ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome （MS）. MethodsTraditional Chinese medicine （TCM） diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis （LCA） were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes， and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included， involving 163 symptoms and signs with a total frequency of 1749； twenty-three syndrome elements were extracted， 367 times frequency in total， among which 8 syndrome elements occurred ≥10 times with 323 frequencies （88.01% of the total）. These included location-related elements such as kidney （48 times）， spleen （14 times）， and stomach （14 times）， and nature-related elements such as phlegm （71 times）， yin deficiency （64 times）， dampness （57 times）， heat （42 times）， and qi deficiency （13 times）. Based on LCA， the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm， forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified，i.e. obesity （39 times）， greasy coating （38 times）， slippery pulse （33 times）， white coating （31 times）， preference for fatty and heavy foods （30 times）， excessive urination （30 times）， fatigue and lack of strength （29 times）， wiry pulse （25 times）， and dark red tongue （25 times）. A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results， ultimately identifying obesity， greasy coating， fatigue and lack of strength， and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients （P＜0.05）. ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome， and obesity， greasy coating， fatigue and lack of strength， and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.

OBJECTIVE To summarize the current status of position training for clinical pharmacists in China and provide references for the continuous optimization of such training programs. METHODS SinoMed， CNKI，VIP and Wanfang Data were electronically searched to collect position training of clinical pharmacists studies from the inception until November 5th 2024. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS & A total of 68 pieces of relevant literature were included in the study. Among them， 50 studies reported on training content， 49 involved the allocation of teaching resources in the bases， 48 addressed training methods， and 39 focused on training evaluation； only 2 studies mentioned faculty development. There were notable variations in the clinical pharmacist training programs across different bases， particularly in the allocation of teaching resources， such as the composition of the teaching team and the utilization of auxiliary teaching tools. Additionally， differences existed in training approaches， such as those employing a single method versus a blended approach. Conversely， the core training content of each base generally revolved around clinical pharmacy practice， demonstrating a degree of consistency. Moreover， the overall emphasis on teacher training and assessment tended to be obviously insufficient. Each base can focus on enhancing the competence of clinical pharmacists by allocating teaching resources， selecting training methods， improving training content， and using evaluation tools， to further enhance the quality of clinical pharmacist training.

OBJECTIVES: To investigate the characteristics and clinical significance of anorectal manometry measurements in children with tethered cord syndrome (TCS) before and after surgery. METHODS: A retrospective study was conducted on 44 children with TCS treated at the Children's Hospital of Zhejiang University School of Medicine from January 2022 to September 2023. These patients were divided into effective subgroup (n=34) and non-effective subgroup (n=10) based on postoperative symptom improvement. Additionally, 34 children with functional constipation were selected as a control group. Baseline data and manometry measurements were compared between the preoperative TCS group and the control group, as well as between the non-effective and effective subgroups. RESULTS: The TCS group had lower short contraction time and defecation relaxation rate compared to the control group (P<0.05), while defecation residual pressure and maximum rectal tolerable threshold were higher than the control group (P<0.05). The length of the anal canal in the high-pressure zone in the effective subgroup was greater postoperatively than preoperatively (P<0.05), and the initial rectal sensation threshold decreased postoperatively (P<0.05). The non-effective subgroup had lower preoperative maximum rectal expulsion pressure compared to the effective subgroup (P<0.05). Postoperative rectal anal inhibition reflex values in the effective subgroup were higher than those in the non-effective subgroup (P<0.05). CONCLUSIONS There are some differences in anorectal dynamics between children with TCS and those with functional constipation. Maximum rectal expulsion pressure may be a key predictor of surgical outcomes. Surgery can alter certain defecation functions in some children.
Humans ; Male ; Anal Canal/physiopathology* ; Female ; Rectum/physiopathology* ; Child ; Child, Preschool ; Retrospective Studies ; Manometry ; Neural Tube Defects/physiopathology* ; Infant ; Defecation ; Adolescent ; Constipation/physiopathology* ; Clinical Relevance

