Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

BACKGROUND:Copper is an essential trace element and plays a key role in series of physiological activities in the body.Metabolic disturbance of copper is closely associated with multiple diseases.Copper metabolism is mainly involved in the absorption,transport,storage and excretion of copper ions,and all the above processes regulate copper homeostasis in the body.In recent years,many studies have confirmed that copper homeostasis disorder severely affects the metabolic activities of the body and cause diseases in various systems.Besides,the role of copper in oral diseases has been of great interest.OBJECTIVE:To explore the role of copper in occurrence,development,and treatment of oral diseases,and provide a comprehensive overview of research advances in this field.METHODS:The first author searched relevant studies on copper in oral diseases using a computer in PubMed,Web of Science,and CNKI.The key words were"Cu,copper,copper metabolism,oral diseases,oral squamous cell carcinoma,periodontitis,oral submucous fibrosis,oral lichen planus,recurrent oral ulceration,pultitis"in English and Chinese.After screening,78 articles were included for further review and analysis.RESULTS AND CONCLUSION:(1)Patients with oral squamous cell carcinoma have elevated concentrations of copper in serum and saliva,and elevated copper promotes cancer progression through oxidative stress and promoting angiogenesis.Excessive elevation or reduction of copper concentration in tumor cells can inhibit the growth of tumor cells.The combination of copper and anticancer drugs can significantly improve the efficacy of drugs.(2)The concentration of copper in the serum of patients with periodontitis is increased,and excessive copper can aggravate periodontitis through promoting oxidative stress.Combination of copper and drugs can promote periodontal bone regeneration and periodontal tissue healing.(3)The level of copper is positively correlated with degree of oral mucosa fibrosis.Copper that enters the oral mucosa promotes fibrosis of oral mucosa by enhancing activity of lysyloxidase to increase production of collagen.(4)Copper levels are elevated in patients with oral lichen planus,and elevated copper may promote the progression of oral lichen planus by modulating immune cell function.(5)In patients with recurrent oral ulcers,serum copper level is significantly increased,and utilization of copper becomes disordered,which could decrease copper-containing enzyme activity,thus affecting the healing of ulcers.Copper is closely associated with multiple oral diseases and therapies targeting at copper could obviously enhance the therapeutic effect of drugs.But further studies are still needed to uncover its mechanisms to lay foundation for the better treatment of oral diseases.

Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

BACKGROUND:Copper is an essential trace element and plays a key role in series of physiological activities in the body.Metabolic disturbance of copper is closely associated with multiple diseases.Copper metabolism is mainly involved in the absorption,transport,storage and excretion of copper ions,and all the above processes regulate copper homeostasis in the body.In recent years,many studies have confirmed that copper homeostasis disorder severely affects the metabolic activities of the body and cause diseases in various systems.Besides,the role of copper in oral diseases has been of great interest.OBJECTIVE:To explore the role of copper in occurrence,development,and treatment of oral diseases,and provide a comprehensive overview of research advances in this field.METHODS:The first author searched relevant studies on copper in oral diseases using a computer in PubMed,Web of Science,and CNKI.The key words were"Cu,copper,copper metabolism,oral diseases,oral squamous cell carcinoma,periodontitis,oral submucous fibrosis,oral lichen planus,recurrent oral ulceration,pultitis"in English and Chinese.After screening,78 articles were included for further review and analysis.RESULTS AND CONCLUSION:(1)Patients with oral squamous cell carcinoma have elevated concentrations of copper in serum and saliva,and elevated copper promotes cancer progression through oxidative stress and promoting angiogenesis.Excessive elevation or reduction of copper concentration in tumor cells can inhibit the growth of tumor cells.The combination of copper and anticancer drugs can significantly improve the efficacy of drugs.(2)The concentration of copper in the serum of patients with periodontitis is increased,and excessive copper can aggravate periodontitis through promoting oxidative stress.Combination of copper and drugs can promote periodontal bone regeneration and periodontal tissue healing.(3)The level of copper is positively correlated with degree of oral mucosa fibrosis.Copper that enters the oral mucosa promotes fibrosis of oral mucosa by enhancing activity of lysyloxidase to increase production of collagen.(4)Copper levels are elevated in patients with oral lichen planus,and elevated copper may promote the progression of oral lichen planus by modulating immune cell function.(5)In patients with recurrent oral ulcers,serum copper level is significantly increased,and utilization of copper becomes disordered,which could decrease copper-containing enzyme activity,thus affecting the healing of ulcers.Copper is closely associated with multiple oral diseases and therapies targeting at copper could obviously enhance the therapeutic effect of drugs.But further studies are still needed to uncover its mechanisms to lay foundation for the better treatment of oral diseases.

Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Objective:To analyze the impact of the universal coverage,integration and DRG/DIP payment method reform of Basic Medical Insurance(BMI)on the equity of the health service utilization and resource allocation.Methods:The 1998-2022 panel data on health service utilization and resources were collected for China.Health equity is measured using the Concentration Index(CI)and Theil index,and the impact of BMI reform on health equity is analyzed by BP neural network and ITSA.Results:Universal coverage,integration,and DRG/DIP payment reform of BMI had a positive effect on the number of health workers,beds,and admissions(P＜0.001),and inhibited the growth of per capita hospitalization costs(P＜0.05).The CI for the number of health workers and beds declined by 0.004 and 0.003 per year after universal coverage of BMI;and both still declined by 0.002 per year with a 5-year lag(P＜0.05).The CI for the hospital admissions fell by 0.014 immediately after the DRG/DIP payment reform and by 0.012 per year thereafter(P＜0.001).Conclusion:BMI reforms not only can contribute to improve the health service utilization and resources,but also it can also improve health equity.In addition,it has a lagged effect on improving health equity.

Objective:To analyze the impact of the universal coverage,integration and DRG/DIP payment method reform of Basic Medical Insurance(BMI)on the equity of the health service utilization and resource allocation.Methods:The 1998-2022 panel data on health service utilization and resources were collected for China.Health equity is measured using the Concentration Index(CI)and Theil index,and the impact of BMI reform on health equity is analyzed by BP neural network and ITSA.Results:Universal coverage,integration,and DRG/DIP payment reform of BMI had a positive effect on the number of health workers,beds,and admissions(P＜0.001),and inhibited the growth of per capita hospitalization costs(P＜0.05).The CI for the number of health workers and beds declined by 0.004 and 0.003 per year after universal coverage of BMI;and both still declined by 0.002 per year with a 5-year lag(P＜0.05).The CI for the hospital admissions fell by 0.014 immediately after the DRG/DIP payment reform and by 0.012 per year thereafter(P＜0.001).Conclusion:BMI reforms not only can contribute to improve the health service utilization and resources,but also it can also improve health equity.In addition,it has a lagged effect on improving health equity.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Objective To investigate the mechanism by which blue light irradiation-activated microglia mediate immune cell recruitment and exacerbate retinal damage,and to explore the role of microglial depletion in inhibiting immune infiltration and protecting the retina.Methods SPF-grade C57BL/6J mice were randomly divided into control group,blue light irradiation group,and PLX5622 pretreatment blue light irradiation group.A retinal injury model was established by continuous LED blue light irradiation for 2 days.In the PLX5622 pretreatment group,microglia were specifically depleted before blue light irradiation.After modeling,HE staining and OCT examination were used to examine retinal histomorphological changes;ERG examination was performed to evaluate retinal function;DHE staining and RT-qPCR were used to detect oxidative stress and inflammatory responses,and Iba1,CD68,CD11b immunofluorescence staining and flow cytometry were used to analyze microglial activation status and immune cell infiltration.Results After blue light irradiation,the retinal outer nuclear layer thickness was significantly reduced;ERG a-wave and b-wave amplitudes decreased;expression of oxidative stress-related genes Nrf2,Sod2,and HO-1 was upregulated;expression of inflammatory factors IL-1β,TNF-α,and ICAM-1 increased;the number of Iba1-positive microglia increased and migrated extensively to the outer nuclear layer;the proportion of CD68+cells and CD11b+immune cells was elevated;and activated microglia aggregated around blood vessels to mediate immune cell infiltration.After PLX5622 pretreatment to deplete microglia,immune cell infiltration was significantly reduced;inflammatory responses were alleviated;retinal structural damage was markedly improved,and visual function was protected.Conclusions Blue light irradiation activates microglia and promotes their migration to the injury area.Activated microglia mediate immune cell recruitment and infiltration,exacerbating retinal inflammatory damage.Microglial depletion can effectively inhibit immune infiltration,rescue retinal structure and function,and provide new therapeutic strategies for the prevention and treatment of blue light-related ocular diseases.