Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

Objective:To investigate the clinical value of ultrasound-guided thoracic paravertebral block (TPVB) combined with bronchial blocker (BB) placement in thoracoscopic surgery.Methods:A randomized controlled study was conducted involving 60 patients scheduled for thoracoscopic surgery at The First Affiliated Hospital of Xiamen University from November to December 2023. These patients were classified as American Society of Anesthesiologists (ASA) I-II. They were divided into an observation group (BB placement) and a control group (double-lumen bronchial blocker placement) using the random number table method, with 30 patients in each group. Preoperatively, TPVB was performed under ultrasound guidance. After the induction of general anesthesia, a single-lumen tracheal tube was inserted, followed by the placement of a BB in the observation group, while a corresponding type of double-lumen bronchial tube was inserted in the control group. A fiberoptic bronchoscope was used for positioning and fixation in both groups, and anesthesia was maintained with intravenous anesthesia. The following parameters were assessed in each group: positioning time for intubation; number of cases with tube displacement; number of cases of postoperative pharyngeal pain; hemodynamic parameters [mean arterial pressure (MAP) and heart rate (HR)] before and after intubation; and blood gas analysis [partial pressure of oxygen (PaO 2) and carbon dioxide (PaCO 2)]. Additionally, the surgical field exposure score and the dosages of propofol and remifentanil administered during surgery were recorded. Levels of inflammatory markers [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, and TNF-β] and Visual Analog Scale scores for pain at rest and during cough, recorded at 2, 4, 8, 10, 12, and 24 hours postoperatively were compared between the two groups. Results:The total amounts of propofol [(569.7 ± 29.2) mg] and remifentanil [(289.3 ± 46.3) μg] in the observation group were significantly lower than those in the control group [(612.6 ± 28.7) mg, (361.7 ± 40.6) μg, t = 5.74, 6.44, both P = 0.001]. The recovery time in the observation group [(31.8 ± 11.4) minutes] was significantly shorter than that in the control group [(37.5 ± 10.1) minutes, t = 2.10, P = 0.040]. There was no significant difference in positioning time for intubation between observation and control groups [(67 ± 13) seconds vs. (80 ± 36) seconds, t = 1.86, P = 0.068). There was no significant difference in percentage of cases who underwent tube displacement after intubation between observation and control group [23.3% (7/30) vs. 16.7% (5/30), χ2 = 0.58, P = 0.445]. The incidence of postoperative pharyngeal pain in the observation group was significantly lower than that in the control group [10.0% (3/30) vs. 33.3% (10/30), χ2 = 5.02, P = 0.025). There were no statistically significant differences between the two groups in terms of number of cases with tube displacement, hemodynamic parameters, blood gas analysis, inflammatory markers, surgical field exposure, and postoperative Visual Analog Scale scores between the two groups (all P > 0.05). Conclusion:Ultrasound-guided TPVB combined with BB placement during thoracoscopic surgery can reduce airway injury compared with the use of a double-lumen bronchial tube. It provides adequate sedation and analgesia during the procedure, facilitates rapid awakening, promotes early recovery of spontaneous breathing, and has fewer adverse reactions, making it worthy of clinical promotion.