Transformer models have emerged as pivotal tools within the realm of drug discovery, distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes. Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data, these models showcase remarkable efficacy across various tasks, including new drug design and drug target identification. The adaptability of pre-trained transformer-based models renders them indispensable assets for driving data-centric advancements in drug discovery, chemistry, and biology, furnishing a robust framework that expedites innovation and discovery within these domains. Beyond their technical prowess, the success of transformer-based models in drug discovery, chemistry, and biology extends to their interdisciplinary potential, seamlessly combining biological, physical, chemical, and pharmacological insights to bridge gaps across diverse disciplines. This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields. In our review, we elucidate the myriad applications of transformers in drug discovery, as well as chemistry and biology, spanning from protein design and protein engineering, to molecular dynamics (MD), drug target identification, transformer-enabled drug virtual screening (VS), drug lead optimization, drug addiction, small data set challenges, chemical and biological image analysis, chemical language understanding, and single cell data. Finally, we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

Objective:To analyze the electrocardiographic characteristics of patients with chronic pulmonary artery stenosis (PAS), and to explore their relationship with disease severity indicators.Methods:The study was a retrospective case-series analysis. Patients with chronic PAS admitted to Gansu Provincial Hospital from January 2018 to July 2021 were enrolled. The clinical data and the results of electrocardiography, transthoracic echocardiography, right cardiac catheterization, N-terminal B-type natriuretic peptide (NT-proBNP) measurement and 6-min walking distance test of patients were analyzed. The linear regression model or logistic regression model was used to analyze the relationship between electrocardiographic characteristics and the disease severity in patients with chronic PAS.Results:Sixty-three patients aged (62.1±9.7) years including 43 females (68.3%) were enrolled in the study. Among them, 62 patients (98.4%) had (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ)<1.5 mV, and no patients had V 5lead R: S ratio to V 1 lead R: S<0.04 and V 6 lead R: S ratio<0.4. There were 55 patients (87.3%), with flat or inverted T-waves in V 1, and 10 patients (15.9%) with flat or inverted T-waves in all precordial leads (V 1-V 6). There were 18 patients (28.6%) with flat or inverted T-waves in inferior leads (Ⅱ, Ⅲ, aVF). Multiple liner regression analysis showed that Max R V1, 2+Max S I, aVL-S V1 combined with the number of flat or inverted T-waves in limb leads was independently correlated with atrial area ( R2=0.290, P=0.002); R V1+S V5 was independently correlated with right ventricular area ( R2=0.257, P=0.001); R peak V 1 combined with the number of flat or inverted T waves in precordial leads was independently correlated with tricuspid annular plane systolic excursion ( R2=0.407, P<0.001); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) combined with the number of flat or inverted T waves in precordial leads was independently correlated with NT-proBNP ( R2=0.504, P<0.001); Max R V1, 2+Max S I, aVL-S V1 were independently correlated with right atrial pressure ( R2=0.803, P=0.036); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) were independently correlated with mean pulmonary artery pressure ( R2=0.302, P<0.001); R aVRcombined with the number of flat or inverted T-waves in precordial leads was independently correlated with cardiac index ( R2=0.173, P=0.003); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) was independently correlated with pulmonary vascular resistance ( R2=0.173, P=0.002); R peak V 1 combined with the number of flat or inverted T-waves in precordial leads was independently correlated with mixed vein oxygen saturation ( R2=0.302, P<0.001). Conclusion:The vast majority of patients with chronic PAS have (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ)<1.5 mV and flat or inverted T-wave in V 1 lead, and some characteristic electrocardiographic manifestations are correlated with indicators of disease severity.

