OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted cultivated Astragali Radix（CA） and wild-simulated Astragali Radix（WA） from the aspects of character， microstructure and chemical composition by modern technological means. MethodThe collected CA and WA were compared in characters and microscopic characteristics in cross section， and comparative analysis were performed on the contents of cellulose， extracts， carbohydrate， total flavonoids， total saponins， etc. Then ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometer（UPLC-Q-TOF-MS） and desorption electrospray ionization mass spectrometry imaging（DESI-MSI） were used to comparatively analyze the secondary metabolites and their spatial distributions in the xylem and phloem of CA and WA. ResultIn terms of characters， the characters and sectional features of WA was consistent with the characteristics of high-quality Astragali Radix， while the CA was quite different from the traditional high-quality Astragali Radix. In terms of microscopy， the phellem layer of CA was thin， and the section fissures were mostly distributed through the cambium in a long strip shape without obvious growth ring characteristics. The cork layer of WA was thick， and the cracks in the section were distributed in the center of the xylem and the outer edge of the phloem in an irregular cavity shape. The cambium was tight without cracks， and had obvious characteristics of a growth ring. In terms of chemical composition， the contents of water-soluble extract， 80% ethanol extract and sucrose of CA was significantly higher than those of WA， while the contents of total saponins， lignin and hemicellulose were significantly lower than those of WA. And the contents of 100% ethanol extract， total polysaccharides and total flavonoids in both of them were generally similar， but slightly higher in WA. The contents of 2 kinds of monoacyl-substituted flavonoid glycosides in the xylem of WA was significantly higher than those of CA， while the contents of 2 kinds of flavonoid aglycones and one flavonoid glycoside were on the contrary. The contents of 7 saponins in phloem of WA were significantly higher than those of CA. ConclusionThere are significant differences between CA and WA in characters， microstructure and chemical components， in which CA has a fast growth rate and a short planting period， and the primary metabolites such as water-soluble extracts and sucrose are more enriched， which is the reason for its firm texture and sweetness being significantly higher than those of WA. However， the contents of lignin， hemicellulose and some secondary metabolites in WA are significantly higher than those in the CA， which are close to the traditional description of characters and quality. Based on the results of this study， it is suggested to strengthen the production of WA， improve the supply capacity of WA， and gradually upgrade the current standard. It is recommended to increase the contents of monoacyl-substituted flavonoid glycosides， total saponins and other indicators that can characterize different production methods， so as to guide the high-quality production of Astragali Radix.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective To observe the manifestations of adult adrenal glands in intraoperative ultrasound(IOUS).Methods A total of 71 patients who underwent surgery for liver,biliary or pancreatic lesions were enrolled.Adrenal glands manifestations in IOUS were observed,and the displaying rate and the measured thickness of adrenal glands of IOUS were compared with those of CT/MRI.Results Adult adrenal gland manifested as bilateral weak echogenic structures with clear boundary and irregularly shape in IOUS.CT/MRI displaying rate of adrenal gland was 97.18％(138/142),of IOUS was 95.07％(135/142).IOUS displaying rate of the left side adrenal gland was 97.18％(69/71),of the right side adrenal gland was 92.96％(66/71),including 4 adrenal glands not shown on CT/MRI.The thickness of adrenal gland measured with IOUS was greater than those with CT/MRI(all P＜0.05).Conclusion IOUS of Adult adrenal glands present as bilateral weak echogenic structures with clear boundary and irregularly shape.IOUS displaying rate of adult adrenal gland was higher of the left side than the right side.

