Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To investigate the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.Methods Total of 135 patients of extra-articular fractures of the middle and lower third of the tibia from January 2013 to December 2018 were retrospectively analyzed,including 85 males and 50 females,ranged from 19 to 80 years old.All cases were treated with locking plates.The patients were divided into union group and delayed union group ac-cording to the condition of fracture union.The risk factors of delayed healing were determined by univariate analysis of 14 factors that might affect fracture healing first,then the factors with significance were analyzed by binary Logistic regression.Results There were 13 patients of delayed union,and the rate of delayed union was 9.63％.Univariate analysis showed that delayed union was associated with age,smoking,reduction method,anemia and time of preoperative preparation.Regression analysis showed thatage[OR=0.849,95％CI(0.755,0.954),P=0.006],smoking[OR=0.020,95％CI(0.002,0.193),P=0.001],reduction method[OR=23.924,95％CI(2.210,258.943),P=0.009],anemia[OR=0.016,95％CI(0.001,0.289),P=0.005]were the con-tributory factors for delayed union.Conclusion Young age,smoking,closed reduction and anemia are the risk factors for de-layed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.

Objective To observe the clinical efficacy of meridian massage in the treatment of cervical spondylotic radicu-lopathy.Methods Sixty-four patients with cervical radiculopathy treated from March 2020 to June 2023 were divided into the observation group and the treatment group,with 32 cases in each group.The observation group received conventional treat-ment,including 14 males and 18 females with an average age of(41.34±7.23)years old ranging from 32 to 55 years old;the disease duration ranged from 9 to 17 months with an average of(14.23±3.56)months;C5 and C6 nerve root compression oc-curred in 12 cases,C7 nerve root compression occurred in 17 cases,C8 nerve root compression occurred in 3 cases.The treat-ment group received massage therapy on the basis of conventional treatment,including 17 males and 15 females with an aver-age age of(40.86±6.97)years old ranging from 30 to 54 years old;the disease duration ranged from 8 to 18 months with an av-erage of(15.43±3.48)months;C5 and C6 nerve root compression occurred in 14 cases,C7 nerve root compression occurred in 16 cases,C8 nerve root compression occurred in 2 cases.The clinical efficacy was evaluated by visual analogue scale(VAS),neck disability index(NDI)and clinical assessment scale for cervical spondylosis(CASCS)before and after 2-week treatment,and the range of motion of cervical spine was compared before and after treatment.Results After 2-week treatment,the VAS and NDI scores of the treatment group and the observation group decreased,while the CASCS scores increased(P＜0.001).Af-ter 2-week treatment,the VAS and NDI scores were lower and the CASCS scores were higher in the treatment group than those of the observation group(P＜0.001).Comparing with those before treatment,the range of motion of flexion,extension,left flex-ion,right flexion,left rotation and right rotation after 2-week treatment increased in two groups(P＜0.05).Comparing with the observation group,the range of motion of flexion,extension,left flexion,right flexion,left rotation and right rotation increased more significantly in the treatment group(P＜0.05).Conclusion Meridian massage is effective in the treatment of cervical Spondylotic radiculopathy,which can effectively relieve neck pain,improve clinical symptoms and improve patient satisfaction.

Objective To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH).Methods Between July 2020 and April 2023,82 patients with lumbar disc herniation were selected,including 58 males and 24 females,aged from 23 to 55 years old with an average of(43.76±6.64)years old.According to the different treatment methods,they were divided into observation group and control group with 41 cases in each group.The control group was treated with routine treatment,and the observation group was treated with meridian massage on the basis of routine treatment.In the control group,there were 30 males and 11 females;aged from 22 to 52 years old with an average of(42.27±9.34)years old;the Body mass index(BMI)ranged from 19 to 28 kg·m-2 with an average of(23.82±1.08)kg·m-2;the course of disease ranged from 0.5 to 3.0 years(2.40±0.48)years.There were 28 cases in L4,5 segment and 13 cases in L5S1 segment.In the observation group,there were 28 males and 13 females;the age ranged from 19 to 54 years old(42.19±9.26)years old;the BMI ranged from 18 to 29 kg·m-2 with an average of(23.73±1.15)kg·m-2;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45)years;there were 26 cases in L4,5 segment and 15 cases in L5S1 segment.Visual analogue scale(VAS),Oswestry disability index(ODI),M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment,and the clinical efficacy was evaluated by the standard of curative effect evaluation.Results After treatment,VAS[(3.24±1.45)vs(4.46±0.64)],ODI[(11.45±1.98)％vs(17.21±2.74)％]and TCM symptom score[(2.03±0.27)vs(3.99±0.54)]of the observation group were lower than those of the control group.The score of M-JOA[(23.43±2.61)vs(19.37±1.62)]increased(P＜0.05).The scores of VAS,ODI andTCM symptoms in the observation group were lower than those in the control group,while the scores of M-JOA were higher than those in the control group(P＜0.05).Conclusion Meridian massage is effective in the treatment of LDH,which can effectivelyrelieve low back pain,improve clinical symptoms and increaselumbar function,which is worthy of clinical promotion.

ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.

