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*

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.

Objective:To compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment for liver cirrhosis with esophageal gastric variceal bleeding (EGVB) and portal vein thrombosis (PVT).Methods:A total of 183 liver cirrhosis patients with EGVB and PVT in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and the First Affiliated Hospital of Wenzhou Medical University were selected from January 2017 to December 2019, and 66 patients were assigned to the endoscopic group (received endoscopi treatment) and 117 the TIPS group (received TIPS treatment). Propensity score matching was performed according to the 1∶1 ratio, yielding 58 patients in each group for analysis, with a median follow-up time of 36 months in both groups. Postoperative survival, postoperative rebleeding rate, and postoperative hepatic encephalopathy incidence were assessed using Kaplan-Meier survival curves.Results:During the follow-up, the rebleeding rate in the endoscopic group was significantly higher [39.7% (23/58) VS 17.2% (10/58), P=0.005], and the TIPS group had a higher incidence of postoperative hepatic encephalopathy [29.3% (17/58) VS 13.8% (8/58), P=0.048], and no significant difference in survival rate was observed between the two groups [74.1% (43/58) VS 75.9% (44/58), P=0.769]. In the subgroup analysis of mild degree of PVT, there was no significant difference in survival [88.0% (22/25) VS 72.0% (18/25), P=0.164], rebleeding rate [28.0% (7/25) VS 12.0% (3/25), P=0.164], or incidence of hepatic encephalopathy [8.0% (2/25) VS 20.0% (5/25), P=0.202] between the endoscopic group and the TIPS group. In the subgroup analysis of severe degree of PVT, the rebleeding rate in the endoscopic group was significantly higher than that in the TIPS group [48.5% (16/33) VS 21.2% (7/33), P=0.010], while there was no significant difference in the incidence of hepatic encephalopathy [18.2% (6/33) VS 36.4% (12/33), P=0.133], or the survival rate [63.6% (21/33) VS 78.8% (26/33), P=0.154]. Conclusion:For liver cirrhosis patients with mild PVT and EGVB, combining endoscopic therapy with anticoagulation may be superior to TIPS. Conversely, in patients with severe PVT, TIPS may be a more suitable option due to a significantly reduced rebleeding risk without a notable increase in hepatic encephalopathy incidence.

Objective To summarize the multi slice spiral computed tomography(MSCT)features of bronchiolar adenoma(BA).Methods The imaging data of 9 cases of BA confirmed by surgery and pathology were analyzed retrospectively,and relevant literature was also reviewed.Results Among the 9 cases of BA,there were 8 cases with peripheral BA(away from the pleura≤5 mm)inclu-ding 4 cases close to the pleura and 1 case in central area.BA were located in the superior lobe of the right lung in 3 cases,the middle lobe of the right lung in 2,the inferior lobe of the right lung in 2,and the inferior lobe of the left lung in 2.Five cases were solid nod-ules,2 were ground-glass nodules and other 2 were cystic cavity nodules.In 2 cases of the solid nodules,the boundary on the non-venous side was blurred.In the 1 case of the ground-glass nodule,linear and reticular shadows were observed in the lesion,accompanied by a blurred boundary.2 nodules had mild pleura indentation,and other 7 nodules were found blood vessels entering into or adhering to the lesion,3 of which were accompanied by vascular thickening.In 8 cases with 2-48 month followed up,1 cystic cavity nodule was accompa-nied by obstructive pneumonia and then inflammatory absorption,1 solid nodule enlarged accompanied by the appearance of vacuoles,and the rest 6 had no changes.One central type nodule was operated after the CT examination.Conclusion BA are mainly manifes-ted as peripheral nodules of the lung,mostly close to the pleura and away from the pleura≤5 mm.Most BA are solid nodules,and sometimes are ground-glass or cystic cavity nodules.Some nodules show blurred boundaries or inflammation on the non-venous side,and few nodules increase during follow-up,with or without small vacuoles.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.