AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To evaluate strategies for screening and diagnosing Lynch syndrome associated endom-etrial carcinoma(LS-EC)in clinical practice and analyze clinicopathological characteristics of LS-EC.Methods:A total of 258 patients with endometrial carcinoma who underwent surgery in The Fourth Hospital of Hebei Medical University from January 2019 to January 2022 were included.All enrolled patients underwent postoperative immu-nohistochemical testing for mismatch repair(MMR)proteins.Based on the expression status of the four MMR proteins,the patients were divided into deficient mismatch repair(d-MMR)group(57 cases)and proficient mis-match repair(p-MMR)group(201 cases).Among them,23 patients in the d-MMR group underwent germline gene testing for Lynch syndrome(LS).According to germline gene testing results,these patients were further classified into LS-EC(n=8)and non-LS-EC(n=15)groups.Clinicopathological features of LS-EC patients were analyzed.Results:Among the 258 endometrial carcinoma patients,57cases(22.1%)exhibited d-MMR,with MLH1 and PMS2 co-deletion being the most common(61.4%,35/57).Among the23 d-MMR patients who under-went genetic testing,8 cases(34.8%)were identified as having LS-EC,including 5 cases(62.5%)of MLH1 gene mutation,1 case(12.5%)of MSH2 gene mutation,1 case(12.5%)of PMS2 gene mutation and 1 case(12.5%)of MSH6 gene mutation.Compared with the non-LS-EC group,the LS-EC patients showed significant familial aggregation and higher pathological grade(P<0.05).Conclusions:Immunohistochemical analysis of MMR proteins combined with family history represents an effective screening strategy for LS-EC,however defini-tive diagnosis requires germline genetic testing.Among LS-EC cases,MLH1 is the most frequently mutated gene.LS-EC patients are characterized by familial clustering and high pathological grade.Discrepancies between immu-nohistochistochemistry and genetic testing results present challenges in the definitive diagnosis of LS-EC.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

The clinical manifestations of ovarian cancer are occult, often diagnosed as late stage, often accompanied by peritoneal metastasis, and easy to relapse after surgery. Compared with traditional tumor treatment methods, photodynamic therapy (PDT) is a minimally invasive and tumor-targeting specific treatment method, which can not only produce photochemical reactions to destroy tumor cells and trigger immune responses, but also use its fluorescence to support photodynamic diagnosis and fluorescence-guided surgery. Clinical studies have shown that photodynamic diagnosis and photodynamic fluorescence-guided tumor cell reduction, PDT and its combination therapy have great therapeutic potential, and have been recognized and gradually applied in recent years. This article reviews the current status of PDT in the treatment of advanced ovarian cancer, and discusses its possible application prospects in order to provide a safe and effective treatment for the comprehensive treatment of clinical ovarian cancer.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To evaluate strategies for screening and diagnosing Lynch syndrome associated endom-etrial carcinoma(LS-EC)in clinical practice and analyze clinicopathological characteristics of LS-EC.Methods:A total of 258 patients with endometrial carcinoma who underwent surgery in The Fourth Hospital of Hebei Medical University from January 2019 to January 2022 were included.All enrolled patients underwent postoperative immu-nohistochemical testing for mismatch repair(MMR)proteins.Based on the expression status of the four MMR proteins,the patients were divided into deficient mismatch repair(d-MMR)group(57 cases)and proficient mis-match repair(p-MMR)group(201 cases).Among them,23 patients in the d-MMR group underwent germline gene testing for Lynch syndrome(LS).According to germline gene testing results,these patients were further classified into LS-EC(n=8)and non-LS-EC(n=15)groups.Clinicopathological features of LS-EC patients were analyzed.Results:Among the 258 endometrial carcinoma patients,57cases(22.1%)exhibited d-MMR,with MLH1 and PMS2 co-deletion being the most common(61.4%,35/57).Among the23 d-MMR patients who under-went genetic testing,8 cases(34.8%)were identified as having LS-EC,including 5 cases(62.5%)of MLH1 gene mutation,1 case(12.5%)of MSH2 gene mutation,1 case(12.5%)of PMS2 gene mutation and 1 case(12.5%)of MSH6 gene mutation.Compared with the non-LS-EC group,the LS-EC patients showed significant familial aggregation and higher pathological grade(P<0.05).Conclusions:Immunohistochemical analysis of MMR proteins combined with family history represents an effective screening strategy for LS-EC,however defini-tive diagnosis requires germline genetic testing.Among LS-EC cases,MLH1 is the most frequently mutated gene.LS-EC patients are characterized by familial clustering and high pathological grade.Discrepancies between immu-nohistochistochemistry and genetic testing results present challenges in the definitive diagnosis of LS-EC.

The clinical manifestations of ovarian cancer are occult, often diagnosed as late stage, often accompanied by peritoneal metastasis, and easy to relapse after surgery. Compared with traditional tumor treatment methods, photodynamic therapy (PDT) is a minimally invasive and tumor-targeting specific treatment method, which can not only produce photochemical reactions to destroy tumor cells and trigger immune responses, but also use its fluorescence to support photodynamic diagnosis and fluorescence-guided surgery. Clinical studies have shown that photodynamic diagnosis and photodynamic fluorescence-guided tumor cell reduction, PDT and its combination therapy have great therapeutic potential, and have been recognized and gradually applied in recent years. This article reviews the current status of PDT in the treatment of advanced ovarian cancer, and discusses its possible application prospects in order to provide a safe and effective treatment for the comprehensive treatment of clinical ovarian cancer.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.