Parenteral n-3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn's disease after bowel resection: a randomized, unblinded controlled clinical trial.

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Butyrate Prevents the Pathogenic Anemia-Inflammation Circuit by Facilitating Macrophage Iron Export.

Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron-mediated, pathogenic anemia-inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short-chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis-induced anemia but also reduces TNF-α production in macrophages. Consistently, macrophage-conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti-TNF-α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.

Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

[Precise application of Beichaihu and Nanchaihu in classical formulas].

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.

An observational study of the effects of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on postoperative complications in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease. Most patients with CD require surgery but exhibit an elevated incidence of postoperative complications. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are considered beneficial for nutrition, anti-inflammation, immunity, and intestinal microflora balance in humans. This study assessed the effects of ω-3 PUFA-supplemented parenteral nutrition (PN) on postoperative complications in CD patients. METHODS: Overall, 186 CD patients undergoing bowel resection were recruited for this study. The patient data were collected from a prospectively maintained database. After surgery, 83 patients received ω-3 PUFA-supplemented PN, and 103 did not. The postoperative complications were compared between the groups. Complication risk factors were identified by univariate and multivariate analyses. RESULTS: Patients who received ω-3 PUFA-supplemented PN after surgery had lower C-reactive protein (CRP) levels on postoperative day 3 (57.2±5.3 vs. 43.5±3.9 mg/L, P=0.047) and shorter postoperative hospital stays (12.1±1.1 vs. 9.3±0.6 days, P=0.041) than those who did not. The ω-3 PUFA group exhibited significantly fewer overall complications (40.8% vs. 24.1%, P=0.016) and major complications (23.3% vs. 9.6%, P=0.014) than the control group. Postoperative complications were associated with infliximab, ω-3 PUFAs, CRP levels, operative time, and laparoscopic surgery. The multivariate regression revealed that preoperative infliximab use was a positive risk factor and postoperative ω-3 PUFA-supplemented PN was a negative risk factor for postoperative complications. CONCLUSIONS: ω-3 PUFA-supplemented PN reduced post-surgery inflammatory response of CD patients, which in turn decreased the postoperative complications and accelerated recovery.

Electroacupuncture Enhances Gastric Accommodation via the Autonomic and Cytokine Mechanisms in Functional Dyspepsia.

BACKGROUND: Due to complex pathophysiology of functional dyspepsia, medications to treat functional dyspepsia are not effective for all patients. Transcutaneous electrical acustimulation (TEA) is an potentially effective therapy for functional dyspepsia without proofs of definite mechanisms. AIMS: We aimed to investigate the therapeutic impacts of TEA on postprandial distress syndrome (PDS) and explore potential neuroimmune mechanisms. METHODS: We conducted a double-blinded, randomized, controlled trial in 30 PDS patients randomized for 4-week TEA or sham-TEA. Dyspeptic symptoms, gastric accommodation, gastric emptying and heart rate variability (HRV) were assessed. Duodenal mucosal inflammation was also evaluated. RESULTS: The dyspeptic symptoms were improved with TEA compared with sham-TEA (P = 0.03). The initial satiety volume and the maximum tolerable volume (MTV) were both improved after the TEA treatment, compared with the sham-TEA group (P all < 0.05). The gastric emptying time (T1/2) was not altered with TEA or sham-TEA. The TEA treatment increased vagal activity and decreased sympathovagal ratio assessed by HRV (P all < 0.01). The IL-6 expression in bulb mucosa was downregulated by the TEA treatment compared to the baseline (P < 0.05). CONCLUSIONS: Noninvasive TEA improves gastric accommodation and dyspeptic symptoms, possibly by downregulating the IL-6 expression in duodenal bulb mucosa via the vagal efferent pathway.

The treatment effects of Trametes Robiniophila Murr against colorectal cancer: A mini-review.

