OBJECTIVE To establish the graded management standards for off-label use of Shenqi fuzheng injection. METHODS Systematic searches were conducted in databases including CNKI， PubMed and the Cochrane Library to retrieve guidelines/consensuses， systematic reviews/meta-analyses， and randomized controlled trials （RCTs） of Shenqi fuzheng injection. The quality of evidence was evaluated using AGREE Ⅱ， AMSTAR Ⅱ， and the Risk of Bias 1.0 tool recommended by Cochrane Collaboration， and the graded management standard for off-label use of Shenqi fuzheng injection was developed by using the Thomson grading system. RESULTS A total of 534 articles were involved， including 11 guidelines， 22 systematic reviews/meta-analysis， and 501 RCTs. They covered 79 off-label indications for Shenqi fuzheng injection： cancer-related fatigue， colorectal cancer and breast cancer， all with high-quality evidence were classified under grade A management （grade Ⅰ commendation）， allowing all physicians across the hospital to prescribe relevant treatments； five diseases， such as ovarian cancer， liver cancer， leukemia， heart failure and cerebral infarction， were classified under grade B management （grade Ⅱa commendation）， with prescription restricted to physicians with intermediate or higher professional titles in specific departments； eleven diseases， including sepsis， cervical cancer， esophageal cancer， etc.， were classified under grade C management （grade Ⅱb commendation）， requiring strict evaluation by senior physicians before prescription； the use of Shenqi fuzheng injection for other conditions was explicitly prohibited due to a lack of sufficient evidence. CONCLUSIONS Off-label use of Shenqi fuzheng injection is prevalent. The graded management standard established by evidence-based medical approach provides a scientific basis for standardizing the clinical application of traditional Chinese medicine injections and offers an operable paradigm for implementing differentiated drug use supervision in medical institutions.

Objective:To utilize the left ventricular myocardial work（LVMW）technique for early identification of myocardial damage in patients with fabry disease（FD）.Methods:In an observational cross-sectional study，35 patients with FD who visited the Second Hospital of Hebei Medical University from February 2023 to April 2024 were included. They were categorized into two groups based on left ventricular mass index（LVMI）：the non-left ventricular hypertrophy group（LVH-FD group，14 cases）and the left ventricular hypertrophy group（LVH+FD group，21 cases）. Further gender-stratified analysis was performed on parameters related to left ventricular global longitudinal strain（LVGLS）and LVMW. Additionally，for the FD group with normal LVGLS，a comparison of their LVMW-related parameters was made with a control group. A control group consisting of 28 healthy subjects from the same period was selected for comparison. The LVGLS，global work index（LVGWI），global constructive work（LVGCW），global wasted work（LVGWW），and global work efficiency（LVGWE）of the three groups were analyzed using two-dimensional speckle tracking and non-invasive myocardial work techniques，and intergroup comparisons of these parameters were performed. Pearson's linear correlation was applied to analyse the correlation between LVGWI，LVGWE and LVMI.Results:① According to the LVMI grouping results，compared with the control group，the LVH-FD group showed decreased LVGWI（ P<0.05），while the LVH+FD group exhibited reductions in LVGLS，LVGWI，and LVGWE（all P<0.05）. Compared to the LVH-FD group，the LVH+FD group demonstrated lower LVGLS，LVGWI，and LVGWE（all P<0.05）. ② Gender subgroup analysis revealed that in the female subgroup，no statistically significant differences were observed in LVGLS，LVGWI，and LVGWE between the female control group and the female LVH-FD group（all P>0.05）. However，the female LVH+ FD group showed decreased LVGLS，LVGWI，and LVGWE compared to both the female control group（all P<0.05）and the female LVH-FD group（all P<0.05）. In the male subgroup，compared to the male control group，the male LVH-FD group had reduced LVGWI（ P<0.05）but no significant differences in LVGLS or LVGWE（both P>0.05）. The male LVH+ FD group displayed lower LVGLS，LVGWI，and LVGWE compared to both the male control group（all P<0.05）and the male LVH- FD group（all P<0.05）. ③Compared with the control group，the LVGLS-normal FD group had a reduced LVGWI（ P<0.05），while there were no statistically significant differences in LVGLS，LVGWE，LVGCW，and LVGWW between these two groups（all P>0.05）. ④LVGWI and LVGWE were negatively correlated with LVMI（ r=-0.617，-0.707；both P<0.001）. Conclusions:LVMW can detect early cardiac dysfunction in patients with FD and is of guiding value for their clinical management.