Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective To observe the value of diffusion kurtosis imaging(DKI)radiomics for evaluating Parkinson disease(PD).Methods Totally 76 PD patients(PD group)and 80 healthy controls(HC group)were retrospectively analyzed.The subjects were divided into training set(n=125,including 61 PD and 64 HC)and test set(n=31,including 15 PD and 16 HC)at the ratio of 8:2.ROI of bilateral substantia nigra,caudate nucleus,putamen,globus pallidus and thalamus were automatically delineated on mean kurtosis(MK)images of cerebral DKI.The mean MK values(MKmean)of the above ROIs were obtained and compared between groups.Support vector machine(SVM)model was constructed based on 50 selected optimal texture features.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for evaluating PD.Results MKmean of bilateral substantia nigra,caudate nucleus and thalamus in PD group were all significantly lower than those in HC group(all P＜0.05).No significant difference of MKmean of bilateral putamen nor globus pallidus was found between groups(all P＞0.05).The sensitivity,specificity,accuracy and AUC of SVM model for evaluating PD in training set was 86.89％,93.75％,90.40％and 0.982,respectively,which in test set was 86.67％,93.75％,90.32％and 0.958,respectively.Conclusion DKI radiomics could be used to effectively evaluate PD through description of microstructural changes of cerebral nuclei.

ABSTRACT OBJECTIVE To investigate the use of spironolactone tablet in children's hospital, and to explore the feasible scheme that can improve the current dosage distribution of spironolactone tablets, so as to meet the needs of precise and individualized clinical administration of pediatric patients. METHODS All the prescriptions including spironolactone tablet (20 mg per tablet) were obtained from 1st January 2021 to 31th December 2022 in Children's Hospital, Zhejiang University School of Medicine. The children's age, splitting specification, department distribution and problems of common tablet splitting were analyzed, appropriate countermeasures were explored according to literature and team practice. RESULTS A total of 11 239 spironolactone tablet prescriptions were included, among which, the proportion of splitting was 83.91%; in the splitting prescriptions, it showed the characteristics of young age, multi-dose specifications, strong drug specialization and long drug duration. Formulating the practice specification for manipulation of drugs, with the right dosing tool, contribute to improve the accuracy of manipulation of drugs and reduce adverse events caused by incorrect dosing; while, the exploration of extemporaneous liquid preparations and preparations in medical institutions, contributed to improve the accuracy and stability of dosing, and realize individualized drug delivery. CONCLUSION In this study, exploring the appropriate dosage regimen for spironolactone tablet as an example, feasible countermeasures with accurate fractional dose, controllable quality and high compliance of children are explored in combination with team practice and literature retrieval analysis, which is based on the actual clinical needs, so as to provide reference for finding appropriate fractional dose administration schemes for pediatric tablets.

Objective:To analyze the clinical features, treatment, and outcomes of fetal/neonatal atrial flutter (AFL) at the onset of the perinatal period to improve the management of this condition.Methods:This retrospective study analyzed the clinical data, treatment, and follow-up results of fetal/neonatal AFL cases transferred to Shanghai Children's Medical Center from November 2013 to August 2021. Clinical characteristics, cardioversion procedures, and outcomes were summarized. Descriptive method was used for statistical analysis.Results:A total of 21 fetuses/neonates presenting with AFL in the perinatal period were involved in this study, including 17 males and four females. Ten of them were born at full term, and 11 were preterms. All of the patients were delivered by cesarean section at 32 to 41 gestational weeks [ (36.6±1.9) weeks] with a birth weight of 2 130 to 4 450g [ (3 059±528) g]. Increased fetal heart rate was all detected after 32 weeks of gestation, and three of them were diagnosed with AFL by fetal echocardiography before being born. The heart rate remained elevated in all cases after birth. All were diagnosed as AFL based on an electrocardiogram on the day of birth, which showed a 2 to 6 over one ratio of atrioventricular conduction. Among the six cases of cardiac insufficiency and low blood pressure complicated by dyspnea and cyanosis, the symptoms were relieved in four cases after mask oxygenation and two cases after ventilation. Among the 21 cases, one was converted spontaneously to normal sinus rhythm and the other 20 recovered after medication or electrical cardioversion. Seven cases were initially treated by drug conversion with a success rate of 5/7 and hospitalized for 23 d (13-25 d). There was one with cardiac insufficiency before treatment and three newly developed cardiac insufficiency during treatment among the seven cases. Thirteen cases were offered electrical cardioversion initially, and the success rate of cardioversion was 12/13. There were five cases of cardiac insufficiency before treatment, while no new cases of cardiac insufficiency was reported during treatment. The duration of hospitalization was 11 d (9-14 d). Apart from one case, the rest 20 infants were followed up from one month to eight years old, and no recurrence was reported.Conclusions:For fetal/neonatal AFL with the onset during the perinatal period, the symptoms mainly manifest in late pregnancy. Its diagnosis depends on fetal echocardiography before birth or electrocardiogram after birth, and electrical cardioversion is a fast and effective measure. While the prognosis of perinatal-onset AFL is generally good.

