Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.

Objective To explore the relationship of metabolic comorbidities and insulin resistance(IR)with chronic kidney disease(CKD)among elderly individuals undergoing health exam.Methods A cross-sectional observational study was conducted on 8358 older adults who took health exam in Chinese PLA General Hospital between December 2009 and May 2021.According to the guidelines for CKD diagnostic criteria,they were divided into CKD group(983 cases)and non-CKD(7375 cases).Clinical data was collected,and the eGDR was calculated.Quasi-Bayesian method was used for causal mediation analysis.Results The prevalence of metabolic comorbidi-ties including hypertension,CHD,DM,hyperlipidemia,and hyperuricemia was significantly higher in the CKD group than the non-CKD group(P＜0.01).The eGDR was obviously lower in the CKD group than the non-CKD group[6.88±2.09 mg/(kg·min)vs 8.41±2.12 mg/(kg·min),P＜0.01].Logistic regression analysis revealed that,without adjusting covariates,each 1-unit increase in eGDR was associated with a 29％reduction in the risk of developing CKD(OR=0.714,95％CI:0.691-0.738,P＜0.01),and after adjusting covariates,eGDR remained signifi-cantly negatively association with the risk of CKD(P＜0.01).Mediation analysis indicated that DM and brachial-ankle pulse wave velocity accounted for the highest proportions of the mediating effect in the relationship between eGDR and CKD(14.2％and 12.5％,respectively).Conclusion In the elderly population undergoing health exam,reduced insulin sensitivity is significantly asso-ciated with the development of CKD.Diabetes and arteriosclerosis exert mediating effect in this association.

Objective:To investigate the effects of melatonin(Mel)on inflammatory damage in the retina of rats with oxygen-induced retinopathy(OIR)and the molecular mechanisms.Methods:Healthy neonatal SD rats were di-vided into the sham group(Sham),the model group(OIR),and the melatonin treatment group(OIR+Mel).The OIR model was induced by alternating 50%/10%oxygen concentration exposure for 14 d.The OIR+Mel group was in-jected intraperitoneally with 10 mg-kg-1 melatonin.Hematoxylin-eosin(HE)staining was used to observe the morpho-logical changes in the retinal tissue;immunohistochemical staining was used to detect the expression of retinal cleaved-caspase-1 and IL-1β proteins;and immunofluorescence staining was used to detect the expression of cGAS-STING-NL-RP3 signaling molecules and gasdermin(GSDMD)in the microglia of the retina.Results:HE staining results showed that compared with the Sham group,the retinal cells in the OIR group were disorganized and the thickness of the inner retina was significantly thinner,and the retinal cells in the OIR+Mel group were more neatly arranged compared with those in the OIR group(P<0.05).Immunohistochemical staining results showed that the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR+Mel group decreased signifi-cantly compared with that of the OIR group(P<0.05).Immunofluorescence staining results showed that the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR+Mel group de-creased significantly compared with that in the OIR group(P<0.05);The number of Iba-1+/N-GSDMD+cells in-creased significantly in the OIR group compared with the Sham group,whereas the number of Iba-1+/N-GSDMD+cells in the OIR+Mel group was significantly less than that in the OIR group,but still more than that in the Sham group(P<0.05).Conclusion:Mel inhibits the pyroptosis of retinal microglia,thus attenuates retinal inflammatory injury in OIR rats,and its mechanism may be related to the cGAS-STING-NLRP3 signaling pathway.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.

Objective To investigate the relationship between calcium-sensing receptor(CaSR)gene rs17251221,rs60388563 loci polymorphisms and the genetic susceptibility of breast cancer(BC).Methods A total of 122 patients with breast cancer admitted to Hengshui Second People's Hospital from January 2022 to June 2024 were selected as the BC group,and 100 healthy women without blood relationship at the same time were selected as the control group.The polymorphisms of CaSR gene rs17251221,rs60388563 loci were detected by polymerase chain reaction(PCR).The clinical data,genotype distribution and allele frequency were compared between the two groups.Non-conditional Logistic regression model was used to analyze the correlation between CaSR gene polymorphism and genetic susceptibility of BC patients.Results Comparing the general data of the two group,the proportion of family history of cancer in the BC group was significantly higher than that in the control group,and the difference was statistically significant(t=12.246,P<0.05).The genotype distribution of CaSR gene rs17251221 and rs60388563 loci in the control group and the BC group was consistent with the Hardy-Weinberg equilibrium law(χ2=0.087～1.202,P＞0.05),which was representative of the population.Under the co-dominant model of rs17251221 and rs60388563 loci,the risk of BC in GG genotype was significantly increased(OR=1.493,95%CI=1.070～2.108;OR=1.483,95%CI=1.034～2.121).Under the dominant model(AA vs GA+GG)and recessive model(GG vs GA+AA),the rs17251221 locus carrying G allele(OR=1.371,95%CI=1.023～1.824)and A allele(OR=0.524,95%CI=0.221～0.926)was significantly associated with the risk of BC(P<0.05).Under the dominant model(CC vs GC+GG)and recessive model(GG vs GC+CC),the rs60388563 locus carrying G allele(OR=1.245,95%CI=1.107～1.461)and C allele(OR=0.682,95%CI=0.523～0.974)was significantly associated with the risk of BC(P<0.05).Conclusion The rs17251221,rs60388563 loci polymorphisms of CaSR gene are closely related to BC susceptibility,and the risk of BC is high in individuals carrying G allele.

