BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L~(-1).
Fruit/chemistry* ; Morinda/chemistry* ; Synoviocytes ; Cell Proliferation ; Arthritis

Objective:To investigate the effects of anxiety and depressive symptoms in mediation of pain catastrophizing on disability in patients with low back pain.Methods:A cross-sectional survey was conducted among 97 patients with low back pain in the Changjiang Subdistrict community health center from July to October 2021. Oswestry Disability Index, pain catastrophic subscale in Coping Strategies Questionnaire-24, Generalized Anxiety Disorder Scale-short version, Patient Health Depression Questionnaire-short version were used to evaluate the activity dysfunction, pain catastrophic cognition and anxiety and depression levels of patients,respectively. Path analysis was implemented to test the mediation model, and the indirect effects were assessed using the bootstrap procedure with bias-corrected 95 %CI. Results:Results suggested significant positive correlations among pain catastrophizing, anxiety, depressive symptoms and disability of patients. In addition, both anxiety and depressive symptoms significantly mediated the impact of pain catastrophizing on disability (standardized indirect effects were 0.183 and 0.197, P<0.05). Patients with higher levels of pain catastrophic cognition showed higher levels of anxiety and depressive symptoms (β=0.757, 0.720; P<0.01), and reported more severe motor dysfunction (β=0.241, 0.274; P<0.05). Conclusions:Our findings suggest that anxiety and depression may be the psychological pathways through which pain catastrophizing predicts disability in patients with low back pain. Effective psychological interventions, such as emotion regulation and stress reduction strategies should be considered in treatment and supportive care for patients with low back pain.

The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

Objective: To study the factors affecting the survival and prognosis of patients with intracranial ependymoma. Methods:From January 2008 to January 2018, the prognoses of 276 patients with intracranial ependymoma were analyzed using Log-rank and Cox model analysis. The variables included sex, age, tumor location, tumor diameter, resection extent, pathological grade, Ki-67 index, postoperative radiotherapy, and postoperative chemotherapy. Results: Tumor location, resection extent, and postoperative radiothera-py could all affect the overall survival (OS) and progression-free survival (PFS) of patients with intracranial ependymoma (P<0.001) and independently affected the OS (P<0.001, P<0.001, and P=0.002, respectively) and PFS (P<0.001, P<0.001, and P=0.001, respectively). The Ki-67 index was an independent factor affecting PFS in patients with intracranial ependymoma (P<0.001). The supratentorial loca-tion and Ki-67 index≥10% were independent risk factors indicating poor prognosis (P<0.001). Total resection and postoperative radio-therapy were protective factors (P<0.001 and P=0.001, respectively). Conclusions: Tumor location, resection extent, Ki-67 index, and postoperative radiotherapy are independent factors affecting the prognosis of intracranial ependymoma. It is helpful to extend the PFS and OS of patients through complete tumor resection or postoperative radiotherapy.

BACKGROUNDGastrojejunostomy (GJJ) and endoscopic stenting (ES) are palliative treatments for gastric outlet obstruction (GOO) caused by gastric cancer. We compared the outcomes of GJJ with ES by performing a meta-analysis.

METHODSClinical trials that compared GJJ with ES for the treatment of GOO in gastric cancer were included in the meta-analysis. Procedure time, time to resumption of oral intake, duration of hospital stay, patency duration, and overall survival days were compared using weighted mean differences (WMDs). Technical success, clinical success, procedure-related mortality, complications, the rate of re-obstruction, postoperative chemotherapy, and reintervention were compared using odds ratios (OR s).

RESULTSNine studies were included in the analysis. Technical success and clinical success were not significantly different between the ES and GJJ groups. The ES group had a shorter procedure time (WMD = -80.89 min, 95% confidence interval [CI] = -93.99 to -67.78,P < 0.001), faster resumption of oral intake (WMD = -3.45 days, 95% CI = -5.25 to -1.65,P < 0.001), and shorter duration of hospital stay (WMD = -7.67 days, 95% CI = -11.02 to -4.33,P < 0.001). The rate of minor complications was significantly higher in the GJJ group (OR = 0.13, 95% CI = 0.04-0.40,P < 0.001). However, the rates of major complications (OR = 6.91, 95% CI = 3.90-12.25,P < 0.001), re-obstruction (OR= 7.75, 95% CI = 4.06-14.78,P < 0.001), and reintervention (OR= 6.27, 95% CI = 3.36-11.68,P < 0.001) were significantly lower in the GJJ group than that in the ES group. Moreover, GJJ was significantly associated with a longer patency duration (WMD = -167.16 days, 95% CI = -254.01 to -89.31,P < 0.001) and overall survival (WMD = -103.20 days, 95% CI = -161.49 to -44.91, P= 0.001).

CONCLUSIONSBoth GJJ and ES are effective procedures for the treatment of GOO caused by gastric cancer. ES is associated with better short-term outcomes. GJJ is preferable to ES in terms of its lower rate of stent-related complications, re-obstruction, and reintervention. GJJ should be considered a treatment option for patients with a long life expectancy and good performance status.

Gastric Bypass ; methods ; Gastric Outlet Obstruction ; mortality ; therapy ; Gastroscopy ; methods ; Humans ; Palliative Care ; Postoperative Complications ; etiology ; Publication Bias ; Stents ; Stomach Neoplasms ; complications

Objective To investigate the efficacy and safety of paroxe-tine combined with low dose of quetiapine in the treatment of generalized anxiety disorder.Methods One hundred and forty patients with gener-alized anxiety disorder were randomly assigned to treatment group ( parox-etine combined with low dose of quetiapine group , n =71 ) and control group ( paroxetine group , n =69 ).The efficacy was assessed by the Hamilton rating scale for anxiety ( HAMA ) , the Treatment Emergent Symptom Scale ( TESS ) for side effects , and Pittsburgh sleep quality in-dex(PSQI)for sleep qualities of all participants at baseline and at the end of 1st, 2nd, 4th, 6th, 8thweek.Results There were no significant differ-ences between two groups at cure rate ( 70.4%/68.1%) , notable im-provement rate ( 15.5%/13.0%) , progress rate ( 8.5%/10.1%) , and ineffective rate ( 5.6%/8.7%) overall the treatment course.Compare with the baseline , the treatment group showed notable decrease of HAMA at the 1 st weekend ( P<0.05 ) , and the control group showed that at the 2nd weekend (P<0.05).The treatment group had a more significant de-crease than the control group at the 1st, 2nd, and 4th week end(P<0.05 or P<0.01 ).The psychic anxiety score of the treatment group at the 1st, 2nd, 4th weekend and the somatic anxiety score at the 2nd, 4th weekend showed significant decrease ,compared with the control group ( P<0.05 or P<0.01 ).Both of the two group had no serious adverse events.Conclusion Paroxe-tine combined with low dose of quetiapine is an effective and safe way to treat generalized anxiety disorder , and patients have good compliance under the treatment.