Objective:This study aims to explore the synergistic effects of DIP and other medical insurance supply-side policies.Method:City A that has piloted DIP reform was set as the treatment group,and City B without reform was set as the control group.A total of 1 120 public medical institution samples from 2019 to 2022 were collected.The total medical expenses during hospitalization and some structural expenses were analyzed using DID method.Result:DIP had a significant inhibitory effect on the medical expenses,and the expenses of checkups and examinations during hospitalization in city A,but had no impact on the drug and the material expenses during hospitalization.Conclusion:DIP played a significant cost control role and effectively controlled the total medical expenses during hospitalization.The synergistic effects of price adjustment of medical services policy and national centralized drug/material procurement policy on cost control were insufficient.DIP synergized with other supply-side policies to promote rational medical cost structure.It is suggested that medical insurance departments should focus on the synergistic effects of medical insurance supply-side policies to jointly improve the efficiency of medical insurance fund utilization.

Glomerular filtration rate(GFR)is a critical indicator of renal function assessment,which exhibits age-dependency in children and may differ from adults under various disease conditions.In recent years,there has been a growing focus on GFR among scholars,with an increasing number of clinical studies dedicated to refining and optimizing GFR estimation to span all pediatric age groups.However,the methods and assessment equations for estimating GFR may vary under different disease conditions,affecting the accuracy and applicability of assessments.This article reviews the peculiarities of renal function in children,explores GFR measurement methods,and evaluates the application of various GFR assessment equations in pediatric clinical practice,providing a reference for clinical assessment of renal function in children.

Objective To integrate tumor proliferation and immune-related biomarkers to construct a nomogram prediction model for predicting the prognosis of ovarian cancer patients.Methods We collected clinical information from patients diagnosed with epithelial ovarian cancer(EOC)between 2009 and 2013.Immunohistochemical staining was performed to detect the expression levels of KI67,epidermal growth factor receptor(EGFR)and programmed death-ligand 1(PD-Ll)in tumor tissues.We employed Lasso-Cox regression to identify variables and construct the nomogram model.We used time-dependent receiver operating characteristic(ROC)curves,concordance index,calibration curves,and decision curve analysis(DC A)curves to assess the model's discrimination,calibration,and net clinical benefit ability,respectively.Additionally,we conducted Kaplan-Meier survival analysis to assess the prognostic value of the model's risk score.Results We included a total of 131 EOC patients who were randomly assigned to the training set(n=79)and validation set(n=52)in a 6∶4 ratio.Lasso-Cox regression identified seven variables for constructing the nomogram prediction model.The AUCs for 1-,4-,and 6-year overall survival in the training set were 0.911,0.943,and 0.968,respectively,with a consistency index of 0.86[95％confidence interval(CI):0.81-0.91].In the validation set,the AUCs for 1-,4-,and 6-year overall survival were 0.830,0.797,and 0.828,respectively,with a consistency index of 0.71(95％CI:0.64-0.78).The calibration curves in both training and validation sets demonstrated strong agreement between model-predicted survival and actual outcomes(all P＞0.05).DCA curves indicated that the modeled net clinical benefit outperformed TNM staging.Patients with high-risk scores in the model exhibit poorer overall survival(P＜0.01)and progression-free survival(P＜0.01).Conclusion The successful development and validation of a nomogram prediction model based on tumor proliferation and immune-related biomarkers offer an efficient and straightforward clinical tool.This tool holds promise for enabling personalized treatment strategies for patients with ovarian cancer.

Objective:To explore the expressions of zinc homeostasis-related proteins,G protein-coupled receptor 39(GPR39)and ANO1 mRNA in the sperm of patients with asthenozoospermia(AS),and analyze their correlation with sperm motility.Methods:We collected semen samples from 82 male subjects with PR+NP＜40％,PR＜32％and sperm concentration＞15 × 106/ml(the AS group,n=40)or PR+NP≥40％,PR≥32％and sperm concentration＞15 × 106/ml(the normal control group,n=42).We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system,detected the expressions of zinc transporters(ZIP13,ZIP8 and ZNT10),metallothioneins(MT1G,MT1 and MTF),GPR39,and calcium-dependent chloride channel protein(ANO1)in the sperm by real-time quantitative PCR(RT qPCR),examined free zinc distribution in the sperm by laser confocal microscopy,and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining,followed by Spearman rank correlation analysis of their correlation with semen parameters.Results:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups(P＞0.05).Compared with the controls,the AS patients showed a significantly reduced free zinc level(P＜0.05),relative expressions of MT1G,MTF,ZIP13,GPR39 and ANO1 mRNA(P＜0.05),and that of the GPR39 protein in the AS group(P＜0.05).No statistically significant differences were observed in the relative expression levels of ZIP8,ZNT10 and MT1 mRNA between the two groups(P＞0.05).The relative expression levels of GPR39,ANO1,MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm(P＜0.05).Conclusion:The expressions of zinc homeostasis proteins(MT1G,MTF and ZIP13),GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia pa-tients,and positively correlated with sperm motility.

The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg^-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg^-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC₅₀ = 16.94 μg·mL^-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL^-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.