Objective:To investigate the effects of melatonin(Mel)on inflammatory damage in the retina of rats with oxygen-induced retinopathy(OIR)and the molecular mechanisms.Methods:Healthy neonatal SD rats were di-vided into the sham group(Sham),the model group(OIR),and the melatonin treatment group(OIR+Mel).The OIR model was induced by alternating 50%/10%oxygen concentration exposure for 14 d.The OIR+Mel group was in-jected intraperitoneally with 10 mg-kg-1 melatonin.Hematoxylin-eosin(HE)staining was used to observe the morpho-logical changes in the retinal tissue;immunohistochemical staining was used to detect the expression of retinal cleaved-caspase-1 and IL-1β proteins;and immunofluorescence staining was used to detect the expression of cGAS-STING-NL-RP3 signaling molecules and gasdermin(GSDMD)in the microglia of the retina.Results:HE staining results showed that compared with the Sham group,the retinal cells in the OIR group were disorganized and the thickness of the inner retina was significantly thinner,and the retinal cells in the OIR+Mel group were more neatly arranged compared with those in the OIR group(P<0.05).Immunohistochemical staining results showed that the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR+Mel group decreased signifi-cantly compared with that of the OIR group(P<0.05).Immunofluorescence staining results showed that the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR+Mel group de-creased significantly compared with that in the OIR group(P<0.05);The number of Iba-1+/N-GSDMD+cells in-creased significantly in the OIR group compared with the Sham group,whereas the number of Iba-1+/N-GSDMD+cells in the OIR+Mel group was significantly less than that in the OIR group,but still more than that in the Sham group(P<0.05).Conclusion:Mel inhibits the pyroptosis of retinal microglia,thus attenuates retinal inflammatory injury in OIR rats,and its mechanism may be related to the cGAS-STING-NLRP3 signaling pathway.

Background and purpose:As one of the first-line treatment methods for differentiated thyroid cancer(DTC),131I treatment is an important therapeutic approach for most patients with medium-high recurrence risk DTC after total or near-total thyroidectomy.Risk stratification and real-time dynamic assessment before 131I treatment after surgery are important steps in deciding on 131I treatment,enabling individualized treatment.This retrospective study aimed to explore the role of diagnostic whole body scan(DxWBS)in the decision-making of treatment for DTC after surgery and before 131I therapy.Methods:DTC patients who underwent pre-ablation evaluation were included.Patients were divided into low,medium and high sTg groups based on their pre-131I treatment stimulated thyroglobulin(sTg)levels(＜1 ng/mL,1 ng/mL≤sTg＜10 ng/mL,sTg≥10 ng/mL).The concordance rates of DxWBS and post treatment whole body scan(RxWBS)in each patient of the whole cohort were compared.The lesion detection rate between DxWBS and RxWBS in different sTg level groups was also explored.The"thyroid stunning effect"by DxWBS was evaluated by RxWBS.Through these analyses,the role of DxWBS in 131I treatment decision-making and its predicting treatment objectives were assessed.This study was approved by the Ethics Committee of Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences(ethics number:JS-2151).Results:A total of 91 patients were included.The low,medium and high sTg groups accounted for 15.4%(14/91),34.1%(31/91)and 50.5%(46/91)of the patients,respectively.Comparison of DxWBS and RxWBS results in the same patients in each sTg group showed no evidence of a stunning effect on 131I treatment.The overall concordance rate between DxWBS and RxWBS was 89.0%(81/91);In different sTg level groups was 100.0%(14/14),90.3%(28/31),84.8%(39/46)respectively.Taking sTg levels into consideration,DxWBS accurately predicted the need for total thyroidectomy,with a 100%(20/20)agreement with RxWBS.Among the 71 patients who received adjuvant therapy and/or remnant ablation due to suspected elevated Tg or high recurrence risk stratification or the iodine-avid metastatic lesions identified by DxWBS,87.5%(63/71)showed only residual thyroid tissue by DxWBS;Through the purpose verification by RxWBS and single photon emission computed tomography(SPECT)/CT,only 12.7%(9/71)of cases were verified as adjuvant or tumoricidal treatment due to iodine-avid cervical lymph node and/or lung metastasis identified by RxWBS,87.3%(62/71)were residual thyroid ablation.In the medium and high sTg group,the overall detection rate of functional cervical lymph node metastasis by DxWBS and RxWBS was 5.5%(5/91).For the detection of functional lung metastases,the overall detection rate of DxWBS was slightly lower than that of RxWBS(3.3%vs 5.5%).This indicates that DxWBS can be used to accurately pre-judge the purposes of 131I treatment,particularly for thyroid ablation and adjuvant therapy.Conclusion:DxWBS did not induce"thyroid stunning"effect.Integrating DxWBS as a theranostic tool into the real-time decision-making and evaluation system of 131I treatment,as well as with sTg and other biochemical indicators,may help to bridge the limitations of static evaluations based on pathology and clinical data,and provides a clear understanding and more precise objectives of 131I treatment.

BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.

Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.