AIM:This study investigated the potential mechanism of acupuncture regulating adenosine A1 re-ceptor(ADORA1)in the mouse caudate putamen(CPu)to improve neuroplasticity and alleviate inflammatory pain.METHODS:Male C57BL/6 mice were randomly divided into five groups,namely,saline,complete Freund's adjuvant(CFA),acupuncture(MA),acupuncture+ADORA1 shRNA(MA+shRNA),and acupuncture+negative shRNA(MA+NCshRNA)groups.Twenty-one days before modeling,the mice in the MA+shRNA and MA+NCshRNA groups were in-jected with ADORA1 shRNA and control virus into the CPu.Modeling was performed 21 d later by injection of CFA into the right plantar skin of mice in the model and acupuncture groups to induce adjuvant-mediated arthritis.On day 2 after modeling,mice in the acupuncture groups received acupuncture at bilateral"Zusanli"points,30 min per session,once a day,for a total of 7 days.The paw thermal radiation pain threshold was used as an indicator of the effects on pain in the mice.Changes in the protein levels of ADORA1,synaptophysin(SYP),synapsin(SYN)I,SYN II,and brain-derived neurotrophic factor(BDNF)in the CPu were assessed by Western blot,and transmission electron microscopy was used to examine the dendritic structure and synaptic ultrastructure of neurons within the CPu.RESULTS:(1)Compared with the saline group,CFA modeling significantly reduced the thermal radiation pain threshold in mice(P<0.01),as well as the protein levels of ADORA1(P<0.01).Compared with the CFA group,the thermal pain threshold in the MA group in-creased between days 1 and 7 of acupuncture(P<0.05 or P<0.01),and ADORA1 protein levels increased(P<0.01).(2)Compared with the saline group,SYN I,SYN II,and BDNF protein levels were increased in the CFA group(P<0.05 or P<0.01),while relative to the CFA group,the levels of SYN I,SYN II,and BDNF were reduced in the acupuncture group(P<0.05 or P<0.01).No significant changes in SYP protein levels were observed in any of the groups.(3)Golgi staining and Sholl analysis showed that compared with the saline group,there were reductions in the total dendritic length and number of intersection points in the CFA group,while the dendritic spine density increased(P<0.05).Relative to the CFA group,the total dendritic length and the number of intersection points were increased in the MA group,while the dendritic spine density decreased(P<0.05).(4)Transmission electron microscopy revealed that compared with the Sa-line group,the synaptic clefts were narrower in the CFA group,while the density of synaptic vesicles in the presynaptic membrane was increased.Compared with the CFA group,synaptic clefts in the MA group were wider,and synaptic vesi-cle densities in the presynaptic membrane were reduced.(5)Twenty-one days after viral transfection,the thermal pain threshold in the MA and MA+NCshRNA groups increased from day 1 to day 7 of acupuncture relative to the CFA and MA+shRNA groups(P<0.05 or P<0.01),while the expression of ADORA1 was increased in both the MA and MA+NCshRNA groups(P<0.05 or P<0.01).(6)Compared with the CFA and MA+shRNA groups,the protein expression of SYN II and BDNF in the MA and MA+NCshRNA groups was reduced(P<0.05 or P<0.01).No significant changes in SYN I protein were observed in any of the groups.CONCLUSION:Acupuncture on Zusanli point can alleviate chronic pain in CFA-treated mice,potentially mediated by up-regulation of ADORA1 expression in the CPu brain region,thereby improving neuroplasticity.

Chronic pain has emerged as a prevalent medical challenge in contemporary society.Patients suffering from chronic pain frequently develop comorbid psychological disorders,including anxiety,depression,post-traumatic stress disorder,and various psychiatric syndromes.These psychological complications not only affect patients' pain perception and responses,but may also constitute critical obstacles during pain management interventions.Acupuncture is a long-established clinical practice that has demonstrated remarkable efficacy in alleviating diverse pain types and has shown favorable therapeutic outcomes in ameliorating emotional disturbances such as anxiety and depression.The precise mechanisms underlying acupuncture-induced analgesia and anxiolytic effects,however,remain to be fully elucidated.In this context,it is essential to establish suitable and stable animal models to allow in-depth investigations into the pathogenesis of pain-related emotional disorders and the mechanistic foundations of acupuncture.This article presents a comprehensive review of recent literature regarding the selection of experimental animals,model-establishment method ologies,and behavioral-assessment paradigms pertaining to animal model platforms of chronic pain with comorbid anxiety.We also provide an in-depth discussion of research advancements regarding acupuncture intervention parameters,including needling techniques,acupoint selection,treatment duration,and efficacy evaluation within these animal models.This review proposes comprehensive and reference strategies for constructing preclinical animal models to investigate the mechanisms of acupuncture in managing chronic pain with comorbid anxiety,thus supporting scientific advancements in related research fields.

AIM:This study investigated the potential mechanism of acupuncture regulating adenosine A1 re-ceptor(ADORA1)in the mouse caudate putamen(CPu)to improve neuroplasticity and alleviate inflammatory pain.METHODS:Male C57BL/6 mice were randomly divided into five groups,namely,saline,complete Freund's adjuvant(CFA),acupuncture(MA),acupuncture+ADORA1 shRNA(MA+shRNA),and acupuncture+negative shRNA(MA+NCshRNA)groups.Twenty-one days before modeling,the mice in the MA+shRNA and MA+NCshRNA groups were in-jected with ADORA1 shRNA and control virus into the CPu.Modeling was performed 21 d later by injection of CFA into the right plantar skin of mice in the model and acupuncture groups to induce adjuvant-mediated arthritis.On day 2 after modeling,mice in the acupuncture groups received acupuncture at bilateral"Zusanli"points,30 min per session,once a day,for a total of 7 days.The paw thermal radiation pain threshold was used as an indicator of the effects on pain in the mice.Changes in the protein levels of ADORA1,synaptophysin(SYP),synapsin(SYN)I,SYN II,and brain-derived neurotrophic factor(BDNF)in the CPu were assessed by Western blot,and transmission electron microscopy was used to examine the dendritic structure and synaptic ultrastructure of neurons within the CPu.RESULTS:(1)Compared with the saline group,CFA modeling significantly reduced the thermal radiation pain threshold in mice(P<0.01),as well as the protein levels of ADORA1(P<0.01).Compared with the CFA group,the thermal pain threshold in the MA group in-creased between days 1 and 7 of acupuncture(P<0.05 or P<0.01),and ADORA1 protein levels increased(P<0.01).(2)Compared with the saline group,SYN I,SYN II,and BDNF protein levels were increased in the CFA group(P<0.05 or P<0.01),while relative to the CFA group,the levels of SYN I,SYN II,and BDNF were reduced in the acupuncture group(P<0.05 or P<0.01).No significant changes in SYP protein levels were observed in any of the groups.(3)Golgi staining and Sholl analysis showed that compared with the saline group,there were reductions in the total dendritic length and number of intersection points in the CFA group,while the dendritic spine density increased(P<0.05).Relative to the CFA group,the total dendritic length and the number of intersection points were increased in the MA group,while the dendritic spine density decreased(P<0.05).(4)Transmission electron microscopy revealed that compared with the Sa-line group,the synaptic clefts were narrower in the CFA group,while the density of synaptic vesicles in the presynaptic membrane was increased.Compared with the CFA group,synaptic clefts in the MA group were wider,and synaptic vesi-cle densities in the presynaptic membrane were reduced.(5)Twenty-one days after viral transfection,the thermal pain threshold in the MA and MA+NCshRNA groups increased from day 1 to day 7 of acupuncture relative to the CFA and MA+shRNA groups(P<0.05 or P<0.01),while the expression of ADORA1 was increased in both the MA and MA+NCshRNA groups(P<0.05 or P<0.01).(6)Compared with the CFA and MA+shRNA groups,the protein expression of SYN II and BDNF in the MA and MA+NCshRNA groups was reduced(P<0.05 or P<0.01).No significant changes in SYN I protein were observed in any of the groups.CONCLUSION:Acupuncture on Zusanli point can alleviate chronic pain in CFA-treated mice,potentially mediated by up-regulation of ADORA1 expression in the CPu brain region,thereby improving neuroplasticity.

