[Clinical observation of the subthreshold micropulse laser combined with ranibizumab for treatment of diabetic macular edema].

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)µm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)µm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

[The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation].

Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

[While the priest climbs a post, the devil climbs ten: major biological threats from parasite and vector to malaria control and elimination].

Malaria is one of the most serious mosquito-borne infectious diseases in the world. The global malaria control progress has stalled in recent years, which is largely due to the biological threats from the malaria pathogen Plasmodium and the vector Anopheles mosquitoes. This article provides an overview of biological threats to global malaria elimination, including antimalarial drug resistance, deletions in the malaria rapid diagnostic test target P. falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes, vector insecticide resistance and emergence of invasive vector species, so as to provide insights into malaria and vector research and the formulation and adjustment of the malaria control and elimination strategy.

[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].

Objective: To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. Methods: In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (Ztrend=7.30, Ptrend<0.001), and the standardized incidence rate also showed an upward trend (Ztrend=3.92, Ptrend=0.004). The crude incidence rate of women was higher than that of men in all years (all P values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all P values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (P<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all P values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all P<0.05), and there was no significant difference between urban and rural residents in most years (P>0.05). The incidence of SAH increased with age (Ptrend<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's I>0, P<0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. Conclusions: The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.

The Relationship between the Level of Coagulative Function Hypertensive Disorder Complicating Pregnancy.

BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.

[Application and progress of ablation therapy for large liver cancer].

Primary liver cancer is one of the most common malignant tumors. A liver tumor is defined as a large cancer when its diameter is ≥5 cm. Resection surgical therapy can be performed only on a small portion of large cancers because of its own features. As a result, non-resection surgical therapy has become a hot and difficult issue of widespread concern. In recent years, with the development of ablation technology, research on the use of ablation alone and ablation combined with other modalities for the treatment of large liver cancer has continued to deepen, and good clinical results have been achieved. Although there are many reports on ablation treatment for large liver cancer, there are currently no standardized treatment guidelines, and there are still controversies about treatment strategies. This article reviews the development of ablation therapy, the current status of single and combined ablation therapy, the prevention of related complications, and other aspects of large liver cancer.

[Experimental study on evaluating renal redox metabolism in renal ischemia-reperfusion injury using GluCEST imaging with 3.0 T MRI].

Objective: To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI). Methods: Rabbits in the IRI group (n=56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group (n=8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTRasym) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTRasym and ROS were analyzed. Results: The MTRasym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla (t=8.16, P<0.001; t=4.78, P=0.002; t=4.94, P=0.002; t=5.76, P=0.001, t=6.68, P<0.001; t=6.40, P<0.001; t=5.16, P=0.001; t=3.30, P=0.013). The MTRasym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P<0.05). The MTRasym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P<0.05). The MTRasym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P<0.05). The MTRasym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P=0.008). The MTRasym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P<0.05]. The MTRasym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P<0.05). The MTRasym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS (ρ=-0.889, P<0.001; ρ=-0.784, P<0.001). Conclusion: 3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

[Interpretation of the surgical treatment of pancreatic cancer of the 2024 edition of the NCCN guidelines].

Pancreatic cancer is a highly malignant tumor in the digestive system, and radical surgery is the only possible means to cure pancreatic cancer at present. In the past decade, pancreatic surgery has been developing rapidly, with various new technologies and concepts emerging, among which the use of minimally invasive techniques and the popularization of neoadjuvant therapy concepts are the most notable. At the same time, the surgical treatment of pancreatic cancer still has a long way to go, and many problems need to be solved urgently. This article introduces the surgical treatment of pancreatic cancer in the 2024 edition of the NCCN guidelines, focusing on minimally invasive and open surgical treatments, expanded lymph node dissection, combined vascular resection and reconstruction, surgical treatment of pancreatic neck cancer and neoadjuvant therapy, and briefly discussing the unresolved issues.

[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

[Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia].

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

[Progress in PD-1/PD-L1, PD-L2 signaling pathway and its role in host anti-tuberculosis immunity].

Programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, expressed on a variety of immune cells, play multiple regulatory roles in the host immune response to Mycobacterium tuberculosis infection. In this study, we reviewed that the regulatory roles of PD-1/PD-L1, PD-L2 signaling in the host adaptive immune response, such as the innate response of macrophages, and the interaction between T cells and macrophages in response to MTB. In addition, during MTB infection, PD-1/PD-L1, PD-L2 signaling is also involved in the host inflammatory response, as well as the potential roles of PD-1/PD-L1, PD-L2 in the diagnosis and treatment of tuberculosis.

[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

[Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging].

Objective: To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation. Methods: A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups. Results: The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants (P < 0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants (P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion: LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.

Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary ß-glucan-induced inflammatory adaptation.

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal ß-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, ß-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.

