Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective:To study the epidemic characteristics and spatio-temporal distribution of scrub typhus in Hangzhou City.Methods:The case information of scrub typhus in Hangzhou City from 2010 to 2022 was collected through the Infectious Disease Surveillance and Reporting Information System of China Disease Prevention and Control Information System, and the incidence, time, population, and regional distribution characteristics of scrub typhus were analyzed. With street (township) as the unit, ArcGIS 10.2 software was used for global and local spatial autocorrelation analysis, SaTScan 10.1.2 software was used for spatio-temporal aggregation scanning.Results:From 2010 to 2022, a total of 362 cases were reported in Hangzhou City, with a median annual incidence of 0.260/100 000. The incidence showed a fluctuating upward trend year by year ( Z = 3.84, P < 0.001). The highest incidence was 0.528/100 000 in 2021 and the lowest incidence was 0.013/100 000 in 2010. The median time interval between onset and diagnosis was 7 days, ranging from 1 to 28 days. The peak incidence period was from September to November (52.49%, 190/362). There were 149 males (41.16%, 149/362) and 213 females (58.84%, 213/362). The age group of 60 - 69 years old had the highest number of cases, accounting for 32.32% (117/362). The majority of occupations were farmers (77.35%, 280/362). The top 3 regions with reported cases were Chun'an County (257 cases, 70.99%), Lin'an District (33 cases, 9.12%), and Jiande City (19 cases, 5.25%). Global spatial autocorrelation analysis showed that there was spatial aggregation in the incidence of scrub typhus in other years except 2015 - 2018 ( P < 0.05). Local spatial autocorrelation analysis showed that, except for 2015 and 2016, the incidence of scrub typhus in other years occurred in hot spots (high-high), which were all located in Chun'an County. The spatio-temporal aggregation analysis showed that the class Ⅰ cluster was centered around Jinfeng Township in Chun'an County, with a clustering period from December 2018 to November 2021, involving 22 townships. The class Ⅱ cluster was centered around Wanshi Township in Fuyang District, with a clustering period from December 2021 to November 2022, involving 14 streets (townships). Both of the two clusters were mountainous agricultural areas, with reported cases accounting for 38.67% (140/362). Conclusions:In Hangzhou City, the majority of scrub typhus cases are elderly female farmers, with a high incidence season in autumn, mainly occurring in agricultural areas in mountainous areas. It is recommended to carry out comprehensive prevention and control measures such as health education and personal protection for key populations, seasons and regions.

Objective:To study the epidemiological and spatio-temporal distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Hangzhou City, providing a scientific basis for prevention and control of HFRS.Methods:Data of HFRS cases reported in Hangzhou City from January 1, 2010 to December 31, 2022 were collected through the Infectious Disease Surveillance and Reporting Information System of China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the prevalence and three-distribution characteristics of HFRS in Hangzhou City. Joinpoint regression was used to analyze the trend of HFRS incidence in Hangzhou City from 2010 to 2022. Global and local spatial autocorrelation were used to analyze the spatial distribution pattern of HFRS and the hotspots of incidence in Hangzhou City. And spatio-temporal scanning was used to analyze the spatio-temporal aggregation areas of HFRS in Hangzhou City.Results:From 2010 to 2022, a total of 224 HFRS cases were reported in Hangzhou City, with an average annual incidence of 0.18/100 000. The distribution of cases showed obvious seasonality, with peak incidence in spring (March to May) and autumn (September to November), accounting for 30.80% (69/224) and 26.34% (59/224), respectively. HFRS cases were reported in all districts (counties, cities) of the city, among which Xiaoshan District (66 cases, 29.46%), Chun'an County (41 cases, 18.30%) and Jiande City (25 cases, 11.16%) ranked the top three. The majority of the cases were individuals aged 31 to 60 (65.18%, 146/224), males (74.55%, 167/224), and farmers (46.43%, 104/224). Joinpoint regression analysis indicated that the overall incidence of HFRS in Hangzhou City was in downward trend from 2010 to 2022 [average annual percent change (AAPC) = - 5.01%, 95% confidence intervals ( CI): - 9.46% to - 0.34%, t = - 2.10, P = 0.036]. Global spatial autocorrelation analysis showed that there was a positive spatial correlation in the incidence of HFRS among various streets (townships) in Hangzhou City from 2011 to 2014, 2018, and 2020 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis showed that from 2010 to 2022, the number of streets (towns) in hot areas (high-high) in Hangzhou City was 0, 2, 3, 3, 3, 3, 0, 0, 4, 0, 1, 0, and 1, respectively, and was relatively fixed in the southwest districts (counties, cities). Spatio-temporal scan analysis identified three clusters: Cluster I was from August 2011 to January 2015, centered on Fenkou Town in Chun'an County, involving 5 townships in Chun'an County; Cluster Ⅱ-1 was from August 2012 to March 2016, centered on Puyang Town in Xiaoshan District, involving 5 townships in Xiaoshan District; Cluster Ⅱ-2 was from June 2019 to June 2020, centered on Xiaya Town in Jiande City, not involving other streets (townships). Conclusions:From 2010 to 2022, the majority of HFRS cases in Hangzhou City are middle-aged male farmers. The overall trend of HFRS epidemic is decreasing, mainly concentrated in the southwest districts (counties, cities) of Hangzhou City. In the future, precise prevention and control measures should be implemented in key areas and among key populations.