Colorectal cancer (CRC) is a worldwide disease threatening people's lives. Surgery and chemotherapy are still the main methods for CRC treatment. However, the side effects and chemotherapeutic drug resistance restrict the application of chemotherapy. Trametes Robiniophila Murr, also known as Huaier, is a traditional Chinese medicine that has been used for more than 1,600 years. Huaier extracts have promising anti-cancer effects on hepatoma, breast cancer, and gastric cancer. Nowadays, the tumor inhibition of Huaier on CRC has attracted more and more attention. This review mainly provides the possible anti-tumor mechanisms of Huaier for CRC treatment in apoptosis and inhibiting proliferation of tumor cells, preventing epithelial-mesenchymal transformation (EMT), weakening proliferation and differentiation of CRC stem cells, decreasing the vessel density in tumor tissues, and enhancing the immune system and chemotherapeutic efficacy. Huaier extract may be a good candidate for CRC treatment, especially when combined with other chemotherapeutic agents.

Regulation of Janus Kinase-signal Transducers and Activators of Transcription Pathways in Psoriatic Mice by Chinese Herbal Compound and Efficacy of Chinese Traditional Medicine under Nano-suspension Technology.

The mechanism of the treatment of psoriasis-like mice with the Chinese herbal compound YinXie No.1 prepared by nano-suspension technology was investigated based on Janus kinase-signal transducers and activators of transcription (JAKs/STATs) pathway. The high-pressure homogenization technology was used in the preparation of the YinXie No.1 nano-suspensions. Then, 50 Kunming mice were equally classified into the negative control group (NC), the psoriasis model group (PsM) prepared with 5% imiquimod cream on the back, the Tripterygium glycosides-gavage group (TrG), the YinXie No.1-gavage group (YX1), and the YinXie No.1 nano suspension group (Nano-YX1). The pathological changes and the differential expressions of STAT3 and STAT5 were compared in each group after the treatment. The results showed that the particle size of nano-suspension powder was smaller and had strong stability compared with the active pharmaceutical ingredient (API). Compared with the NC group, psoriasis-like lesions were observed in the PsM group. Compared with the PsM group, the conditions of the erythema on skin lesions, the mRNA expression of STAT3 and STAT5, and protein expression of p-STAT3 and p-STAT5 in the TrG group, YX1 group, and Nano-YX1 group were notably decreased (P<0.05). Compared with the TrG group and YX1 group, the improvement effect of various indexes in the Nano-YX1 group was closer to that in the NC group, but there were differences between the NC group (P<0.05). Chinese herbal compound was helpful to regulate and control the JAKs/STATs pathway to improve the symptoms of psoriasis mice, and the preparation of Chinese herbal compound decoction by nano-suspension technology could improve the therapeutic effect.

Sub-chronic and developmental toxicity of transdermal delivery of Renzhu ointment in young SD rats.

Purpose: Renzhu ointment (Renzhuqigao, RZQG) is a patented herbal drug derived from Chinese traditional medicine formula and modern clinical experience for the transdermal treatment of non-infectious infantile diarrhoea. The safety of RZQG in preclinical studies has not been reported.Materials and methods: In this study, the pups of parent rats were examined for sub-chronic toxicity and developmental toxicity. After 21 days of birth, they were exposed to RZQG through their abdominal skin at doses of 0.1, 0.3, and 0.9 g/kg/day for 4 weeks and then were observed for another four weeks during their recovery period.Results: During the administration period, RZQG had no significant toxicological effect on body weight, food consumption, external eye examination, urinalysis, bone marrow examination, histopathology, central nervous system, reproductive system, or skeletal development. However, in the 0.9 g/kg/day group, the skin of some rats became dry and cracked, red and swollen, forming a white scab, while the white blood cells (WBC) count in female rats was lower and cholesterol (CHOL), triglycerides (TG), and glutamyl-transferase (GGT) were higher (p < 0.05).Conclusions: Rats receiving 0.9 g/kg/day exhibited skin irritation and were suspected to have a mild liver injury. There was no evidence of delayed toxicity four weeks after withdrawal. Therefore, the no-observed adverse effect level of RZQG was 0.3 g/kg/day (30 times the clinical dose planned and 4.92 times the human equivalent dose).