Objective:To compare and analyze the clinical characteristics of acute myeloid leukemia (AML) related to the treatment of hematological tumors and solid tumors.Methods:The laboratory and clinical data of 41 patients with treatment-related AML (t-AML) in the Department of Hematology, Henan Cancer Hospital from January 2014 to December 2021 were retrospectively analyzed, and they were divided into hematological tumor group and solid tumor group. Survival analysis was performed using the Kaplan-Meier method and Log rank test.Results:The median interval from the first tumor diagnosis to t-AML in 41 patients was 21.0 (16.5-46.0) months; 24 (58.5%) had abnormal expression of lymphoid antigen, 28 (68.3%) had abnormal karyotype, 18 cases (43.9%) were positive for fusion gene, and 28 cases (68.3%) were positive for gene mutation; the median recurrence-free survival (RFS) was 11.0 months, and the median overall survival (OS) was 11.5 months. The proportion of acute promyelocytic leukemia ([APL], 0.0, 0/13), complete response ([CR],18.2%, 2/11), median OS (4.5 months) and median RFS (2.5 months) of t-AML patients in the hematological tumor group were significantly lower than those in the solid tumor group (35.7%, 10/28; 68.0%, 17/25; not reach; not reach), but the proportion of M4 /M5 (93.2%,12/13) was significantly higher than that in the solid tumor group (53.6%,15/18; all P values<0.05). Through subgroup analysis, the proportion of patients with positive PML-RARa and good prognosis karyotypes in the solid tumor group (35.7%, 10/28; 46.4%, 13/28) was significantly higher than that in the hematological tumor group (0.0, 0/13; 0.0, 0/13; P<0.05), while the proportion of patients with intermediate karyotypes (42.9%, 12/28) was significantly lower than that in the hematological tumor group (84.6%, 11/13; P<0.05), the difference was statistically significant. The CR rate (90.0%, 9/10), median OS (not reach) and median RFS (not reach) in the t-APL group were higher than those in the t-AML (without t-APL) group (38.5%, 10/26; 6 months; 8 months; P<0.05). After excluding the effect of t-APL patients, there was no significant difference in the CR rate, median OS and median RFS between the solid tumor group (8; 9 months; not reach) and the hematological tumor group (2; 4 months; 2 months; P>0.05). Univariate analysis showed that the primary tumor belongs to hematological tumor was a common risk factor for OS and RFS in t-AML patients ( P<0.10). Conclusions:Compared with patients with t-AML secondary to solid tumors, patients with t-AML secondary to hematological tumors have poorer treatment effects and poorer prognosis. After excluding the effect of t-APL patients, there are no significant differences in the treatment efficacy and prognosis between the two types of t-AML patients.

Objective To investigate the effects of remazolam on melatonin secretion,sleep rhythm and postoperative delirium(POD)in elderly patients undergoing spinal surgery.Methods A total of 160 elderly patients,76 males and 84 females,aged 65-80 years,BMI 18.5-24.0 kg/m2,ASA physical status Ⅱ or Ⅲ,from November 2023 to January 2024 undergoing spinal surgery(lumbar interbody fusion,posterior approach)under general anesthesia were selected.The patients were divided into two groups by random number table method:the remazolam group(group R)and the propofol group(group P),80 pa-tients in each group.Group R was given remazolam 0.3 mg/kg for anesthesia induction,and then continued to pump remazolam 0.3-0.8 mg·kg-1·h-1 for anesthesia maintenance.Group P was given propofol 2.0 mg/kg for anesthesia induction,and then continued to pump propofol 4-6 mg·kg-1·h-1 for anesthesia maintenance.The levels of melatonin and cortisol were recorded at 04:00 a.m.on the day of surgery,1 day,2 and 3 days after surgery.Pittsburgh sleep quality index(PSQI)and VAS pain scores at rest were recorded 1 day before surgery,1 day and 2 days after surgery and before discharge.The occurrence of POD and post-operative sleep disorder(POSD)were recorded.The duration of extubation,PACU stay time,total analgesia pump compressions,effective analgesia pump compressions,number of remedial analgesia cases,intraoperative hypotension,postoperative nausea and vomiting,dizziness,respiratory depression and other adverse events were recorded.Results Compared with group P,the extubation time and PACU residence time in group R were significantly shortened(P＜0.05),the level of melatonin was significantly increased while the level of cortisol was significantly decreased at 4:00 a.m.,and the PSQI was significantly decreased 1 day after surgery(P＜0.05),the incidence of POD,POSD,and intraoperative hypotension were signifi-cantly decreased(P＜0.05).There were no significant differences in extubation time,total and effective times of analgesic pump,rate of remedial analgesia,intraoperative hypotension,postoperative nausea,vom-iting,dizziness and respiratory depression between the two groups.Conclusion Remazolam has little effect on the secretion rhythm of melatonin and cortisol and the sleep rhythm after spinal surgery in elderly pa-tients,and the recovery is faster,which can reduce the incidence of POD and alleviate the sleep disorder af-ter spinal surgery.