This article reports a rare Crohn′s disease (CD) case complicated with deep vein thrombosis and Guillain-Barre syndrome (GBS). Through the diagnosis and treatment of the multidisciplinary team, the condition of patient is relieved with no recurrence. Prevention of venous thromboembolism, rare extraintestinal manifestations and rare side adverse of anti-tumor necrosis factor-α monoclonal antibodies and their mechanisms in CD patients were discussed for reference.

This article reports a rare Crohn′s disease (CD) case complicated with deep vein thrombosis and Guillain-Barre syndrome (GBS). Through the diagnosis and treatment of the multidisciplinary team, the condition of patient is relieved with no recurrence. Prevention of venous thromboembolism, rare extraintestinal manifestations and rare side adverse of anti-tumor necrosis factor-α monoclonal antibodies and their mechanisms in CD patients were discussed for reference.

ObjectiveTo evaluate the effects of transcranial direct current stimulation (tDCS) on post-stroke aphasia (PSA). MethodsLiteratures about tDCS for PSA were retrieved from PubMed, Web of Science, Cochrane library, Embase CNKI and Wanfang Data, until December, 2021. The contents of the author, publication time, subjects, intervention methods and time, main outcome indicators and conclusions were extracted. ResultsA total of 1 026 articles were returned and 45 articles were finally included. The publication time was from 2010 to 2021. The subjects of the study were patients with PSA. The main outcome indicators were the various speech scales and their sub-items. For most of the trials, scores of the scales were better in the experimental groups than in the control groups after treatment, and a few found little improvement in Boston Diagnostic Aphasia Examination, or only improved in complex language tasks. tDCS can improve the repetition, naming, spelling and verbal fluency of PSA patients, which might relate with electrode placement, current magnitude, duration, intensity and left cortical integrity. ConclusiontDCS is effective on different language sub-items of PSA, and various with the program of tDCS.

ObjectiveBy comparing the difference of volatile components of the decoction pieces before and after being processed by braising method of Jianchangbang and steaming method included in the 2020 edition of Chinese Pharmacopoeia， the influence of processing methods on the flavor formation of Polygoni Multiflori Radix （PMR） was compared. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components of 30 batches of PMR samples from 3 origins with 3 processing methods. The GC was performed under programmed temperature （starting temperature of 40 ℃， rising to 150 ℃ at 5 ℃·min^-1， and then rising to 195 ℃ at 10 ℃·min^-1） with high purity helium as carrier gas and the split ratio of 10∶1. Mass spectrometry conditions were electron impact ion source （EI） and the detection range of m/z 50-650， the peak area normalization method was used to calculate the relative mass fraction of each component. The chromaticity values of different processed products were measured by a precision colorimeter， the relationship between chromaticity values and relative contents of volatile components was investigated by OriginPro 2021， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed on the sample data by SIMCA14.1. The differential components of different processed products of PMR were screened according to the principle of variable importance in the projection （VIP） value>1.5， and the material basis of different odor formation of PMR and its processed products was explored. ResultA total of 59 volatile components were identified， among which 34 were raw products， 33 were braised products， and 27 were steamed products. PCA and OPLS-DA results showed that there were significant differences between the three， but there was no significant difference between samples from different origins of the same processing method. Color parameters of a^*， b^*， E^*ab had no significant correlation with contents of volatile components， while L^* was negatively correlated with contents of 2-methyl-2-butenal， 2-methyltetrahydrofuran-3-one and 2，3-dihydro-3，5-dihydroxy-6-methyl-4（H）-pyran-4-one （P<0.05）. The contents of pungent odor components such as caproic acid， nonanoic acid and synthetic camphor decreased after processing， while the contents of sweet flavor components such as 2-methyl-2-butenal， furfural and 5-hydroxymethylfurfural increased after processing， and the contents of furfural， 5-methyl-2-furanmethanol， 5-hydroxymethylfurfural and other aroma components in the braised products were significantly higher than that in the steamed products. ConclusionHS-GC-MS can quickly identify the volatile substance basis that causes the different odors of PMR and its processed products. The effect of processing methods on the odor is greater than that of origin. There is a significant correlation between the color parameter of L^* and contents of volatile components， the "raw" taste of PMR may be related to volatile components such as caproic acid， pelargonic acid and synthetic camphor， the "flavor" after processing may be related to the increase of the contents of 2-methyl-2-butenal， furfural， 5-hydroxymethylfurfural， methyl maltol and furfuryl alcohol.

42 cases with gastroesophageal varices were prospectively included. The groups were treated with endoscopic band ligation or combined with tissue adhesive. The results showed that the left gastric vein internal diameter, average blood flow velocity and blood flow volume after the treatment of band ligation combined with tissue adhesive were significantly lower than that of the treatment of band ligation alone, and the differences were statistically significant ( P < 0.05). Spleen and portal vein internal diameter, blood flow and average velocity, the liver and spleen size, shear wave velocity and liver function grade of the two groups after treatment did not change significantly ( P > 0.05). The effective rate of band ligation combined with tissue adhesive in the treatment of esophageal and gastric varices (66.67%, 52.38%) were higher than that of band ligation alone (42.85%, 23.81%) ( P > 0.05), and the re-bleeding rate of the latter was higher (9.52% and 19.05%, P > 0.05). Hence, it is suggested that the combined therapy is safe and more effective, and has no apparent effect on liver function and portal hypertension.