BACKGROUND:Adolescent lumbar disc herniation is the main cause of low back pain in adolescents. At present,most of them are treated by conservativetreatment. When long-term non-surgical treatment attempts,surgery may be necessary to prevent further injury when the patient's symptoms are notsufficiently relieved or when the patient has symptoms of single nerve paralysis or compression of the cauda equina,it is very important to choose a suitable interbody fusion device for the surgical treatment of the patients.OBJECTIVE:To explore the effects of minimally invasive interbody fusion with different heights on lumbar biomechanics in patients with adolescent lumbar disc herniation.METHODS:CT scans of a 17-year-old male patient with adolescent lumbar disc herniation (L4-5 segment herniation) were collected. After the three-dimensional reconstruction of MIMICS,the interbody fusion device equal to and 3 mm higher than the intervertebral space was selected for analysis,so two expandablemixed material interbody fusion devices were designed and reconstructed. Fusion device L:11 mm high front,9 mm high posterior,9 mm wide,28 mmlong,and fusion device H:14 mm high front,11 mm high posterior,11 mm wide,28 mm long and the lumbar fusion device was modeled. The fusion deviceand lumbar spine model were optimized,inversely modeled,and then imported into ABAQUS,and finally the 3D model of lumbar fusion was obtained.The physiological activities of the human body were simulated,such as lumbar extension,forward bending,right bending,and left bending,to obtain thecorresponding stress contours. The biomechanical characteristics of the L4-5 vertebra under seven different working conditions were observed.RESULTS AND CONCLUSION:(1) The maximum stress of the two kinds of fuses was in the condition of forward bending and backward extension,the stress value of H fuses was (18.27±3.80) Mpa and (15.02±3.24) Mpa;the stress value of L fuses was (9.16±0.05) Mpa and (9.17±1.83) Mpa. The stress values of the end plate of the H-fusion in the extension station were (19.11±4.03) Mpa and (16.32±3.72) Mpa respectively. The stress values of the L-fusion end plate were (9.13±0.01) Mpa and (4.92±1.01) Mpa respectively. (2) The stress of H-type fusing end plate was higher than that of L-type fusing end plate except for L-5 end plate at neutral position (P<0.05). (3) Choosing an interbody fusion device with a height of more than 3 mm in the same intervertebral space has a more stable biomechanics.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

Objective To investigate the effect of polymyxin B(PMB)combined with tigecycline(TGC)on delaying Klebsiella pneumoniae(KP)resistance to PMB,and to analyze the possible mechanisms involved in the induction and delay of resistance.Methods Six clinical isolates of KP strains from the Intensive Care Unit of First Affiliated Hospital of Army Medical University were subjected and then induced with PMB at 1/2 minimal inhibitory concentration(MIC)alone or combined with TGC at 1/2 and 1/4 MIC,respectively.The MIC changes of PMB in these strains were monitored over 14 consecutive passages.The strain 686K,which showed the most significant delay in resistance,was selected for further analysis.Differences in gene and protein expression were examined among the wild-type strain 686K,PMB-induced resistant strain(686K·R),and PMB combined with TGC delayed resistant strain(686K·DR)using transcriptome sequencing,qRT-PCR,and proteomics.Relevant target genes during the delay of resistance were analyzed through literature and bioinformatics analyses.Additionally,cpxR gene knockout strain 686K/ΔcpxR∷Apr and its complementation strain 686K/ΔcpxR∷Apr/pRK415-cpxR were constructed using homologous recombination technology to assess the expression levels of resistance-related genes and changes in MIC after induction in vitro.Results Under sub-MIC(1/2)PMB alone,resistance developed in all 6 KP strains within 2 d,while,the combination with TGC significantly delayed the development of resistance.Transcriptomic and proteomic analyses indicated that in strain 686K·R,the expression levels of the PhoP/Q two-component system,lipopolysaccharide(LPS)modification enzymes,and efflux pump systems were significantly up-regulated(|Log2FC|≥2,P<0.0001),while TGC co-administration markedly inhibited these expression changes.The cpxR deletion and complementation strains were successfully constructed.The expression levels of resistance-related genes phoP,pmrD,and acrA were decreased in the cpxR deletion strain(P<0.001),and the resistance was delayed until day 6 under PMB monotherapy,whereas the complementation strain restored the resistance phenotype by day 2.In the absence of cpxR,the effect of PMB when combined with TGC on delaying resistance did not differ from that observed with PMB monotherapy.Conclusion The combination of PMB and TGC can delay KP resistance to PMB.cpxR,as a critical regulatory factor,can impact PMB resistance by modulating LPS modifications and the expression of the AcrAB-TolC efflux pump,and plays an important regulatory role in the process of resistance induction.

