OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system， optimization measures were taken， including improving the content of the rule base， adjusting the interception level and prompt mode， refining the working model of prescription review pharmacists， and strengthening clinical communication. A retrospective cohort study was conducted， with prescription data from June to December 2023 （before optimization） as the control group and June to December 2024 （after optimization） as the observation group. Through inter group comparative analysis， the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from （82.51± 4.04）% before optimization to （90.98±1.55）% after optimization； the false positive rate decreased from （20.87±1.64）% before optimization to （7.41±2.04）% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%， and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%， the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital， its prescription review efficiency has been significantly enhanced， the quality of prescriptions has steadily improved， and the accuracy of reviews has notably improved.

BACKGROUND: This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS: We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Humans ; Stomach Neoplasms/metabolism* ; Female ; Neoadjuvant Therapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use* ; Male ; Middle Aged ; Propensity Score ; Retrospective Studies ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Cohort Studies

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg^-1）， high-dose JTTP group （7.2 g·kg^-1）， and metformin group （0.2 g·kg^-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Middle-aged and elderly patients with femoral neck fracture often suffer from basic diseases. Conservative treatment will significantly increase the incidence of complications. At present, surgical treatment is mostly advocated. Internal fixation is one of the effective treatment methods for middle-aged and elderly patients with femoral neck fracture. It has the advantages of improving hip joint function, accelerating patient recovery, and improving patient quality of life. At present, there are many choices of internal fixation in the world, each has its own advantages and disadvantages, and there is no unified standard. Different surgical methods can be selected according to various factors such as fracture type, patient′s physical condition and surgical auxiliary technology. This article reviews the clinical progress of internal fixation for femoral neck fractures in middle-aged and elderly patients from four aspects: the characteristics of femoral neck fractures in middle-aged and elderly patients, common internal fixation methods, 3D printing guide plate auxiliary technology and artificial intelligence auxiliary technology.

ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

Serum cholinesterase(ChE)level is important for the diagnosis and prognostic evaluation of various diseases such as liver diseases and toxic diseases,and butyrylcholinesterase(BuChE)is an important component of ChE.Mutations in the BCHE gene can cause a significant reduction in the level of BuChE,with extensive reports in European and American populations and relatively few reports in Eastern countries,particularly China.This study describes a male patient,aged 35 years,who was misdiagnosed with organophosphorus pesticide poisoning due to an extreme reduction in ChE level and was given detoxification therapy,but such diagnosis was excluded by various biochemical examinations.Finally whole-exome sequencing and Sanger sequencing revealed the complex heterozygous mutations of c.1027dup and c.401dup at exon 2 of the BCHE gene,and hereditary BuChE deficiency due to these mutations is the cause of the extreme reduction in ChE level.

Objective To compare the changes of brain voxel-mirrored homotopic connectivity(VMHC)of patients before and after Tai Chi Chuan training based on functional magnetic resonance imaging(fMRI)technology;To discuss the central effect mechanism of Tai Chi Chuan in treating chronic fatigue syndrome(CFS).Methods A total of 25 CFS patients(experiment group)and 27 healthy individuals(control group)were recruited to undergo a 1-month Tai Chi Chuan intervention.All receive one month of Tai Chi Chuan training.Differences in SF-36 scores and VMHC between CFS patients and HCs were compared.Results Before training,the SF-36 scores in the experimental group were significantly lower than those in the control group(P<0.001),and the VMHC in the bilateral inferior occipital gyrus,paracentral lobule,lingual gyrus,insula and superior temporal gyrus brain areas were weakened.After training,the scores of SF-36 in the experimental group significantly increased(P<0.001),and the VMHC in bilateral inferior occipital gyrus,superior temporal gyrus,anterior cuneiform lobe and paracentral lobule were significantly enhanced.The difference in whole brain VMHC was positively correlated with the difference in energy scores in SF-36(r=0.456,P=0.025);some scores of SF-36 in the control group significantly increased(P<0.05),and no significant changes in VMHC were observed in brain regions.Conclusion Tai Chi Chuan can effectively improve the quality of life of patients with CFS.This change may be related to the enhancement of functional connections in brain regions such as inferior occipital gyrus,superior temporal gyrus,precuneus,paracentral lobule,et al.

Objective:To discuss the improvement effect of uric acid(UA)on the postoperative cognitive dysfunction(POCD)in the mice anesthetized with isoflurane for a long duration,and to clarify its possible mechanism.Methods:Twenty-four healthy male C57BL/6 mice were randomly divided into blank control group,anesthesia group,and UA group,and there were eight mice in each group.The mice in UA group were injected intraperitoneally with 200 μL UA solution daily for 2 d before anesthesia.The mice in blank control group and anesthesia group were given the same volume of saline;the mice in anesthesia group and UA group were used to prepare the models of long-duration isoflurane anesthesia,while the mice in blank control group were untreated.Y-maze tests was used to detect the alternation success rate,movement distances,and movement speeds of the mice in various groups;situational fear experiment was used to detect the percentages of freezing time;Western blotting method was used to detect the expression levels of interleukin(IL)-1β,IL-10,and mature brain-derived neurotrophic factor(mBDNF)proteins in hippocampus tissue of the mice in various groups.Results:The Y-maze test results showed that compared with blank control group,the alternation success rate of the mice in anesthesia group was significantly decreased(P<0.01);compared with anesthesia group,the alternation success rate of the mice in UA group was significantly increased(P<0.01).The situational fear experiment results showed that compared with blank control group,the percentage of freezing time of the mice in anesthesia group was significantly decreased(P<0.01);compared with anesthesia group,the percentage of freezing time of the mice in UA group was significantly increased(P<0.05).The cued memory experiment resutls showed that there were no significant differences of the percentage of freezing time of the mice between various groups(P>0.05).The Western blotting results showed that compared with blank control group,the expression level of IL-1β protein in hippocampus tissue of the mice in anesthesia group was increased(P<0.01),while the expression levels of IL-10 and mBDNF proteins were decreased(P<0.01);compared with anesthesia group,the expression level of IL-1β protein in hippocampus tissue of the mice in UA group was decreased(P<0.05),and the expression levels of IL-10 and mBDNF proteins were increased(P<0.05 or P<0.01).Conclusion:UA can improve the POCD in the mice,and its mechnasim may be related with its anti-inflammatory activity inhibiting the central inflammation and upregulating the mBDNF protein expression.

Alzheimer's disease (AD) is a central neurodegenerative disease with still unclear pathogenesis. Recent studies have shown that axonal transport dysfuction of mitochondria may contribute to AD progression. Normal mitochondrial axonal transport mainly involves microtubules, molecular motors and connexins, while AD early pathological changes can damage mitochondrial axonal transport by interfering with these proteins: accumulated β-amyloid (Aβ) impairs the function of molecular motors; abnormally modified Tau protein reduces microtubule stability; mutant presenilin-1 (PS1) can induce phosphorylation of some related proteins by activating glycogen synthase kinase-3β (GSK-3β); all these processes can damage mitochondrial axonal transport, leading to synaptic dysfunction. This review aims to clarify the possible mechanisms of axonal transport dysfuction of mitochondria in AD and provides new ideas for AD treatment.

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.
Arthrogryposis ; Child ; Facies ; Female ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Mutation