Perspectives of East Asian patients and physicians on complementary and alternative medicine use for inflammatory bowel disease: results of a cross-sectional, multinational study.

BACKGROUND/AIMS: Complementary and alternative medicine (CAM) is prevalent in East Asia. However, information on CAM in East Asian patients with inflammatory bowel disease (IBD) is scarce. We aimed to profile the prevalence and pattern of CAM use among East Asian IBD patients and to identify factors associated with CAM use. We also compared physicians' perspectives on CAM. METHODS: Patients with IBD from China, Japan, and South Korea were invited to complete questionnaires on CAM use. Patient demographic and clinical data were collected. Logistic regression analysis was applied for predictors of CAM use. Physicians from each country were asked about their opinion on CAM services or products. RESULTS: Overall, 905 patients with IBD participated in this study (China 232, Japan 255, and South Korea 418). Approximately 8.6% of patients with IBD used CAM services for their disease, while 29.7% of patients sought at least 1 kind of CAM product. Current active disease and Chinese or South Korean nationality over Japanese were independent predictors of CAM use. Chinese doctors were more likely to consider CAM helpful for patients with IBD than were Japanese and South Korean doctors. CONCLUSIONS: In 8.6% and 29.7% of East Asian patients with IBD used CAM services and products, respectively, which does not differ from the prevalence in their Western counterparts. There is a significant gap regarding CAM usage among different Asian countries, not only from the patients' perspective but also from the physicians' point of view.

[Electroacupuncture of "Shangjuxu"(ST37) and "Tianshu"(ST25) reduces colonic injury by suppressing NF-κB/NLRP3 signaling in rats with ulcerative colitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Shangjuxu"(ST37) and "Tianshu"(ST25) on colonic mucosal injury and activities of nuclear factor-κB (NF-κB)/Nod-like receptor family，pyrin domain-containing 3 (NLRP3) inflammasome signaling in the colonic tissue in rats with ulcerative colitis (UC), so as to explore its mechanisms underlying improvement of UC. METHODS: Male SD rats were randomly divided into blank, model, medication and EA groups, with 12 rats in each group. The UC model was established by enema of 2-4-6 trinitrobenzene sulfonic acid +50% ethanol (2.5 mL). EA (10 Hz/50 Hz) was applied to bilateral ST37 and ST25 for 20 min, once a day, for a total of 10 days. Rats of the medication group received gavage of mesalazine suspension (2 mL：0.2 g/kg+0.9% saline) once a day, for 10 days. The rats' general conditions were recorded for calculating the disease activity index (DAI) score (0-4 points). The colonic tissue was sampled for giving colonic mucosa damage index (CMDI, 0-5 points) score and for observing histopathological changes after hematoxylin-eosin (HE) staining, and for detecting expression levels of NF-κB and NLRP3 by using immunohistochemistry and Western blot, separately. The contents of serum interleukin-1ß (IL-1ß), NLRP3 and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. RESULTS: Compared with the blank group, the DAI and CMDI scores, contents of serum IL-1ß, NLRP3, and TNF-α, as well as the immunoactivity and expression of NF-κB and NLRP3 proteins were significantly increased in the model group (P<0.05). Relevant to the model group, modeling-induced increases of DAI and CMDI scores, serum IL-1ß, NLRP3 and TNF-α contents, and NF-κB and NLRP3 expression were reversed in both medication and EA groups (P<0.05), the effect of EA was apparently superior to that of mesalazine in down-regulating CMDI score and serum IL-1ß level (P<0.05). No significant diffe-rences were found between the medication and EA groups in down-regulating DAI score, serum TNF-α and NLRP3 contents, and expression of NF-κB and NLRP3 proteins (P>0.05). The rats' general conditions including arch back sloth, anorexia, loss of fur gloss, weight loss, lethargy and loose of stool, and histopathological changes such as necrosis of intestinal mucosa, formation of obvious ulcerative surface, with many neutrophils and pus cells and inflammatory cell infiltration were obvious in the model group, which were relative milder in both medication and EA groups. CONCLUSION: EA can relieve colonic injury in UC rats, which may be related to its functions in down-regulating serum IL-1ß, TNF-α and NLRP3 levels by suppressing colonic NF-κB / NLRP3 inflammasome signaling.