Objective To observe the value of T2 mapping for quantitatively evaluating the changes of junctional zone and outer myometrium caused by endometrial fibrosis.Methods A total of 73 infertility patients with endometrial fibrosis confirmed by hysteroscopy(disease group)and 33 healthy women of childbearing age(control group)were prospectively enrolled,and MR examinations were performed at the late proliferative phase of endometrium.The thickness and T2 value of junctional zone,T2 value of outer myometrium on anterior,posterior and fundus wall of midsagittal corpus uteri were measured,and the mean value of the above measurements on the three walls were calculated.Receiver operating characteristic curves were constructed,the areas under the curves(AUC)were calculated to explore the efficacy of those with significant difference among the mean thickness and the mean T2 value of junctional zone,the mean T2 value of outer myometrium and their combination for evaluating endometrial fibrosis.Results The thickness and T2 value of anterior wall,posterior wall,fundus wall and the mean junctional zone in disease group were all significantly higher than those in control group(all P＜0.001).No significant difference of T2 value of anterior wall,posterior wall,fundus wall nor the mean outer myometrium was found between groups(all P＞0.05).The mean thickness and the mean T2 value of junctional zone and their combination could be used to effectively evaluate endometrial fibrosis,with AUC of 0.839,0.822 and 0.922,respectively,and their combination had the best performance(both P＜0.01).Conclusion T2 mapping could be used to quantitatively evaluate the injury of junctional zone caused by endometrial fibrosis.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective:To compare the surface electromyography characteristics of essential tremor (ET), Parkinson′s disease (PD) and essential tremor-Parkinson′s disease syndrome (ET-PD).Methods:A total of 74 patients [ET group ( n=23), PD group ( n=30), and ET-PD group ( n=21)] admitted to the Parkinson′s and Movement Disorders Center of the Department of Neurology of Xuanwu Hospital from August 2020 to December 2023 were enrolled, and results of their bilateral upper limbs surface electromyography (sEMG) were collected. sEMG activities were analyzed offline. Power spectral analysis was performed to explore the sEMG activities. One-way analysis of variance and chi-square test were used to compare the differences of electrophysiological parameters. Results:For the ET group characterized by postural tremor, the frequency was (6.06±0.68) Hz, the amplitude was (1 200.91±360.69) μV, the proportion of alternating contractions was 30.4% (7/23), and the proportion of harmonic resonances was 34.8% (8/23). For the PD group characterized by rest tremor, the frequency was (4.81±0.61) Hz, the amplitude was (1 057.40±354.52) μV, the proportion of alternating contractions was 73.3% (22/30), and the proportion of harmonic resonances was 70.0% (21/30). For the ET-PD group in rest and postural state respectively, the frequencies were (5.04±0.44) Hz and (5.80±0.47) Hz, the amplitudes were (1 026.05±191.90) μV and (1 196.67±212.12) μV, the proportions of alternating contractions were 52.4% (11/21) and 38.1% (8/21), and the proportions of harmonic resonances were 52.4% (11/21) and 33.3% (7/21). Analysis of variance revealed that tremor frequencies for the PD group and the ET-PD group in rest state were lower than the ET group and the ET-PD group in postural state ( F=27.439, P<0.001). The proportion of alternating contractions for the PD group was higher than the ET group ( χ 2=9.669, P=0.002) and the ET-PD group in postural state ( χ 2=6.333, P=0.012). The proportion of harmonic resonances for the PD group was higher than the ET group ( χ 2=6.517, P=0.011) and the ET-PD group in postural state ( χ 2=6.708, P=0.010). No statistically significant differences were found for tremor amplitudes among all the groups ( F=2.143, P=0.100). Conclusions:ET is characterized by postural tremors, with a higher frequency and a lower alternating contractions and harmonic resonances. PD is characterized by rest tremors, with a lower frequency and a higher alternating contractions and harmonic resonances. The parameters of ET-PD are between ET and PD, which provide objective evidences for differential diagnosis of tremors.

Objective:To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy related to the EEF1A2 gene. Methods:The clinical data and whole exome sequencing results of 2 patients who were diagnosed as developmental and epileptic encephalopathy related to the EEF1A2 gene in the Children′s Hospital, Capital Institute of Pediatrics in June 2016 and August 2018 were retrospectively analyzed. Relevant literatures were retrieved using " EEF1A2" and "epileptic encephalopathy" or "epilepsy" as key words in Online Mendelian Inheritance in Man, PubMed, CNKI and Wanfang databases (literatures searching from establishment of these databases to June 2024). The clinical and genetic characteristics of developmental and epileptic encephalopathy related to the EEF1A2 gene were summarized based on literature reports and the data of these 2 patients. Results:Patient 1 was a 9 months old male infant. He presented with global developmental delay. He developed myoclonic seizures at 4 months old. Valproic acid, clonazepam, topiramate and vagus nerve stimulation were all ineffective. Both of his hands had transverse palmar crease. The de novo c.364G>A variant in the EEF1A2 gene (NM_001958.3) was identified and he was diagnosed with developmental and epileptic encephalopathy related to the EEF1A2 gene. Patient 2 was a 2 years and 2 months old boy. He presented with global developmental delay. Myoclonic seizures occurred when he was 2 years and 3 months old, and various anti-epileptic drugs were ineffective. He had left eye esotropia and low muscle tone in the extremities. He died at the age of 4. The de novo c.208G>A variant in the EEF1A2 gene (NM_001958.3) was identified and he was diagnosed with developmental and epileptic encephalopathy related to the EEF1A2 gene. Eight literatures on developmental and epileptic encephalopathy related to the EEF1A2 gene (all in English) were retrieved, reporting 28 cases (totally 30 patients, including 2 cases in this study). The main clinical manifestations were psychomotor developmental delay (30/30, 100.0%), facial dysmorphism (15/30, 50.0%), refractory epilepsy (14/26, 53.8%), myoclonic seizures (19/26, 73.1%), and movement disorders (8/16). A total of 15 mutation sites in the EEF1A2 gene were reported, all of which were missense mutations. Conclusions:Developmental and epileptic encephalopathy related to the EEF1A2 gene is primarily characterized by delayed psychomotor development, distinctive facial features, drug-resistant epilepsy, myoclonic seizures, and movement disorders. Variants in the EEF1A2 gene are predominantly missense mutations, and identifying these variants plays a crucial role in accurate diagnosis of the disease.

Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.

Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.