Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.

Ulcerative colitis （UC） is a chronic inflammatory bowel disease with complex etiology. The pathogenesis of this disease， due to a combination of factors， is complex and has not yet been elucidated. Among them， intestinal mucosal barrier damage is the basic pathological change of UC. As a non-destructive response of cells， autophagy regulates intestinal mucosal immunity， inflammation， oxidative stress， and bacterial homeostasis through degradation and reabsorption to actively repair damaged intestinal mucosal barrier， exerting a key role in the occurrence and development of UC. The disease is mainly treated clinically with aminosalicylic acid preparations， glucocorticoids， and immunosuppressants. Western medicine treatment of the disease has a fast onset of effect， and the short-term efficacy is definite， but the long-term application is easy to be accompanied by more adverse reactions. Moreover， some drugs are expensive， bringing great physical and mental pain and economic burden to patients. Therefore， it is urgent to explore new therapies with stable efficacy and mild adverse effects. In recent years， a large number of studies have shown that Chinese medicine can regulate autophagy of the intestinal mucosa with multiple targets and effects and repair the intestinal mucosal barrier function， thereby inhibiting the development of UC. Many experiments have shown that the active ingredient or monomers and compound formulas of Chinese medicine can improve the immunity of the intestinal mucosa， inflammation， oxidative stress， and flora by regulating the level of autophagy to maintain the normal function of the intestinal mucosal barrier to effectively intervene in UC， providing a new measure for the prevention and treatment of UC. However， there is a lack of systematic review of Chinese medicine in regulating the level of autophagy in the intestinal mucosa for the prevention and treatment of UC. Therefore， based on the current research on UC， autophagy process， and Chinese medicine treatment， this article reviewed the relationship of autophagy and its key target proteins with UC to clarify the key role of autophagy in UC production and systematically summarized Chinese medicines targeting the regulation of autophagy to treat UC in recent years to provide new ideas for the treatment and drug development of UC.

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) genotype of Yersinia pestis and its regional distribution characteristics in natural plague focus of Tibet Autonomous Region. Methods:A total of 125 representative Yersinia pestis strains isolated from natural plague focus in Tibet Autonomous Region at different times, regions, hosts and vectors were selected as experimental strains, and the phenol chloroform mixed extraction method was used to extract Yersinia pestis DNA. Three pairs of CRISPR primers (for YPa, YPb, YPc locus) were used to amplify the DNA of the experimental strains, and the CRISPR genotype of Yersinia pestis was determined by sequencing. Results:All 125 strains of Yersinia pestis had three CRISPR locus: YPa, YPb, and YPc. A total of 18 spacer were found, including 8 in YPa loci, 6 in YPb loci, and 4 in YPc loci. Two new types of spacers had been discovered, namely b52 and c14. CRISPR typing revealed 10 genotypes, including G1, G7, G7-b4''', G7-b52, G7-c2 -, G8, G22, G22-a4 -, G22-b4''', and G22-c14, of which 6 were newly discovered genotypes. Among the 125 experimental strains, G7 was the main genotype, accounting for 65.6% (82/125), which was distributed in 6 prefecture level citys and 1 region of Tibet Autonomous Region. Next were G22 and G7-c2 - genetypes, accounting for 14.4% (18/125) and 11.2% (14/125), respectively. G22 gene type was distributed in Nagqu, Changdu, Lhasa citys, and Ngari Prefecture, while G7-c2 - genetype was distributed in Shigatse and Shannan cities. Conclusion:The CRISPR locus of Yersinia pestis in natural plague focus of Tibet Autonomous Region is highly polymorphic, and the Yersinia pestis strains with different genotypes have obvious regional distribution characteristics.

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

Objective:To evaluate the clinical efficacy and safety of hematoporphyrin monomethyl ether (HMME) -mediated photodynamic therapy (PDT) in the treatment of facial port-wine stains (PWS) in children with Sturge-Weber syndrome (SWS) .Methods:A retrospective analysis was conducted based on the clinical data from SWS children treated with HMME-PDT at the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from December 2020 to January 2022. HMME was intravenously injected at a dose of 5 mg/kg, followed by the irradiation of SWS lesions with a 532-nm light-emitting diode light source, and the treatment interval was 8 weeks. The efficacy of HMME-PDT for SWS was evaluated based on the subsidence of erythema and changes in the number and density of blood vessels under a dermoscope before and after treatment; adverse events after treatment were recorded. Fisher's exact test was used to analyze differences in efficacy.Results:A total of 15 children with SWS were included, comprising 7 males and 8 females, with an average age of 4.74 years (range, 1 - 14 years). There were 10 cases of clinical phenotype Ⅰ and 5 cases of type Ⅱ; 10 patients were accompanied by glaucoma, 6 by epilepsy, and 10 showed abnormalities on craniocerebral imaging. After HMME-PDT treatment, 4 out of 15 patients achieved complete remission of SWS lesions, 3 showed marked improvement, and 5 achieved improvement. Among 8 cases receiving 2 sessions of treatment, 1 achieved marked improvement and 4 showed improvement; among 7 cases receiving 3 or more sessions of treatment, 4 achieved complete remission, 2 achieved marked improvement, and 1 showed improvement; the proportions of patients achieving complete remission and marked improvement were significantly higher among those receiving 3 or more sessions of treatment than those receiving 2 sessions (both P < 0.05). Among 7 patients with pink-type PWS, 1 recovered completely, 2 achieved marked improvement, and 4 showed improvement; among 4 patients with purplish-red-type PWS, 3 recovered completely and 1 showed marked improvement; among 4 patients with thickened-type PWS, 1 achieved improvement; there was a significant difference in the proportions of patients achieving marked improvement or improvement among the patients with different types of PWS (both P < 0.05). Among 14 patients with lesions involving the central face region, 4 achieved marked improvement and 2 showed improvement; among 15 with lesions involving the lateral face region, 5 recovered completely, 3 achieved marked improvement, and 4 showed improvement; the recovery rate of lesions was higher in the lateral face region than in the central face region ( P < 0.05). Under a dermoscope, the skin lesions showed 4 vascular patterns: short rod-shaped vessels in 3 cases, linear vessels in 4, reticular vessels in 5, and mixed-type vessels in 3. The 3 patients with short rod-shaped vessels all recovered completely; among the 4 patients with linear vessels, 2 achieved marked improvement, and 2 showed improvement; among the 5 patients with reticular vessels, 1 recovered completely, 1 achieved marked improvement, and 3 showed improvement; the 3 patients with mixed-type vessels all showed poor response to the treatment; the proportions of patients who recovered completely and those who achieved improvement significantly differed among the patients with 4 different vascular patterns (both P < 0.05). All the children experienced varying degrees of pain, swelling, purpura, and crusting after treatment, but none exhibited exacerbation of ocular or neurological complications. Conclusion:HMME-PDT was safe and effective in the treatment of PWS in children with SWS, and its efficacy was related to the number of treatment sessions, lesion types and locations.

Ulcerative colitis （UC） mainly occurs in the colon and rectum， with complex pathological mechanism. The occurrence of ulcerative colitis is associated with the uncontrollable inflammatory response of the intestine. The Western medicine therapy of UC mainly uses glucocorticoids and immunosuppressants to reduce intestinal inflammation. While blocking the progress of UC to a certain extent， it causes severe adverse reactions. More and more studies have confirmed that traditional Chinese medicine （TCM） has obvious advantages in the prevention and treatment of UC and can significantly reduce the recurrence of the disease. Pyroptosis， a novel form of cell death， can destroy cell structure， release intracellular pro-inflammatory substances， and mediate intestinal immune response in UC. TCM can promote pyroptosis （removing excess） or inhibit pyroptosis （replenishing deficiency）， which is consistent with the regulation of Yin and Yang. TCM plays a role in the treatment of UC mainly by inhibiting pyroptosis （replenishing deficiency） and reducing intestinal immune response. In recent years， a large number of studies have been carried out to decipher the mechanism of TCM in the treatment of UC via NOD-like receptor protein domain 3 （NLRP3）-mediated pyroptosis pathway. The results have demonstrated that NLRP3 pathway is the key target of TCM in the treatment of UC. However， a comprehensive summary remains to be carried out on the inhibition of NLRP3-mediated pyroptosis pathway by TCM in the treatment of UC. Therefore， we retrieved the articles in this field in recent years with the keywords "pyroptosis"， "NLRP3"， "ulcerative colitis"， and "Chinese medicine". The Chinese medicines regulating NLRP3 pathway mainly have the functions of clearing heat and drying dampness， harmonizing Qi and blood， moving Qi and dredging fu-organs， and invigorating spleen and removing dampness. The findings can help researchers to fully understand the mechanism of TCM in the treatment of UC via the NLRP3 pathway and provide a theoretical basis for the treatment of UC and further drug development.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.
Humans ; Cardiomyopathy, Dilated/genetics* ; Genetic Testing ; Genetic Counseling ; Computational Biology ; Frameshift Mutation ; Mutation ; Filamins

Ulcerative colitis （UC） is a disease that affects the mucosal and submucosal layers of the colon and is characterized by inflammation of the intestinal mucosa. The incidence of UC is increasing year by year， and it is complex and refractory， severely impacting the physical and mental health of patients. The pathological mechanism of this disease is complex， with immune responses and uncontrollable inflammatory reactions in the intestine being important physiopathologic mechanisms. Toll-like receptor 4 （TLR4）， as a transmembrane signaling receptor， plays a key role in mediating immune responses and inflammatory reactions in the development of UC. Currently， the treatment of UC mainly relies on salicylic acids， glucocorticoids， and other agents to reduce intestinal inflammation. While these drugs can partially inhibit the progression of the disease， they often come with significant adverse effects and the potential for relapse upon discontinuation. Traditional Chinese medicine （TCM） offers multiple pathways， effects， and targets for regulating the TLR4 pathway， suppressing inflammatory responses， and effectively intervening in the progression of UC. This approach has become a hot topic in the prevention and treatment of UC. Numerous studies have shown that TCM treatment of UC has unique advantages. TCM can enhance immune defenses， suppress inflammatory responses， promote intestinal mucosal healing， and maintain the balance of the intestinal microbiota by regulating the TLR4 signaling pathway， thereby effectively treating UC， with substantial progress achieved. However， there is currently a lack of comprehensive reviews on the role of TCM in regulating the TLR4 signaling pathway for the treatment of UC. Therefore， this article systematically summarized the relationship between the TLR4 signaling pathway and UC， as well as the role of TCM in this context， by reviewing relevant literature from recent years， aiming to provide new insights into the potential treatment and new drug development for UC.

Ulcerative colitis （UC） is a clinical chronic intestinal disease， and the damage of the intestinal epithelial mucus barrier is an important pathological mechanism of UC. Mucin 2 （MUC2） is a major component of the intestinal mucus barrier， and goblet cells are the “main force” of MUC2 secretion， maintaining and renewing the intestinal mucus layer to ensure its integrity. Therefore， repairing the intestinal mucus barrier by promoting the synthesis of MUC2 by goblet cells is an important strategy for the treatment of UC. Traditional Chinese medicine scholars believe that there is an inherent layer of “lipid membrane” or “fat paste” in the intestine， and pathological factors such as moisture and heat lead to the thinning of this structure， which is the fundamental pathogenesis of “diarrhea” and “intestinal dysentery”. It coincides with the damage of intestinal mucus barrier leading to UC in modern medicine. Based on this， this paper summarized the mechanism of Chinese herbal compounds or Chinese herbal active components in regulating intestinal mucus barrier to interfere with UC. It was found that Chinese herbal compounds such as Huanglian jiedu decoction， Shaoyao decoction and Compound Kusen decoction， as well as Chinese herbal active ingredients such as volatile oil of Atractylodes lancea， paeoniflorin and papaya triterpenes could promote the synthesis and secretion function of goblet cells， and achieve the purpose of “thickening intestine”， thus relieving UC symptoms.