[Current status and prospects of genetic research on IgA nephropathy].

IgA nephropathy is the most common primary glomerulonephritis worldwide, and genetic factors may play an important role in its pathogenesis. Following candidate gene association analysis and genome-wide linkage study, genome-wide association studies (GWAS) have found multiple susceptibility genes related to the pathogenesis and clinical phenotype of IgA nephropathy. Meanwhile, structural variation and epigenetic changes are also closely related to IgA nephropathy. Genetic variants have been found to explain about 11% of its heritability. In the current era of genomic medicine, how to find more susceptible genes/loci, whole genome sequencing studies (WGS) provide clues to further understand the genetic variation of IgA nephropathy. How to find the cell type-specific susceptibility genes associated with IgA nephropathy, multi-omics studies will conduct comprehensive analysis via single-cell sequencing, expression quantitative trait locus (eQTL) and genomics to find the pathogenic genes and offer insights into the development of targeted drugs, which will be the trend and direction of future research.

The Clinical Significance of Subtle Distal Fallopian Tube Abnormalities: A Multicentre Prospective Observational Study.

Background: Subtle distal fallopian tube abnormalities are a group of diseases characterised by small variations in tubal anatomy. The clinical significance of these abnormalities need to be studied. Objectives: The purpose of this multicentre prospective observational study was to investigate whether subtle distal fallopian tube abnormalities are related to infertility and endometriosis. Materials and Methods: The investigation was carried out in five medical centres in China and France from February to July 2021 and included reproductive-age patients who underwent gynaecological laparoscopy. Subtle abnormalities included Hydatid of Morgagni (HM) , fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis, and accessory fallopian tube. Results: 642 patients were enrolled in the study and 257 (40.0%) were diagnosed with subtle tube abnormalities. Hydatid of Morgagni was the most common abnormality (22.7%; n=146), followed by fimbrial agglutination (19.8%; n=127), tubal diverticula (6.9%; n=44), accessory tube (2.0%; n=13), and tubal accessory ostium (1.9%; n=12). Fimbrial phimosis was the least common abnormality (0.3%; n=2). The prevalence of subtle fallopian tube abnormalities was significantly higher among infertile patients (188/375, 50.1%) than those without history of infertility (69/267, 25.8%, ᶍ2=38.332, P=0.000). 209 patients were diagnosed with endometriosis during surgery, and the prevalence of subtle abnormalities was significantly higher in the endometriosis group than in those without endometriosis (61.2%, [128/209] vs. 29.8% [129/433], ᶍ2=58.086, P=0.000). Conclusions: Higher prevalence of subtle tubal abnormalities suggests that they may contribute to infertility. They are highly related to endometriosis and indicate fimbrial abnormalities of endometriosis. What is new?: This is the largest multicentre study to investigate the subtle distal fallopian tube abnormalities in infertile women. Compared to previous studies, this study includes the main subtle distal abnormalities and the control group patients without a history of infertility.

[Epidemiological characteristics of diarrheagenic Escherichia coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai, 2014-2021].

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E. ) coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai and provide evidence for the development of disease control strategies. Methods: Based on multistage systematic sampling, diarrhea surveillance was conducted in 22 sentinel hospitals in Shanghai, the information about cases' demographic, clinical, and epidemiological characteristics were collected. Stool samples were collected for the detection and typing of diarrheagenic E. coli by local centers for disease control and prevention. The positive rate of diarrheagenic E. coli in different populations and seasons from 2014 to 2021 were analyzed. Statistical analysis was conducted by using χ2 test. Results: In 15 185 diarrhea cases, 8.05% (1 222/15 185) were positive for diarrheagenic E. coli. The positive rate was higher in men (8.74%, 684/7 824) than in women (7.31%, 538/7 361). The positive rate was highest in age group 15-29 years (9.14%, 335/3 665) and the annual positive rate was highest in 2021 (10.21%, 83/813), the differences were all significant (P<0.05). In the 1 264 strains of diarrheagenic E. coli analyzed through PCR, enterotoxingenic E. coli was the most frequently identified pathogen (50.24%, 635/1 264), followed by enteroadhesive E. coli (27.93%, 353/1 264), and enteropathogenic E. coli (21.36%, 270/1 264). The positive rate of diarrheagenic E. coli showed obvious seasonality with peak in summer (13.92%, 774/5 562) (χ2=495.73, P<0.001). Conclusions: Diarrheagenic E. coli has become a prominent pathogen in infectious diarrhea cases in Shanghai, the disease can occur all the year round with incidence peak during summer and autumn. Predominant subtypes included enterotoxingenic E. coli, enteroadhesive E. coli and enteropathogenic E. coli. Targeted prevention and control strategies are needed for diarrheagenic E. coli-induced infectious diarrhea in different age groups, seasons and for different types of infections.