Objective·To investigate the effects of sennoside A(SA)on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine(5-HT)and its receptor in mice with diabetes mellitus type 2(T2DM).Methods·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups,namely the model group and the model+SA group,with six mice in each group.Six C57BL/6J mice with the same genetic background were used as the control group.The control group was fed with normal diet,and the model group and the model+SA group were given intraperitoneal injection of streptozotocin(30 mg/kg)daily on the basis of high-fat diet to establish a model of T2DM.The model+SA group was given SA daily by gavage for 8 weeks,and the control group and the model group were given equal volume of distillation-distillation H2O by gavage.The body weight,fasting blood glucose(FBG)and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment.The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin(H-E)staining,and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit.Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B(HTR2B)and serotonin transporter(SERT)in thoracic aorta of mice.Results·Compared with the control group,the body weight,FBG and 2-h postprandial blood glucose in the model group increased,and glucose metabolism was disordered.The expression of HTR2B and SERT protein in thoracic aorta increased,while the concentration of 5-HT in thoracic aorta decreased.The serum 5-HT concentration increased(all P<0.05).After treatment with SA,compared with the model group,the body weight of the model+SA group decreased,and FBG and 2-h postprandial blood glucose were significantly improved.The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased,while the concentration of 5-HT increased.The serum 5-HT concentration decreased(all P<0.05).Conclusion·SA can reduce atherosclerotic plaque area in T2DM mice,which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

Objective To explore the effect of chenodeoxycholic acid(CDCA)on the expression of glucagon-like peptide-1(GLP-1)in the intestine of mice induced by high-fat diet(HFD)through farnesoid X receptor(FXR),and investigate the related mechanism.Methods Forty C57BL/6 mice were divided into control group,HFD group,HFD+CDCA group,HFD+Z-Gug(FXR antagonist)group,and HFD+CDCA+Z-Gug group,with 8 animals in each group.During intervention for 8 weeks,body weight and 24-hour food intake were measured every week.At the 8th week,oral glucose tolerance test(OGTT)and intraperitoneal glucose tolerance test(IPGTT)were conducted.After the mice were sacrificed,the serum levels of GLu,TG,CHO,LDL-C and HDL-C were detected;the expression levels of GLP-1 and FXR in intestinal tissues were detected by immunofluorescence assay;and the mRNA levels of TNF-α,IL-6,IL-1β,Gcg and FXR were detected by RT-qPCR;the serum level of GLP-1 was detected by ELISA,and the proportion of intraepithelial lymphocytes(IELs)subsets and the expression of CD26/DPP4 were detected by flow cytometry.Results Compared with the control group,the HFD group had increased body weight,abnormal serum glucose and lipid metabolism,impaired oral glucose tolerance,and weakened secretion of gastrointestinal hormones(P＜0.05),enhanced FXR expression at mRNA and protein levels,declined Gcg mRNA level and GLP-1 secretion level(P＜0.05),increased mRNA levels of intestinal inflammatory factors TNF-α,IL-6 and IL-1β(P＜0.05),raised proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs,and TCRαβ+CD8αβ+IELs but reduced proportion of TCRγδ+IELs,and increased total CD26/DPP4 expression in IELs(P＜0.05).Compared with the HFD group,HFD+CDCA treatment resulted in significantly increased body weight,impaired oral glucose tolerance,decreased secretion of gastrointestinal hormones,increased FXR mRNA and protein expression,and decreased Gcg mRNA expression and GLP-1 secretion(P＜0.05);decreased proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs and TCRααβ+CD8αβ+IELs but increased proportion of TCRγδ+ cells in IELs,and increased expression of total CD26/DPP4 in IELs(P＜0.05),which were significantly improved after Z-Gug intervention(P＜0.05).Conclusion CDCA may inhibit the expression and secretion of GLP-1 in intestinal tissue by activating FXR,and reduce the secretion of GLP-1.At the same time,CDCA may inhibit the expression of related inflammatory factors,regulate the proportions of IELs subsets,up-regulate the expression level of CD26/DPP4,promote the degradation of GLP-1 and aggravate insulin resistance.