Objective To analyze and compare the clinical efficacy of CalliSpheres drug-eluting micro-spheres and blank microspheres in the treatment of advanced non-small cell lung cancer by bronchial arterial chemoembolization.Methods Fifty patients with advanced non-small cell lung cancer who had failed or relapsed after radiotherapy,chemotherapy,targeting and immunotherapy were collected and treated with super-selective bronchial artery chemoembolization.A retrospective analysis was conducted to compare the tumor response rate and survival between CalliSpheres drug-eluting and blank microspheres.Results The PR,ORR and DCR in the drug-eluted microsphere group were higher than those in the blank microsphere group,and there was a statistical difference in DCR between the two groups 1 month after surgery(χ2 = 4.08,P = 0.04).PD in the drug-eluted microsphere group was lower than that in the blank microsphere group.The CEA,CYF and SCC in the drug-eluted microsphere group after surgery were lower than those in the blank microsphere group,and the CEA,CYF and SCC in the two groups after surgery were lower than those before surgery,and there were statistical differences in CEA and CYF 1 month after surgery between the two groups.The PFS and OS in drug-eluted microsphere group were higher than those in blank microsphere group.Conclusion CalliSpheres drug-eluting microspheres could improve the effective rate of tumor treatment and prolong the survival time more effectively than the blank micro-spheres via arterial chemoembolization,providing reliable clinical practice basis for the treatment of advanced non-small cell lung cancer.

Objective:To explore the development and interaction between chronotype and depressive symp-toms among middle school students in Chongqing.Methods:A total of 1208 middle school students(613 in grade 7,595 in grade 10)were surveyed for three follow-ups at 6-month intervals.Periods T1-T3 represented baseline,6 months later,and 12 months later,respectively.Chronotype and depressive symptoms were measured by the Morn-ing and Evening Questionnaire-5(MEQ-5)and the Patient Health Questionnaire-9(PHQ-9).Analyses were per-formed using SPSS 26.0 and Mplus 8.3.Results:The MEQ-5 scores were lower in T1 than in T3,and the scores were lower in T2 than in T1 and T3(F=20.08,P＜0.001),suggesting a fluctuating trend of chronotype shifting to the Evening-type first after baseline and then to the Morning-type.The PHQ-9 scores exhibited a significant differ-ence among the three-time measurements(x2/df=9.77/2,P＜0.01).But pairwise comparisons did not yield any statistically significant findings(P＞0.05).The cross-lagged panel model showed that pathways of Ti MEQ-5 scores negatively predicted Ti+1 PHQ-9 scores(βTi-Ti+1=-0.12/-0.09,P＜0.05)and TiPHQ-9 scores nega-tively predicted Ti+1 MEQ-5 scores(βTi-Ti+1=-0.07/-0.11,P＜0.05).Conclusion:Chronotype and depressive symptoms show some changes in adolescents.The more inclined adolescents are to the Evening-type,the higher the likelihood of depressive symptoms occurring later.The more severe the depressive symptoms,the greater the likeli-hood of a subsequent shift to the Evening-type.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

Objective To explore the monitoring frequency and safety of coagulation function in patients with deep venous thrombosis(DVT)catheter directed thrombolysis during thrombolysis.Methods From January 2014 to December 2021,a total of 246 patients with DVT catheter directed thrombolysis in the hospital were selected as the research objects.According to the monitoring frequency of coagulation function,they were di-vided into group A(160 patients were monitored every 24 hours)and group B(86 patients were monitored every 12 hours).The medication regimen,clinical efficacy,bleeding complications and the time trend of coagu-lation function monitoring were compared between the two groups.Results There were no significant differ-ences in urokinase dosage[240(160,320)million U vs.210(160,270)million U]and the clinical efficacy(88.12％vs.88.37％)in group A and group B(P＞0.05).The incidence of minor bleeding in group A was lower than that in group B(15.62％vs.27.91％),with statistical significance(P＜0.05).There was no sta-tistical difference between group A and group B in the changes of D-dimer,fibrinogen and activated partial thromboplastin time with time(P＞0.05).Compared with the change of platelet(PLT)with time in group A and group B,the difference was statistically significant(P＜0.05).Conclusion The overall change trend of coagulation function with monitoring frequency every 24 or 12 hours is consistent,and monitoring coagulation function once every 24 hours will not increase the risk of bleeding.

Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oil-water partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.