OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases. METHODS: Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated. RESULTS: Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3. CONCLUSION Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans ; Denosumab/therapeutic use* ; Bone Neoplasms/drug therapy* ; Prostatic Neoplasms/drug therapy* ; Male ; Randomized Controlled Trials as Topic ; Bone Density Conservation Agents/therapeutic use*

OBJECTIVE: To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods： The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well. RESULTS: AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP％, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP％, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility (［PR+NP］％), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05). CONCLUSION The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male ; Humans ; Autoantibodies ; Sperm Motility ; Semen ; Retrospective Studies ; Receptor, Angiotensin, Type 1/immunology* ; Animals ; Rats ; Angiotensin II ; Adult ; Sperm Count ; Semen Analysis ; Receptor, Angiotensin, Type 2/immunology*

OBJECTIVE: To explore the diagnostic value of shear wave elastography (SWE) for clinically significant prostate cancer (csPCa). METHODS: We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer (PCa) in Baoji Central Hospital from June 2017 to July 2023. All the patients underwent the following examinations in the order of serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS), measurement of the stiffness of the entire prostate gland by SWE, and TRUS-guided prostate puncture biopsy. The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base, middle, and apex of the prostate, including the maximum Young's modulus (Emax), mean Young's modulus (Emean), and minimum Young's modulus (Emin). We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results, focusing on their diagnostic performance for csPCa. RESULTS: Of the 359 cases, 189 were diagnosed by pathological puncture biopsy as BPH, 26 as non-csPCa, and 144 as csPCa. The PSA level, Emax, Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups (all P < 0.01), but showed no statistically significant difference between the BPH and non-csPCa groups (all P > 0.05). The area under the receiver operating characteristic curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Emax in the diagnosis of csPCa were 0.852, 143.92 kPa, 72.22%, 84.65%, 75.91%, 81.98% and 79.67%; those of Emean were 0.868, 82.42 kPa, 67.36%, 91.16%, 83.62%, 80.66% and 81.62%; and those of Emin were 0.682, 32.73 kPa, 47.22%, 89.30%, 73.91%, 71.54% and 72.14%, respectively. In the non-csPCa group, Emax, Emean and Emin were found below the optimal cut-off value in 73.08% (19/26), 92.31% (24/26) and 88.46% (23/26), respectively. CONCLUSION The stiffness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa, reduces unnecessary detection of non-csPCa, and provides some reference for its active surveillance.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Elasticity Imaging Techniques ; Retrospective Studies ; Prostate/pathology* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged

OBJECTIVE: To observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kidney yang-deficiency. METHODS: Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by randomized control method. The patients in the control group were treated with L-carnitine oral solution alone. And the patients in experimental group were treated with Huotujiji prescription. Semen volume, sperm concentration, PR, TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment. RESULTS: A total of 115 patients were included in the study, with 55 in the experimental group and 60 in the control group. In the experimental group, the sperm concentration before and after treatment were (160.71±53.7)×106/mL, (187.19±41.89)×106/mL, and PR were (20.37±9.42)%, (26.7±6.92)%, respectively. PR+NP were (32.06±8.49)% and (34.89±7.25)%. After the treatment, the sperm motility of both groups significantly improved compared to pre-treatment levels (P<0.05). And the experimental group's sperm concentration also showed a significant increase after the treatment (P<0.05). The pregnancy rate of spouses in the control group was 11.67%, which was 29.09% in the experimental group. The pregnancy rate of the spouses in the two groups showed a statistically significant difference (P<0.05). After 12weeks of treatment, the Traditional Chinese Medicine (TCM) symptom scores in the control group did not decrease significantly compared to those before treatment (P> 0.05). In contrast, the TCM symptom scores in the experimental group decreased significantly after treatment (P<0.05). Moreover, compared with the control group, the TCM symptom scores of the experimental group decreased significantly after treatment (P<0.05). CONCLUSION Huotujiji prescription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenospermia, improve the symptoms of patients, and increase the pregnancy rate of their spouses, which is worthy of clinical promotion.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Adult ; Yang Deficiency/drug therapy* ; Asthenozoospermia/drug therapy* ; Female ; Pregnancy ; Phytotherapy ; Sperm Motility ; Young Adult ; Spleen ; Treatment Outcome ; Sperm Count