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective:To utilize the left ventricular myocardial work（LVMW）technique for early identification of myocardial damage in patients with fabry disease（FD）.Methods:In an observational cross-sectional study，35 patients with FD who visited the Second Hospital of Hebei Medical University from February 2023 to April 2024 were included. They were categorized into two groups based on left ventricular mass index（LVMI）：the non-left ventricular hypertrophy group（LVH-FD group，14 cases）and the left ventricular hypertrophy group（LVH+FD group，21 cases）. Further gender-stratified analysis was performed on parameters related to left ventricular global longitudinal strain（LVGLS）and LVMW. Additionally，for the FD group with normal LVGLS，a comparison of their LVMW-related parameters was made with a control group. A control group consisting of 28 healthy subjects from the same period was selected for comparison. The LVGLS，global work index（LVGWI），global constructive work（LVGCW），global wasted work（LVGWW），and global work efficiency（LVGWE）of the three groups were analyzed using two-dimensional speckle tracking and non-invasive myocardial work techniques，and intergroup comparisons of these parameters were performed. Pearson's linear correlation was applied to analyse the correlation between LVGWI，LVGWE and LVMI.Results:① According to the LVMI grouping results，compared with the control group，the LVH-FD group showed decreased LVGWI（ P<0.05），while the LVH+FD group exhibited reductions in LVGLS，LVGWI，and LVGWE（all P<0.05）. Compared to the LVH-FD group，the LVH+FD group demonstrated lower LVGLS，LVGWI，and LVGWE（all P<0.05）. ② Gender subgroup analysis revealed that in the female subgroup，no statistically significant differences were observed in LVGLS，LVGWI，and LVGWE between the female control group and the female LVH-FD group（all P>0.05）. However，the female LVH+ FD group showed decreased LVGLS，LVGWI，and LVGWE compared to both the female control group（all P<0.05）and the female LVH-FD group（all P<0.05）. In the male subgroup，compared to the male control group，the male LVH-FD group had reduced LVGWI（ P<0.05）but no significant differences in LVGLS or LVGWE（both P>0.05）. The male LVH+ FD group displayed lower LVGLS，LVGWI，and LVGWE compared to both the male control group（all P<0.05）and the male LVH- FD group（all P<0.05）. ③Compared with the control group，the LVGLS-normal FD group had a reduced LVGWI（ P<0.05），while there were no statistically significant differences in LVGLS，LVGWE，LVGCW，and LVGWW between these two groups（all P>0.05）. ④LVGWI and LVGWE were negatively correlated with LVMI（ r=-0.617，-0.707；both P<0.001）. Conclusions:LVMW can detect early cardiac dysfunction in patients with FD and is of guiding value for their clinical management.

Objective:To evaluate the degree of left atrial fibrosis in patients with persistent atrial fibrillation(AF) using four-dimensional automic left atrial quantitation(4D Auto LAQ).Methods:A total of 60 patients with persistent AF who underwent transcatheter radiofrequency ablation in the Second Hospital of Hebei Medical University from March 2022 to March 2023 were included. Patients were grouped according to the low-voltage area (mild<5%, moderate 5%-20%, severe>20%). General clinical data, conventional echocardiogram parameters, left atrial strain and related parameters of each group were compared. The relevant factors were obtained by Logistic regression analysis. The factor with the highest accuracy and its cut-off value was obtained by the ROC curve.Results:Sixty patients with persistent atrial fibrillation, were divided into mild low-voltage group(22 cases), moderate low-voltage group(20 cases), and severe low-voltage group(18 cases). There were statistical differences in gender, CHA2DS2-VASc score, peak value of early diastolic velocity of mitral inflow/average peak value of early diastolic tissue Doppler velocity of mitral annulus (E/e′), left atrial diameter (LAD), left atrial volume index (LAVI), left atrial maximal volume (LAVmax), left atrial minimal volume (LAVmin), left atrial total emptying fraction (LAEF), left atrial reservoir longitudinal strain (LASr), left atrial reservoir circumferential strain (LASr-c), left atrial myocardial work (LA MW, LA MW-c), left atrial stiffness (LA stiffness, LA stiffness-c) among the 3 groups(all P<0.05). The LASr had the highest correlation with low voltage area ( rs=-0.814, P<0.001). Logistic regression analysis showed that CHA2DS2-VASc, LAD, LAVI, LAVmax, LAVmin, LAEF, LASr, LASr-C, LA MW, LA MW-C, LA stiffness and LA stiffness-c could all predict the low voltage area(all P<0.05). The LA stiffness had the highest AUC (0.952). The cut-off value of severe low voltage was 1.15, the sensitivity was 94.4%, and the specificity was 83.3%. Conclusions:4D Auto LAQ can be used to evaluate the degree of left atrial fibrosis. The correlation between LA stiffness and substrate voltage mapping is the highest.