Objective To investigate the effect of electroencephalography(EEG)phase synchronization on upper limb function in post-stroke aphasia patients.Methods A total of 33 stroke patients admitted to Neurological Rehabilitation Center,Yangzhi Rehabilitation Hospital affiliated to Tongji University from October 2020 to June 2023 were retrospectively included.The general data of the patients were collected,including gender,age,course of disease(onset to enrollment time),type of stroke(cerebral hemorrhage,cerebral infarction)and function scores of hemiplegic upper limbs.All patients underwent the Boston diagnostic aphasia test(BDAE)within 1 week after admission,and the aphasia quotient(AQ)test was performed for those with BADE＜5,and the AQ＜93.8 score was defined as aphasia.AQ ≥ 93.8 score was non-aphasia,and the hemiplegic upper limb function was evaluated by using the function test for the hemiplegic upper extremity-Hong Kong Version(FTHUE-HK)classification(FTHUE-HK1-7 grades were assigned as 1-7 points,respectively),and the EEG data of all patients were collected.The EEG phase synchronization index(PSI)of 5 frequency bands(δ,θ,α,β,and y)in the language-motor regions(C3F7,C3T5),motor-sensory regions(C3P3)and motor regions(C3C4)were calculated and compared between groups.Spearman's correlation was used to analyze the correlation between PSI and FTHUE-HK scores in post-stroke aphasia group.Results A total of 33 patients were included in this study.There were 1 7 patients in the post-stroke aphasia group,including 11 males and 6 females,age range 50-75 years,mean ages(63±12)years and an average AQ of(22.5±18.2)score.There were 16 patients in the non-aphasia group after stroke,including 12 males and 4 females,age range 47-74 years,mean age(58±11)years and an average AQ of(99.1±0.3)score.(1)There were no significant differences in gender,age,course of disease,and stroke type between the two groups(all P＞0.05).The FTHUE-HK score in the post-stroke aphasia group was lower than that in the non-aphasia group([1.6±1.1]score vs.[3.0±1.2]score),and the difference between two groups was statistically significant(P=0.003).(2)The C3F7-PSI in the post-stroke aphasia group was higher in the δ and θ frequency bands than those in the non-aphasia group(δ:t=3.869,P=0.001;θ:t=3.409,P=0.002);the C3T5-PSI in the post-stroke aphasia group was higher than those in the θ and δ bands(θ:t=2.376,P=0.024;δ:t=2.787,P=0.009).The C3P3-PSI in the post-stroke aphasia group was higher in the δ and θ bands than those in the non-aphasia group(δ:t=2.761,P=0.010;θ:t=2.834,P=0.008);the C3C4-PSI in the post-stroke aphasia group was significantly higher in the α,θ,and δ bands than those in the non-aphasia group,and the differences between two groups were statistically significant(α:t=2.426,P=0.021;θ:t=3.263,P=0.003;δ:t=2.851,P=0.008).(3)The C3F7-PSI was moderately negative correlated with FTHUE-HK scores in the δ and θ bands of patients in the post-stroke aphasia group(δ:r=-0.540,P=0.041;θ:r=-0.425,P=0.035).The C3P3-PSI in the post-stroke aphasia group was positively correlated with the FTHUE-HK scores in the γ band(r=0.519,P=0.033).In the post-stroke aphasia group,C3C4-PSI was negatively correlated with FTHUE-HK scores in the δ band(r=-0.510,P=0.036).The FTHUE-HK score was not correlated with the PSI of frequency bands in the remaining language-motor regions,motor-sensory regions and motor regions(all P＞0.05).Conclusions Patients with post-stroke aphasia have worse upper limb dysfunction than those without post-stroke aphasia.The EEG phase synchronicity of left frontoparietal lobe δ and θ of patients with post-stroke aphasia was higher than those of patients without post-stroke aphasia and correlated with the FTHUE-HK score of upper limb function.The results need to be further verified.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

Objective This paper analyzed the characteristics and changes in the disease spectrum of internal medicine inpatients of a tertiary hospital in Zhongshan City.It aimed to explore the evolving trends in disease ranking and treatment charac-teristics to provide a scientific basis for enhancing hospital management.Methods This paper selected 26 053 patients dis-charged from the internal medicine department of the tertiary hospital in Zhongshan City between January 1,2018,and December 31,2022.A retrospective analysis was used to classify these patients by ages,hospitalization date,and relative weight.Results In the past five years,those discharged patients showed no significant increase in the number,but a significant increase in age and ase Mix Index(CMI).Conclusion Since the outbreak of COVID-19,intractable inpatients in the hospital has steadily in-creased in number each year,while the diseases spectrum remains stable.The CMI of circulatory system,respiratory system,and nervous system diseases is relatively high.As key tricky components of internal medicine,these sub-specialties should concentrate on enhancing diagnostic and treatment capabilities as well as service quality to offer improved healthcare services to the public.

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).