in mountainous and non-mountainous counties were 6.35% and 5.94%, respectively, and the difference was statistically significant (χ²=5.72, P < 0.001). In 2021, the mother-to-child transmission rate of children exposed to hepatitis B was 0.54‰. There were no significant differences in the height, weight, hemoglobin and neuropsychological development of hepatitis B exposed children compared with non-exposed children (P < 0.001). Conclusion The number of children exposed to hepatitis B in mountainous counties is significantly higher than that in non-mountainous counties in Wenzhou, and the number of men is significantly higher than that of women. The proportion of highly exposed children is relatively high. The effect of mother-to-child blocking is good, and there is no significant difference between the growth and development of children exposed to hepatitis B and no-exposed children during follow-up.