ObjectiveTo investigate the late diagnosis of HIV infection and associated factors in Jiading District between 1998 and 2022， and to provide the information for the development of AIDS prevention and control strategy. MethodsInformation of newly reported HIV/AIDS cases in Jiading District between 1998 and 2022 were obtained from the National Information System for Comprehensive AIDS Prevention and Control. Logistic regression was used to explore the associated factors of late diagnosis of HIV infection. ResultsIn total， 809 HIV/AIDS cases was newly reported， 324 of which were late diagnosis with the overall rate of late diagnosis of 40.1%. Despite an increased tendency from 2016 to 2018， the rate of late diagnosis showed a downward trend from 1998 to 2015. The late diagnosis rate was 29.5% in 2015. From 2016 to 2022， the average rate was 34.9%. The average age of cases with a late diagnosis was 44.8±14.6 years old. Age groups over 50 had the highest risk，at 57.7%， accounting for 35.8% of all cases of late diagnosis. All age groups older than 30（OR=1.37‒3.50） had a higher rate of late diagnosis than the group between age 21 and 30. In comparison to patients at VCT clinic， the rate of late diagnosis among sexually transmitted disease （STD） outpatients （OR=2.23， 95%CI：1.42‒3.49） and other clinical patients （OR=2.75， 95%CI：1.88‒4.01） was higher. ConclusionThe late diagnosis rate of HIV infection is relatively high in Jiading District. AIDS education and prevention activities should be strengthened among people aged over 50 years. For early detection of HIV infection， VCT clinic platform’s function should be fully utilized. Medical institutions should pay attention to HIV testing in patients.

Objective:To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis (LM) from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.Methods:A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital, Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected, and divided into 30, 40 and 50 mg groups ( n=10, n=4, n=7) according to pemetrexed dose. Cerebrospinal fluid was collected at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy, and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid, to clarify the drug-related pharmacokinetic parameters, and to compare the differences in pemetrexed concentration among groups. Finally, cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results:There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy (30 mg group: F=20.56, P<0.001; 40 mg group: F=27.06, P<0.001; 50 mg group: F=28.63, P<0.001), and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5, 1, 2, 4, 6 and 12 h compared to 0 h after intrathecal injection chemotherapy (all P<0.05). Compared to the 30 mg group, cerebrospinal fluid drug concentrations in the 50 mg group increased at 1, 2, 4, 6, 12 and 24 h after intrathecal injection chemotherapy, with statistically significant differences (all P<0.05). Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve (AUC) 0-∞ of the 30, 40 and 50 mg groups were (5 696.12±283.32), (7 886.29±396.57), and (14 202.70±440.19) h·mg/L, respectively, with a statistically significant difference ( F=1 159.00, P<0.001) ; AUC 0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; AUC 0-∞ increased in the 40 mg group compared to the 30 mg group ( P<0.05). The half-lives of three groups were (8.75±0.23), (11.29±0.59) and (16.42±1.23) h, respectively, with a statistically significant difference ( F=206.80, P<0.001) ; half-life was longer in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; half-life was longer in the 40 mg group compared to the 30 mg group ( P<0.05). The peak time of three groups were (1.55±0.10), (1.00±0.01), (1.43±0.11) h, respectively, with a statistically significant difference ( F=48.11, P<0.001) ; the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group (both P<0.05). Clearance of three groups were (7.02±2.46), (5.80±1.25) and (3.66±1.32) L/h, respectively, with a statistically significant difference ( F=6.02, P=0.009) ; clearance was decreased in the 50 mg group compared to the 30 mg group ( P<0.05). The peak concentration of three groups were (540.45±32.25), (820.75±46.47) and (1 014.78±64.96) mg/L, respectively, with a statistically significant difference ( F=207.70, P<0.001) ; peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; peak concentration increased in the 40 mg group compared to the 30 mg group ( P<0.05). Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy, in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were (13.76±4.79), (11.41±7.08), (9.41±2.59) and (7.86±4.02) mg/L, respectively; 40 mg group were (14.45±6.59), (12.87±15.73), (11.24±2.48) and (9.09±3.38) mg/L, respectively; 50 mg group were (12.94±10.34), (9.72±7.62), (8.15±8.17) and (4.34±4.21) mg/L, respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group ( F=4.04, P=0.016), and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 (both P<0.05). There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups ( F=0.28, P=0.837; F=3.57, P=0.066) . Conclusion:Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid; dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Background Occupational stress and depressive symptoms of disease prevention and control personnel are serious. Objective To investigate the relationship between occupational stress, psychological capital, and depressive symptoms of disease prevention and control personnel, and analyze the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms. Methods From July to September 2020, a cluster random sampling method was used to select 2201 employees from 21 centers for disease control and prevention as study subjects covering all levels of administrative divisions in Jiangsu Province. A total of 2036 valid questionnaires were collected with a recovery rate of 92.5%. The Core Occupational Stress Scale, Patient Health Questionnaire, and Psychological Capital Questionnaire were used to investigate their occupational stress, depressive symptoms, and psychological capital. Stratified regression analysis was used to explore the effects of occupational stress and psychological capital on depressive symptoms. A mediating effect model was used to analyze and verify the potential mediating effect of psychological capital on the relationship between occupational stress and depressive symptoms. Results The total scores in M (P₂₅, P₇₅) of occupational stress, depressive symptoms, and psychological capital in the target population were 42.0 (37.0, 48.0), 8.0 (4.0, 9.0), and 4.6 (4.0, 5.0) respectively. The positive rate of occupational stress was 31.0% (631/2036), and the positive rate of depressive symptoms was 22.0% (448/2036). The dimensional scores of organization and reward, and demand and effort of occupational stress were positively correlated with the total score of depressive symptoms [Spearman correlation coefficients (r_s) were 0.371 and 0.269, P<0.05]. The dimensional scores of social support and autonomy of occupational stress and the score of psychological capital were negatively correlated with the total score of depressive symptoms (r_s=−0.373, −0.112, −0.494, P<0.05). The organization and reward, and demand and effort had positive effects on depressive symptoms (b=0.188, 0.177, P<0.05), while social support and autonomy had negative effects on depressive symptoms (b=−0.290, −0.078, P<0.05), and associated with a 22.5% increase of explanatory variance. Psychological capital had a negative effect on depressive symptoms (b=−0.368, P<0.05), and associated with an 11.0% increase of explanatory variance. Psychological capital had mediating effects on the associations of social support, organization and reward, and autonomy with depressive symptoms, and the mediating effect values were −0.210 (95%CI: −0.253-−0.171), 0.096 (95%CI: 0.071-0.122), and −0.164 (95%CI: −0.229-−0.103), respectively. The corresponding mediating effect percentages were 40.23%, 26.97%, and 45.56%, respectively. Conclusion Occupational stress of disease prevention and control personnel can directly affect depressive symptoms, but also indirectly through psychological capital. Psychological capital plays a partial mediating role in the associations of social support, organization and reward, and autonomy of occupational stress with depressive symptoms. The occurrence of depressive symptoms can be reduced by decreasing occupational stress and increasing psychological capital.

ObjectiveTo explore the diagnoses of diseases and functioning of speech fluency disorder, analyze the main assessment content, and construct framework of intervention solution based on International Classification of Diseases 11th Revision (ICD-11), International Classification of Functioning, Disability and Health (ICF) and International Classification of Health Interventions (ICHIβ-3). MethodsThe diagnoses of diseases and functioning was discussed with ICD-11 and ICF. The assessment tools were analyzed with ICF. A holistic intervention solution was constructed with ICF and ICHIβ-3. ResultsSpeech fluency disorder is classified as 6A01.1 developmental speech fluency disorder for ICD-11. The related diseases include 6A01.0 developmental speech sound disorder, 6A01.2 developmental language disorder, cerebral palsy, MA80.0 aphasia, MA80.1 dysphasia and MA80.2 dysarthria, etc. For ICF, the categories related to speech fluency disorder might be s3 structures invovled in voice and speech; b3 voice and speech functions, especially b330 fluency and rhythm of speech functions; d1 learning and applying knowledge, d3 communication, especially d330 speaking and d355 discussion, d7 interpersonal interactions and relationships, and d9 community, social and civic life. A holistic intervention solution for speech fluency disorder was developed, involving in body structure, body function, activities and participation, and environmental factors, including assessment, training and treatment, educational counseling, and psychological and social support, etc. ConclusionA framework of diagnosis, assessment and rehabilitation has been constructed for speech fluency disorder.