BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

OBJECTIVE: To investigate the short-to-medium-term clinical efficacy of total hip arthroplasty(THA) with Pinnacle ES constrained liner in the treatment of femoral neck fractures(FNF) associated with lower limb neuromuscular disorders. METHODS: A retrospective analysis was conducted on 16 patients who underwent primary THA using Pinnacle ES constrained liner for FNF with lower limb neuromuscular disorders and had complete follow-up data, treated between January 2020 and January 2023. There were 7 males and 9 females, with a mean age of (68.42±3.58) years old ranging from 61 to 75 years old. Among them, 10 cases had left-sided fractures and 6 had right-sided fractures;based on the Garden classification, 11 cases were type Ⅲ and 5 cases were type Ⅳ. The affected limbs were complicated with sequelae of poliomyelitis (2 cases), Parkinson's disease (2 cases), and sequelae of cerebral infarction (12 cases). All operations were performed via a posterolateral approach. Prosthesis position was evaluated using imaging data. Hip function was assessed by the Harris hip score(HHS) and Merle D'Aubigne hip score. During the follow-up period, the occurrence of complications such as prosthetic dislocation, loosening, and infection was recorded. RESULTS: One patient died of advanced tumor 2 years after surgery, and the remaining 15 patients were followed up for 24 to 64 months with a mean of (34.8±5.5) months. The operation time ranged from 50 to 90 minutes with a mean of (75.56±8.15) minutes, and the blood loss ranged from 150 to 200 ml with a mean of (170.32±12.56) ml. All patients achieved primary wound healing after surgery. Intraoperatively, femoral calcar splitting occurred in 2 cases, which were treated with titanium cable binding;no neurovascular injuries were observed in any case. The mean HHS increased from (18.95±2.25) preoperatively to (88.02±2.42) at the last follow-up, and the mean Merle D'Aubigne Score increased from (3.05±0.06) preoperatively to (16.65±0.93) at the last follow-up. Postoperative follow-up X-rays showed good prosthetic position, and no complications such as dislocation, prosthetic loosening, periprosthetic fracture, or deep infection occurred during the follow-up period. CONCLUSION Total hip arthroplasty with Pinnacle ES constrained liner is effective in the treatment of femoral neck fractures associated with lower limb neuromuscular disorders. It can significantly improve hip function, reduce the postoperative prosthetic dislocation rate, provide good initial stability, and achieve satisfactory short-to-medium-term clinical efficacy.
Humans ; Male ; Female ; Middle Aged ; Aged ; Arthroplasty, Replacement, Hip/methods* ; Femoral Neck Fractures/complications* ; Retrospective Studies ; Neuromuscular Diseases/surgery* ; Lower Extremity ; Treatment Outcome

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.

Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

Objective To evaluate the resuscitation efficacy of novel lyophilized platelets(LP,thrombin-stimulated platelets)combined with lactated Ringer's(LR)solution in rabbits with hemorrhagic shock and seawater immersion.Methods Fifty rabbits were randomly assigned to 5 groups(Groups A,B,C,D and E,n=10).After all rabbits were anesthetized with 3%pentobarbital sodium at a dose of 1 mL/kg,soft tissue injury was inflicted in the left lower limb.The blood loss from the soft tissue injury was quantified after gauze hemostasis.The right lower limb was subjected to femoral artery catheterization,followed by blood withdrawal equivalent to 26%of the total blood volume of the rabbit.The rabbits were then vertically immersed in 3%artificial seawater,with the water level reaching above the xiphoid process,and were retrieved in 15 min later.Resuscitation strategies were applied to the rabbits from different group:Group A(no resuscitation),Group B(resuscitation with LR solution),Group C(resuscitation with LR solution and fresh platelets),Group D(resuscitation with LR solution and LP),and Group E(resuscitation with LR solution and novel LP).Coagulation function test,routine blood test,blood gas analysis,and thromboelastography were conducted at baseline and at 1,2 and 4 h after injury.Results The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared.At 1 h after injury,the mean arterial pressure(MAP)of Groups C,D and E(infused with platelet preparations)was significantly higher than that of Group A(without resuscitation,P<0.05);the lactate(Lac)content of Group C was obviously lower than that of Groups A and B(P<0.05);the base excess(BE)and blood urea nitrogen(BUN)levels of Groups C,D and E were notably lower than those of Groups A and B(P<0.05);and the prothrombin time(PT)of Group A was significantly longer than that of before injury(P<0.05).At 2 h after injury,the MAP of Groups C and D was significantly higher than that of Groups A and B,and that of Group E was notably higher than that of Group A(P<0.05);the Lac content of Groups C and E was obviously lower than that of Groups A and B,while that of Group D was also lower than that of Group A(P<0.05);the BE and BUN levels of Groups C,D and E were remarkably lower than those of Groups A and B(P<0.05);the maximum amplitude(MA)value of Group C was higher than that of Group A,while the value of Groups A and D at this time was significantly lower than the corresponding value before injury(P<0.05);and the activated partial clotting time(APTT)of Groups A and D was statistically longer than the corresponding baseline time(P<0.05).At 4 h after injury,the MAP of Groups C,D,and E was higher than that of Groups A and B,and that of Group B was higher than that of Group A(P<0.05);the Lac and BUN levels of Groups C,D,and E were lower than those of Groups A and B(P<0.05);the BE level of Groups C and D were lower than those of Groups A and B(P<0.05);the MA value of Groups B,C,and E were higher than those of Group A(P<0.05),while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values(P<0.05).Conclusion For rabbits with hemorrhagic shock and seawater immersion,the novel LP combined with LR solution can significantly increase the MAP level,reduce Lac content,and sustainably maintain blood clot firmness and coagulation function.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

AIM:To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in hypoxia-induced autophagy and apopto-sis in endothelial cells.METHODS:Human umbili-cal vein endothelial cells(HUVECs)were exposed to hypoxia(1％O2)for varying durations(0,6,12,24 h)to evaluate autophagy and apoptosis levels.LOX-1 was further intervened to explore its effects on autophagy and apoptosis.GFP-LC3B adenovirus in-fection was observed under fluorescence microsco-py to assess LC3B expression.Autophagosomes were detected by transmission electron microscopy(TEM).LOX-1 mRNA levels were measured using re-al-time PCR.Protein expression of LOX-1,LC3Ⅱ/Ⅰ,Beclin-1,Atg5,cleaved-caspase 3,Bax,and Bcl-2 was analyzed by Western blot.Reactive oxygen spe-cies(ROS)levels were quantified using the DCFH-DA fluorescent probe.Apoptosis was assessed via Hoechst staining and flow cytometry(Annexin V-PI double staining).RESULTS:Hypoxia(1％O2,24 h)significantly increased LC3Ⅱ puncta under fluores-cence microscopy,upregulated LC3Ⅱ/Ⅰ protein ex-pression,and induced autophagosome formation observed by TEM.Hypoxia elevated ROS produc-tion and promoted apoptosis.LOX-1 mRNA and protein expression were upregulated in hypoxic HU-VECs.LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy,downregulating au-tophagy-related proteins(Beclin-1,Atg5,LC3Ⅱ/Ⅰ).LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis,as evidenced by decreased ex-pression of cleaved-caspase 3 and Bax,and in-creased Bcl-2 levels.CONCLUSION:Hypoxia in-duced upregulation of LOX-1 expression to produce ROS,thereby promoting autophagy and apoptosis in endothelial cells.