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

Chronic pain has emerged as a prevalent medical challenge in contemporary society.Patients suffering from chronic pain frequently develop comorbid psychological disorders,including anxiety,depression,post-traumatic stress disorder,and various psychiatric syndromes.These psychological complications not only affect patients' pain perception and responses,but may also constitute critical obstacles during pain management interventions.Acupuncture is a long-established clinical practice that has demonstrated remarkable efficacy in alleviating diverse pain types and has shown favorable therapeutic outcomes in ameliorating emotional disturbances such as anxiety and depression.The precise mechanisms underlying acupuncture-induced analgesia and anxiolytic effects,however,remain to be fully elucidated.In this context,it is essential to establish suitable and stable animal models to allow in-depth investigations into the pathogenesis of pain-related emotional disorders and the mechanistic foundations of acupuncture.This article presents a comprehensive review of recent literature regarding the selection of experimental animals,model-establishment method ologies,and behavioral-assessment paradigms pertaining to animal model platforms of chronic pain with comorbid anxiety.We also provide an in-depth discussion of research advancements regarding acupuncture intervention parameters,including needling techniques,acupoint selection,treatment duration,and efficacy evaluation within these animal models.This review proposes comprehensive and reference strategies for constructing preclinical animal models to investigate the mechanisms of acupuncture in managing chronic pain with comorbid anxiety,thus supporting scientific advancements in related research fields.

Objective:To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration.Methods:A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson′s correlation to assess the relationship between MAA and degree of hearing loss.Results:MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss ( r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration ( F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions:The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.

Objective To observe the effects of different frequencies of electroacupuncture on the degree of atrophy of quadriceps femoris in rabbits with anterior cruciate ligament(ACL)injury model;To explore the possible mechanisms of electroacupuncture in treating ACL injury.Methods Totally 24 New Zealand rabbits were randomly divided into blank group,model group,low-frequency electroacupuncture group and high-frequency electroacupuncture group,with 6 rabbits in each group.Except for the blank group,ACL injury models were established in the other groups.On the 7th day after modeling,the low-frequency electroacupuncture group and the high-frequency electroacupuncture group performed electroacupuncture treatment(continuous wave,frequency of 2 Hz and 100 Hz respectively,and left the needle in place for 20 min)at"Xuehai"and"Liangqiu"of the operation side,and the remaining groups were only grasped and immobilized,for 21 days.The mass ratio of the quadriceps femoris was calculated,the histopathological morphology of the quadriceps femoris tissue of the rabbits in each group was observed by HE staining,the expressions of NO,iNOS in quadriceps femoris tissue were detected by ELISA,the content of ROS in quadriceps femoris tissue was detected by fluorescent probe,the protein expressions of PERK,ATF6,IRE1,MuRF1,MAFbx in quadriceps femoris tissue were detected by Western blot.Results Compared with the blank group,the quadriceps femoris muscle mass ratio of the model group rabbits was significantly reduced(P<0.01),with irregular arrangement of muscle cells,accompanied by swelling and atrophy,significant interstitial edema,and extensive inflammatory infiltration,the contents of NO,iNOS and ROS in quadriceps femoris tissue significantly increased(P<0.01),while the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly increased(P<0.01).Compared with the model group,the quadriceps femoris muscle mass ratio in the low-frequency and high-frequency electroacupuncture groups significantly increased(P<0.01),with regular arrangement of muscle cells,improved swelling and atrophy of cells,and reduced interstitial edema and inflammation,the contents of NO,iNOS and ROS in quadriceps femoris tissue were significantly reduced(P<0.01),and the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly decreased(P<0.01).Moreover,the low-frequency electroacupuncture group had better effects than the high-frequency electroacupuncture group(P<0.05).Conclusion Different frequencies of electroacupuncture intervention in ACL injury rabbits can better delay the degree of quadriceps femoris atrophy,and its mechanism may be related to reducing the expressions of oxidative metabolites NO,iNOS,ROS,and reducing the expressions of endoplasmic reticulum stress-related proteins PERK,ATF6,IRE1 in quadriceps fermoris,which in turn inhibit the expressions of quadriceps atrophy factors MuRF1,MAFbx,and delaying the degradation of quadriceps muscle proteins.The effect of low-frequency electroacupuncture is superior to the high-frequency electroacupuncture.

Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85％)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61％to 46.47％.The 5-year relative survival rate increased from 42.1 8％to 51.11％.The 5-year age-standardized relative survival rate increased from 40.57％to 49.80％.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43％of thyroid cancer was the highest,followed by female breast cancer(88.35％)and corpus uteri cancer(85.56％);5.87％of pancreas cancer was the lowest,followed by gallbladder cancer(13.64％)and oesophagus cancer(17.72％).the rate of lung cancer with the largest number of cases was 23.59％,followed by colorectal cancer(59.82％)and stomach cancer(38.65％).The 5-year relative survival rate of total cases of all sites increased from 40.55％in 2002 to 52.77％in 2013,with an average annual percent change of 2.40％.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.

Objective:To investigate the incidence and mortality of ovarian,fallopian tube and other uterine adnexa cancer in 2016 and their trends during 2002 through 2016 in Shanghai. Methods:Data on new ovarian,fallopian tube and other uterine adnexa cancer diagnoses and deaths during 2002 through 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.The incidence and mortality stratified by year of diagnosis or death,site and age-group were analyzed.The number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.Trends in number,age-specific rate,age-standardized rate and others were estimated.Trends in age-standardized rate of incidence and mortality for the ovarian cancer were estimated by Joinpoint analysis and characterized by the annual percent change(APC).The number and proportion of selected indexes of diagnostic characteristics of new ovarian and fallopian tube cancer cases were also calculated.Segi's 1960 world standard population was used for calculating age-standardized rates. Results:The new uterine adnexa cancer cases and deaths were 813 and 440 in Shanghai in 2016.There were 751 cases(92.37％)and 419 deaths(95.23％)of ovarian cancer,and 48 cases(5.91％)and 17 deaths(3.86％)of fallopian tube cancer.The crude rate of ovarian cancer incidence was 10.29/105,and the age-standardized rate was 5.33/105.The crude rate of mortality was 5.74/105,and the age-standardized rate was 2.44/105.Overall,the age-specific rates of incidence and mortality increased with aging.They reached the peak at the age group of 55-59 years and 80-84 years,respectively.Joinpoint analyses showed a significant decreasing trend in the standardized incidence of ovarian cancer in Shanghai from 2002 to 2016,with an average annual increase of 1.78％(APC=-1.78,P＜0.001),while the increase in standardized mortality was not statistically significant.The proportion of pathological diagnosis on ovarian cancer increased to 85.02％,and the proportions of stageⅢ and Ⅳ continued to increase.The incidence of ovarian cancer in Shanghai from 2002 to 2016 showed a decreasing trend,while the mortality showed a fluctuating trend. Conclusion:In Shanghai,the age-standardized incidence rate of ovarian cancer was declined steadily,but the proportion of diagnosed advanced increased.The number of fallopian tube cancer cases increased steadily.

Objective:To describe the long-term characteristics and trend changes in the incidence and mortality of female breast cancer in Shanghai from 1 973 to 2017,aiming to provide references for exploring the etiology of breast cancer and formulating strategies and measures for prevention,intervention and control. Methods:Joinpoint software was used to analyze the trend changes in the incidence and mortality of female breast cancer in Shanghai from 1 973 to 2017,and an age-period-cohort model was constructed to explore the effects of age,year of diagnosis,and birth cohort on long-term trend changes. Results:From 1 973 to 2017,there were 68 192 new cases of female breast cancer in Shanghai,with a diagnosed rate of 31.72/100 000.The incidence rate continued to rise,and the risk of the disease continued to rise from the age of 20 years,and the rise rate accelerated significantly after the age of 40 years.There were 21 535 female breast cancer deaths from 1 973 to 2017.The mortality rate was stable,with a death rate of 8.62/100 000,and the risk of death increased significantly from the age of 45 years.The effects of age,period and cohort had a significant impact on the incidence of breast cancer(P＜0.01),while the increase in mortality rate was related to age and cohort effects(P＜0.01). Conclusion:The incidence rate of female breast cancer in Shanghai is still rising rapidly,and the mortality trend is generally stable,suggesting that the treatment is effective and the quality of life is improved.However,breast cancer is still the main malignant tumor among females in Shanghai.It should be continued to implement prevention and control strategies such as lifestyle intervention and screening of high-risk individuals to further strengthen the prevention and control of breast cancer.