Evidence for Anticancer Effects of Chinese Medicine Monomers on Colorectal Cancer.

Colorectal cancer is one of the most commonly occurring cancers worldwide. Although clinical reports have indicated the anticancer effects of Chinese herbal medicine, the multiple underlying molecular and biochemical mechanisms of action remain to be fully characterized. Chinese medicine (CM) monomers, which are the active components of CM, serve as the material basis of the functional mechanisms of CM. The aim of this review is to summarize the current experimental evidence from in vitro, in vivo, and clinical studies for the effects of CM monomers in colorectal cancer prevention and treatment, providing some useful references for future research.

Temporal Changes in the Treatment Paradigm and Long-term Prognosis of Patients With Crohn's Disease: A Hospital-Based Cohort Study in China.

BACKGROUND: The temporal trends in medical treatment and long-term outcomes of patients with Crohn's disease (CD) have not been well elucidated in China over the past 2 decades. Accordingly, we aimed to evaluate the treatment paradigm and long-term clinical course of Chinese patients with CD in a hospital-based cohort. METHODS: All adult patients newly diagnosed with CD (n = 1338) between 1999 and 2019 in the Sir Run Run Shaw Hospital were included in this cohort. Medication utilization, disease outcomes, and risk factors were investigated. RESULTS: Overall, 48.7%, 35.6%, 67.8%, and 61.6% of patients used 5-aminosalicylates (5-ASA), corticosteroids, thiopurines, and infliximab (IFX), respectively. The cumulative risk of 5-ASA and corticosteroid initiation decreased during follow-up, whereas that of IFX initiation increased. Throughout a median follow-up duration of 26.4 (interquartile range, 12.0-49.2) months, a total of 486 and 300 patients underwent hospitalization and surgery, respectively. Of the 1097 patients with B1/B2 disease behavior at diagnosis, 10.3% experienced phenotype progression. The hospitalization rate decreased after 2015; however, surgery and phenotype progression rates did not significantly change. A Cox regression analysis indicated that IFX use since diagnosis was a contributing factor for lower rates of hospitalization and phenotype progression, whereas thiopurine use was associated with a lower surgery rate. CONCLUSIONS: Infliximab use was observed to increase as 5-ASA and corticosteroid use decreased. Additionally, hospitalization rates decreased following temporal changes in IFX management, yet the surgery and phenotype progression rates remained the same.

[Rapid chemome profiling of Cistanche salsa using DI-MS/MS~(ALL)].

The current study aims to rapidly and comprehensively profile the chemical composition of Cistanche salsa using direct infusion coupled with MS/MS~(ALL)(DI-MS/MS~(ALL)). The C. salsa extract was directly imported into electrospray ionization(ESI) source of quadrupole time-of-flight(Q-TOF) mass spectrometer with an infusion pump at a flow rate of 10 µL·min~(-1). Acquisition program was applied under negative ionization polarity to collect one MS~1 spectrum(m/z 50-1 200), followed by 1 150 MS~2 spectra with precursor isolation window(m/z 1) amongst mass range m/z 50-1 200. After each MS~2 spectrum was matched to its precursor ion, putative identification was conducted through matching mass spectral data with literature and database. A total of 31 components were identified from C. salsa, including 9 phenylethanoid glycosides, 2 iridoids, 4 saccharides, 9 organic acids, and 7 other compounds, similar to those from C. tubulosa and C. deserticola. In conclusion, DI-MS/MS~(ALL), a facile and reliable analytical tool, can be employed for qualitative analysis of chemical constituents in C. salsa. The research offers a promising strategy to achieve rapid chemome profiling of herbal medicine and provides an alternative source of Cistanches Herba.

Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease.

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.

[Myofascial trigger point: an indicator of acupoint sensitization].

OBJECTIVE: The present study is to investigate the characteristic distribution of primary pain points and referred pain areas in patients with knee-joint pain diseases, therefore revealing the correlation between the myofascial trigger point and acupoint sensitization. METHODS: A total of 483 patients (320 men and 163 women, 36 to 72 years in age) with knee-joint pain recruited from 4 clinical centers were observed from July, 2017 to April, 2019 in the present study. The areas of primary and referred pain in these patients were detected by thumb-pressing and marked on human anatomic atlas. RESULTS: Of the 483 enrolled participants, 336 had lesion sites or tender points around the injured knee joint, and 147 with myofascial pain syndrome showed referred pain spots (zones) in the knee joint area. In 105 patients with patellar tendonitis, epiphysitis of the tibial tubero-sity, or quadriceps tendonitis, the pain area was mainly distributed in the anterior region of the knee. In 76 patients with medial collateral ligament injury, medial meniscal lesion, goose foot bursitis or semimembranosus ending-point inflammation, the pain points mainly occurred in the medial area of the knee. In 127 patients with lateral collateral ligament, lateral meniscus lesion, iliotibial band tendonitis, popliteus or triceps tendinitis, the pain spots were found in the lateral region of the knee. In 28 patients with posterior cruciate ligament injury or popliteal fossa tendonitis, the local pain was found to be at the back of the knee. Referred pain areas were normally detected in the lateral femoral muscles (43 cases), anterior femoral muscles (39 cases), adductor group of femur (26 cases), posterior popliteal fossa muscles group (15 cases), hamstrings (13 cases) and medial leg (11 cases)．. CONCLUSION: The primary pain areas or spots of the knee injury mainly distribute around the joint, whereas those of each muscle group lesion are often located in their respective skeletal muscle. Most of the referred pain areas often occur in the distal end of skeletal muscle and around the knee joint. Primary myofascial trigger points may be considered to be an indicator of acupoint sensitization.

[Clinical observation on the distribution characteristics and rules of pressing sensitive acupoints in bronchial asthma patients].

OBJECTIVE: To compare the distribution characteristics of pressing sensitive acupoints on the body surface between bronchial asthma (BA) patients and healthy subjects, and to analyze the distribution rules of pressing sensitive acupoints in BA patients. METHODS: Seventy BA patients and 70 healthy subjects were selected in this study. The pressing sensitive acupoints were checked with finger pulp and marked on human nerve segment graph. The numbers of pressing sensitive acupoints were counted and the positional relationship between distribution of pressing sensitive acupoints and the position of meridians and nerve segment was observed. RESULTS: (1) The incidence rates of pressing sensitive acupoints in BA patients group and healthy subjects group were 91.4% (64/70) and 15.7% (11/70) respectively, and the BA patients group was higher than the healthy subjects group (P<0.01). (2) The top 3 meridians with pressing sensitive acupoints occuring in BA patients were bladder meridian of foot-taiyang, lung meridian of hand-taiyin and large intestine meridian of hand-yangming, and the most frequent pressing sensitive acupoints were Feishu（BL 13）, Xinshu（BL 15）, Chize（LU 5） and Jueyinshu (BL 14). (3) The pressing sensitive acupoints in BA patients were distributed mainly on C4, C6 and T1-T6 nerve segment. CONCLUSION: Pressing sensitive acupoints have a close correlation with physical condition, and there is a close relation between pressing sensitive acupoints distribution and corresponding meridians and nerve segments in BA patients.

[Correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases].

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (n=143), ulcerative colitis (n=108), chronic appendicitis (n=87) and other intestinal diseases (n=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (n=8), in which the enteritis model were established, and a control group (n=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (P<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T12 to L2. CONCLUSION: Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.