Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

This study aimed to investigate the associations between the post-wash total progressively motile sperm count (TPMSC) in the first intrauterine insemination (IUI) cycle and pregnancy outcomes of the second IUI cycle. Data were retrieved from the clinical database at the Reproductive Center of Peking University Third Hospital (Beijing, China) between January 2011 and December 2022. Couples were included in this retrospective cohort study if they had unexplained or mild male factor infertility and were treated with IUI for two consecutive cycles using the same protocol. A total of 8290 couples were included in the analysis. The mean ± standard deviation (s.d.) age of women was 32.0 ± 3.5 years. We categorized groups based on the post-wash TPMSC (×10 6 ) levels in the first IUI cycle: group 1 (0 < TPMSC < 1, n = 1290), group 2 (1 ≤ TPMSC < 2, n = 863), group 3 (2 ≤ TPMSC < 3, n = 800), group 4 (3 ≤ TPMSC < 4, n = 783), group 5 (4 ≤ TPMSC < 5, n = 1541), group 6 (5 ≤ TPMSC < 6, n = 522), group 7 (6 ≤ TPMSC < 7, n = 547), group 8 (7 ≤ TPMSC < 8, n = 175), group 9 (8 ≤ TPMSC < 9, n = 556), group 10 (9 ≤ TPMSC < 10, n = 192), and group 11 (TPMSC ≥ 10), n = 1021). The primary outcome was live birth rate of the second IUI cycle. Live birth rates were 7.9%, 5.8%, 7.6%, 7.4%, 7.3%, 8.4%, 7.5%, 7.4%, 8.8%, 8.9%, and 7.6% in each group, respectively. There were no statistically significant differences in clinical pregnancy rates or live birth rates between any groups and those with the post-wash TPMSC <1 × 10 6 . In an IUI program for unexplained and mild male factor infertility, the post-wash TPMSC in the first IUI cycle was not significantly associated with the live birth rate in the second IUI cycle.
Humans ; Female ; Male ; Pregnancy ; Adult ; Retrospective Studies ; Sperm Count ; Pregnancy Rate ; Sperm Motility/physiology* ; Insemination, Artificial/methods* ; Pregnancy Outcome ; Infertility, Male/therapy* ; Insemination, Artificial, Homologous ; Live Birth

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the distribution of the traditional Chinese medicine(TCM)constitution types in the patients with nonspecific low back pain(NLBP)and to explore the correlation of the thickness of ligamentum flavum with the age,body mass index(BMI),gender,the presence of diabetes mellitus,and the grading of hypertension.Methods Sixty patients with NLBP admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to June 2023 were selected as the study subjects.The TCM constitution types of the patients were identified,the thickness of the ligamentum flavum at lumbar vertebrae 4/5 segment(L4/5)disc level was measured by computerized tomography(CT)scanning,and the patients'age,genders,TCM constitution types,BMI,the presence or absence of diabetes mellitus,and hypertension grading were recorded.Correlation analysis and linear regression analysis were used for the exploration of the relevant influencing factors for the thickness of the ligamentum flavum of patients with NLBP.Results(1)The average thickness of ligamentum flavum in the 60 patients with NLBP was(2.60±0.72)mm.(2)The TCM constitutions of NLBP patients were classified into four types,of which blood stasis constitution was the most common,accounting for 21 cases(35.0%),followed by 19 cases(31.7%)of damp-heat constitution,12 cases(20.0%)of phlegm-damp constitution,and 8 cases(13.3%)of qi deficiency constitution.(3)The results of correlation analysis showed that BMI,gender,TCM constitution type and the presence or absence of diabetes mellitus had no influence on the thickness of ligamentum flavum in NLBP patients(P＞0.05),while the age and hypertension grading had an influence on the thickness of ligamentum flavum(P＜0.01).(4)The results of linear regression analysis showed that the age had an influence on the thickness of the ligamentum flavum(b = 0.034,t = 6.282,P＜0.01),while the influence of the hypertension grading had no influence on the thickness of the ligamentum flavum(P＞0.05).Conclusion The TCM constitution type of NLBP patients is predominated by blood stasis constitution,the thickness of ligamentum flavum is significantly affected by the age,and hypertension may be a potential factor affecting the thickness of ligamentum flavum.

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

AIM To screen anti-inflammatory activity Q-markers for Glycyrrhizae Radix et Rhizoma.METHODS Lipopolysaccharide was used for stimulating RAW264.7 macrophages to establish inflammatory model,after which the NO inhibitory rates of different grades of medicinal materials were determined.The UHPLC-QTOF-MS fingerprints were established,after which chemical constituents were identified,heatmap was drawn,and orthogonal partial least squares analysis was performed.RESULTS Grade 1 and grade 2 medicinal materials demonstrated higher NO inhibitory rates than gradeless and uniformly-priced goods(P＜0.05,P＜0.01).There were 211 common peaks in the fingerprints of 47 batches of medicinal materials,total 56 compounds were identified,containing 17 saponins,6 flavonoids,8 flavanones,4 chalcones,12 isoflavones and 9 other kinds.The relative contents of isoflavones,coumarins,kaempferol and licoflavonol in grade 1 and grade 2 medicinal materials were higher than those in gradeless and uniformly-priced goods,while the relative contents of flavanones,chalcones and saponins in wild products were higher than those in cultivated products.Neoliquiritin,isoliquiritin,kaempferol,hedysarimcoumestan E,licorice saponin C2,licoarylcoumarin,glicoricone and liconeolignan were taken as Q-markers.CONCLUSION This stable and reliable method has a certain reference value for the quality control of Glycyrrhizae Radix et Rhizoma.

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.
Gas Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry