Lactic acid bacteria(LAB) have biological functions such as nutrition,bacteriostasis and immune regulation,which play important roles in the fields of food,agriculture and animal husbandry,industry,medicine and so on. At present,in the clinical application research of LAB,the focus of attention is on gastrointestinal diseases,urinary tract infections,allergic rhinitis,anti-tumor,etc.,but there are few introductions to the research progress of LAB in ocular application. In addition to regulating inflammation,the mechanism of action of lactic acid bacteria in the treatment of eye diseases is also affected by different mechanisms,which can be divided into direct and indirect effects. This article reviews the application of lactic acid bacteria in ocular surface diseases,fungal keratitis,lens and retinal diseases,summarizes and summarizes lactic acid strains and their related mechanisms,compares the differences of different lactic acid strains in the treatment of ophthalmic diseases. The in vitro,in vivo and clinical evidence of lactic acid bacteria in ophthalmic research are summarized,and the use of lactic acid bacteria in the treatment has high safety. The application of ophthalmic diseases has shown significant innovation and clinical significance,broadened the application scope of lactic acid bacteria in ophthalmology,and provided new ideas for future clinical treatment.

Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Objective:To discuss the effects of 5-aza-2'-deoxycytidine(5-Aza-CdR)on autophagy and apoptosis of the TPC-1 cells in subcutaneous xenograft tumor tissue of the nude mice,and to clarify its mechanism.Methods:Sixteen female BALB/c nude mice were inoculated with human papillary thyroid carcinoma(PTC)TPC-1 cells in the right axilla to establish the xenograft tumor model.After tumor formation,the mice were randomly divided into control group and experiment group(n=8).The nude mice in control group were given an intraperitoneal injection of saline,while the nude mice in experiment group were given the intraperitoneal injection of 5-Aza-CdR,administered once every other day for four weeks.The growth status of xenograft tumor of the mice in both groups was observed,and the mice were sacrificed after the final administration and the tumor weights of the nude mice in two groups were detected.HE staining was used to observe the pathomorphology of xenograft tumor tissue of the nude mice in both groups;immunohistochemistry was used to detect the expression levels of microtubule-associated protein light chain 3(LC3),B-cell lymphoma 2(Bcl-2),and Bcl-2-associated X protein(Bax)in xenograft tumor tissue of the nude mice in two groups;real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of LC3,Beclin-1,Bcl-2,Bax,mitogen-activated protein kinase kinase(MEK),extracellular signal-regulated kinase 1(ERK1),extracellular signal-regulated kinase 2(ERK2),phosphorylated EPK1(p-ERK1),and phosphorylated EPK2(p-ERK2)mRNA and proteins in xenograft tumor tissue of the nude mice in two groups.Results:Compared with control group,the tumor volume and weight of the nude mice in experiment group were significantly decreased(P＜0.01).The number of cancer cells of the nude mice in control group was high,and the cells were densely arranged,with irregular shapes,clear nuclear staining,large overlapping nuclei,and lobulation,showing significant pathological mitotic figures consistent with PTC pathological characteristics.The number of cancer cells of the nude mice in experiment group showed a significant decresing trend,and the cells were sparse arrangement,nuclear shrinkage,and less distinct nuclei,with a significant increase in connective tissue.Compared with control group,the expression levels of LC3B and Beclin-1 mRNA and proteins in xenograft tumor tissue of the nude mice in experiment group were significantly increased(P＜0.05)and the ratio of and Bax/Bcl-2 was increased(P＜0.05 or P＜0.01),while the expression levels of MEK,ERK1/2,and p-ERK1/2 mRNA and proteins were significantly decreased(P＜0.05 or P＜0.01).Conclusion:5-Aza-CdR can inhibit the growth of TPC-1 cells in subcutaneous xenograft tumor tissue of the nude mice,induce the autophagy,and promote the apoptosis of the tumor cells.The mechanism may be related to the inhibition of the mitogen-activated protein kinase(MAPK)/MEK/extracellular signal-regulated kinase(ERK)signaling pathways.

Objective:To conduct scoping review of researches on application of traditional Chinese medicine exercises in exercise rehabilitation of patients with heart failure, so as to provide reference for effective clinical intervention of traditional Chinese medicine exercises.Methods:Chinese and English literature published in PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, Wanfang Database and China Biology Medicine disc were searched by computer, and the search deadline was from database establishment to May 28, 2023. The Joanna Briggs Institute Scoping Review Guide was used as a methodological framework to summarize and analyze the included literature.Results:A total of 19 literatures were included, including 17 randomized controlled trials and 2 quasi-randomized controlled trials. The subjects of the intervention were heart failure patients with New York Heart Association heart function gradeⅠ toⅢ. The types of exercises mainly included Eight Pieces of Brocade and Tai Chi. The intervention duration was mostly 30 min each time, and the frequency was mostly 3 to 5 times a week. The intervention intensity was mostly based on The Borg Rating of Perceived Exertion (RPE), and the intervention duration was mostly 3 months. Most of the implementation scenarios were "hospital-home" or home. Traditional Chinese medicine exercises had a positive effect on the clinical symptoms, psychological state and quality of life of patients with heart failure, and were safe and feasible.Conclusions:Traditional Chinese medicine exercises have a positive effect on the exercise rehabilitation of patients with heart failure, and are safe and feasible.

Sarcopenia is an age-related syndrome with progressive, generalized loss of muscle mass, strength, and physiological function. Low muscle mass is an important diagnostic criterion for sarcopenia. Ultrasound is safe, convenient and cost-effective, with extensive availability. It's a promising diagnostic tool for muscle mass assessment and sarcopenia screening in the elderly population. This review focuses on the specific methods and latest research progress on ultrasound assessment of sarcopenia.

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

Objective:To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years.Methods:In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed.Results:The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment.Conclusion:A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective: To discuss the misdiagnosis of pyriform sinus fistula and to better understand this kind of illness. Methods: The analysis was based on twenty-eight patients with congenital pyriform sinus fistula aged from 11 months to 14 years, with the median age of 5 years, and who were surgically treated from January 2013 to January 2017 in Kunming Children′s Hospital.Twenty patients were misdiagnosed in other hospital.After the routine examination of neck ultrasound and enhanced CT, internal fistula was found by self-retaining laryngoscope, traced by methylene blue, and excised by high ligation. Results: Twenty patients were misdiagnosed.The misdiagnosis time ranged from 6 months to 3 years.Under self-retaining laryngoscope, piriform fossa fistula were found in all patients.Nineteen fistula were found in the left and 1 in the right.The fistula in patients was unilateral.Seven cases were misdiagnosed as suppurative lymphadensitis, undergone abscess incisional drainage many times.Three cases were misdiagnosed as thyroglossal duct cyst and performed excision of thyroglossal duct cyst.One case was treated by extended Sistruck operation again because the doctor considered that excision of middle segment of hyoid bone was not enough and the fistula was not ligated completely.One case was misdiagnosed as second branchial cleft fistula on the right side of the neck.Nine cases were misdiagnosed as hyroid-associated diseases including 2 cases suppurative thyroiditis, 2 cases subacute thyroiditis and 5 cases thyroid neoplasms.Among them, 2 cases underwent partial thyroidectomy.All the patients were treated with high ligation of fistula under general anesthesia.The operation was smooth, and no hoarseness, bucking and pharyngeal fistula occurred after the operation.Postoperative follow-up time ranged from 12 months to 4 years and the median follow-up was 18 months without recurrence.The diagnosis was confirmed pathologically. Conclusions Pyriform sinus fistula in children was uncommon and easily misdiagnosed in clinic.The majority of physician including some otolaryngologists were lack of understanding of the disease.It should be regarded as one of the important differential diagnosis of neck mass in children.Children with recurrent left neck infection and/or abscess should be highly suspected.Self-retaining laryngoscopic examination can make a definite diagnosis and high ligation of the fistula through the external neck approach can achieve good therapeutic effect.