Objective:To investigate the effect of puerarin on myocardial inflammation in rats with heart failure from the Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)inflammatory pathway.Methods:The rat model of heart failure was established by subcutaneous injection of isoproterenol(5 mg/kg for 7 days),and was divided into model group,puerarin group,TLR4 activator group(RS09,25 μg/kg),TLR4 inhibitor group(TAK-242,0.5 mg/kg),puerarin+TLR4 activator group,with 20 rats in each group.Another 20 rats were selected as normal control group.Echocardiography was used to detect heart function;HE staining was used to observe pathological damage of myocardial tissue;TUNEL method was used to detect apoptosis of myocardial tissue cells;ELISA method was used to detect the levels of inflammatory factors IL-6,IL-1β and tumor necrosis factor-α(TNF-α)in myocardial tissue;immunohistochemical method was used to detect the expression of TLR4 and macrophage activation marker-F4/80;Western blot was used to detect the protein expressions of TLR4/NF-κB pathway,MyD88,IL-1 receptor-associated kinase(IRAK)and Galec-tin-3.Results:Compared with the normal control group,the necrosis,inflammatory infiltration and apoptosis of rat myocardial cells were severe in the model group,the heart function was decreased,the inflammatory factor release,macrophage activation,and TLR4/NF-κB pathway protein expression were increased(P<0.05).Puerarin and TLR4 inhibitors could improve the pathological damage of heart failure rats such as myocardial cell necrosis,inflammatory infiltration and apoptosis to the same extent,improve heart function,reduce inflammatory response,inhibit macrophage activation and reduce TLR4/NF-κB pathway activation(P<0.05).TLR4 activator could promote the activation of TLR4/NF-κB pathway,aggravate myocardial cell damage,apoptosis and cardiac function damage in rats with heart failure,and weaken the above-mentioned effects of puerarin(P<0.05).Conclusion:Puerarin may inhibit the activation of TLR4/NF-κB pathway,reduce myocardial inflammation,and play an anti-heart failure effect.

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.
Dentistry ; Artificial Intelligence

Objective:To observe the clinical efficacy of ultrasound cycloplasty (UCP) in the treatment of uncontrolled intraocular pressure (IOP) after glaucoma surgery.Methods:An observational case series study was carried out.Twenty-eight consecutive patients (28 eyes) with uncontrolled IOP after glaucoma surgery who received UCP treatment in The First Affiliated Hospital of Zhengzhou University from July 2018 to October 2019 were enrolled.The IOP of these patients was ≥21 mmHg (1 mmHg=0.133 kPa) under the maximum tolerated dose.According to preoperative IOP and visual acuity, the patients were divided into 8-sector group (17 eyes) and 10-sector group (11 eyes). The duration of UCP operation, preoperative and postoperative 1-day, 1-week, 2-week, 1-month and 3-month IOP and BCVA, the types of drugs for lowering IOP preoperatively and postoperatively, preoperative and postoperative 3-month ocular pain grading and corneal endothelial cell counts, and adverse reactions during the operation and after surgery were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-154). Written informed consent was obtained from each subject prior to any medical examination.Results:The duration of UCP operation was 3 to 7 minutes, with an average of (4.30±1.26) minutes.The IOP at 1 day, 1 week, 2 weeks, 1 month and 3 months after operation was (32.96±10.49), (25.89±7.25), (24.50±6.23), (24.07±6.59), (24.32±6.52)mmHg, respectively, which were significantly lower than (45.82±8.81) mmHg before operation (all at P<0.05). There was no significant difference in IOP between the 8-sector group and 10-sector group ( Fgroup=1.271, P=0.270), but there was a significant difference in IOP between the two groups before and after operation ( Ftime=54.388, P<0.01), and the postoperative IOP at various time points in the two groups were lower than the preoperative IOP, showing statistical significances (all at P<0.05). There was no significant difference in BCVA before and after surgery ( F=2.562, P=0.075). There was a statistically significant difference in BCVA between the 8-sector group and 10-sector group ( Fgroup=12.602, P=0.001), but no statistically significant difference was found in BCVA between the two groups before and after surgery ( Ftime=1.701, P=0.139), and the BCVA in the 8-sector group was better than the 10-sector group at various time points (all at P<0.05). The types of IOP lowering drugs used in the 8-sector group and 10-sector group were 3 (2, 3) and 3 (2, 4) before operation respectively, and 0 (0, 1) and 0 (0, 0) at 3 months after operation respectively.The preoperative ocular pain grade was 2 (2, 2), and the postoperative 3-month ocular pain grade was reduced to 1 (0, 1), and the difference was statistically significant ( Z=-4.824, P<0.05). The postoperative 3-month pain grading in the 8-sector and 10-sector groups were significantly lower than the preoperative pain grading ( Z=-3.739, -3.127; both at P<0.05). The corneal endothelial cell count was significantly decreased from (1 967.15±186.06) cells/mm 2 before operation to (1 861.08±206.63) cells/mm 2 at 3 months after operation ( t=2.781, P=0.017). No serious complications occured during the operation.Postoperative adverse reactions included chemosis and bulbar hyperemia, corneal edema, headache, ocular pain, anterior chamber inflammation, etc.Serious complications such as low IOP, macular edema, vision loss or eyeball atrophy were not observed. Conclusions:UCP has no surgical incision.Treatment of both 8 sectors and 10 sectors can effectively reduce IOP, reduce the types of IOP lowering drugs, and relieve ocular pain in patients with uncontrolled IOP after glaucoma surgery with few intraoperative and postoperative adverse reactions.

OBJECTIVE：To desig n and sy nthesize poly （γ-glutamic acid ）-ampelopsin（γ-PGA-AMP），and to characterize it and evaluate its anti-tumor activity in vitro . METHODS ：Synthetic product was produced through an esterification reaction between γ-PGA and ampelopsin. The structure of synthetic product was characterized by the UV spectrophotometry ，Fourier transform infrared（FT-IR）spectroscopy，1H-NMR spectra and the quantitative elemental analysis. The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm. Using 5-FU as positive control ，MTT assay was used to determine inhibitory effects of γ-PGA-AMP and ampelopsin on human breast cancer cell MCF- 7，human liver cancer cell HepG 2 and human lung cancer cell A 549. The IC 50 was calculated. RESULTS ：The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group of γ-polyglutamic acid had been esterified to obtain γ-PGA-AMP；the yield of γ-PGA-AMP was 55.7％，and the content of ampelopsin was 32.3％. The inhibitory effect of γ-PGA-AMP and ampelopsin on MCF- 7，HepG2 and A 549 cells was obvious. IC 50 of γ-PGA-AMP（to 3 above tumor cells ）were 40.19，28.29 and 55.23 μg/mL，those of ampelopsin were 105.30，81.23，130.10 μg/mL，those of 5-FU were 24.72，87.98，30.99 μg/mL，respectively. CONCLUSIONS ：γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully ，and its anti-tumor effect is stronger than that of ampelopsin.

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m 2; while when BMI was greater than 31.2 kg/m 2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.

OBJECTIVE： To study the effects of ethanol extract of Sanguis Draconis on the survival of perforating flap model in rats and PI3K/Akt/eNOS pathway. METHODS： Perforating flap model was established by cutting off surrounding vessels and keeping one perforator. After modeling， the rats were divided into model group （external use， normal saline） and ethanol extract of Sanguis Draconis （EESD， the content of dracorhodin was 75.08 mg/g） group （external use， 0.21 g/cm2）， with 10 rats in each group. They were given relevant medicine for consecutive 7 days， once a day. The flap survival rate and flap microvessel density were determined after given relevant medicine 7 days. Human umbilical vein endothelial cells （HUVECs） were reoxygenated and glycoconjugated 16 h after hypoxia and hypoglycemia to establish oxygen-glucose deprivation/oxygen-glucose recovery model of HUVECs. After modeling， model cells were divided into normal group， model group， dracorhodin high-concentration， medium- concentration and high-concentration groups （2.5， 1.0， 0.5 μg/mL）. After reoxygenated and glycoconjugated for 24 h， cells morphology was observed by microscope； cell viability and the content of NO were detected by MTT assay and colorimetry. mRNA expression of Akt， PI3K and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were determined by RT-PCR and Western blot assay. RESULTS： In rat experiment， compared with model group， flap survival rate and microvessel density of rats were increased significantly in EESD group （P＜0.01）. In cell experiment， compared with normal group， the survival rate of HUVEC， NO content， mRNA expression of PI3K， Akt， eNOS，PI3K protein expression， the phosphorylation of Akt and eNOS protein were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， dracorhodin high-concentration， medium-concentration and high-concentration groups survival rate of HUVEC cells， NO content， mRNA expression of PI3K， Akt and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The survival rate of perforating flap model in rat can be increased by treating with EESD， the mechanism of which may be associated with the activation of PI3K/Akt/eNOS pathway to protect endothelial cells.