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Objective:To analyze the differences in endoscopic and pathological features in autoimmune gastritis (AIG) patients with and without Helicobacter pylori ( HP) infection, and to explore the effects of HP on the clinical manifestations and disease development in AIG patients. Methods:From January 2022 to April 2024, 174 AIG patients who visited Beijing Hospital and met the 2022 AIG diagnostic criteria established by Japanese Gastroenterological Endoscopy Society were enrolled and divided into the HP-infected group (including current and previous infection, 77 cases) and the HP-unifected group (97 cases). The general clinical data, laboratory examinations endoscopic findings, and pathological characteristics of the two groups were analyzed. Independent sample t-test and chi-square test were used for statistical analyses. Results:The vitamin B 12 level of HP-infected group was higher than that of HP-unifected group ((573.81±460.77) ng/L vs. (411.86±335.00) ng/L), and the difference was statistically significant ( t=-2.57, P=0.011). The average red blood cell volume of HP-infected group was lower than that of HP-unifected group ((87.30±8.86) fL vs. (98.50±49.82) fL), and the difference was statistically significant ( t=2.16, P=0.033). The proportion of intestinal metaplasia in gastric fundus in HP-infected group was lower than that in HP-unifected group (50.6% (39/77) vs. 73.2% (71/97)), and the difference was statistically significant ( χ2=9.38, P=0.002). Conclusion:HP infection in AIG patients may delay the malabsorption of vitamin B 12 and the occurrence of intestinal metaplasia in gastric fundus.

BACKGROUND:Osteoarthritis is a common degenerative joint disease,and the etiology and development of its pathogenesis are still unclear.Timely diagnosis and treatment of early osteoarthritis are crucial,and there is currently no definite and effective method.Extracellular vesicles come from a wide range of sources,including non-coding RNAs such as small RNAs,circular RNAs,and long chain non-coding RNAs.Extracellular vesicles non-coding RNAs can be directly delivered from primitive cells to neighboring or remote cells,regulating cell activity through intercellular communication and playing an important regulatory role in reshaping the bone and joint microenvironment.OBJECTIVE:To summarize the intervention effects of exosome-derived non-coding RNAs on the joint microenvironment of osteoarthritis and the progress made in clinical application,and to clarify the potential of exosome-derived non-coding RNAs in the diagnosis and treatment of osteoarthritis.METHODS:Search terms "exosomes,non-coding RNA,osteoarthritis,application,signal pathway,synovial fluid,cartilage cells,cartilage matrix,subchondral,mechanism" were used for the search on PubMed database.Finally,66 related articles were included for review analysis.RESULTS AND CONCLUSION:(1) Exosome-derived non-coding RNAs play an important regulatory role in the joint microenvironment during the pathogenesis of osteoarthritis,mainly reflected in:exosome non-coding RNAs regulating the inflammatory response in the joint,degeneration of chondrocytes and cartilage matrix,subchondral bone remodeling,and intercellular communication.(2) The non-coding RNAs in exosomes can serve as biomarkers for osteoarthritis,aiding in the early diagnosis and monitoring of disease progression and prognosis.(3) Exosome non-coding RNAs serve as therapeutic targets for osteoarthritis.Exosomes carry miRNAs to the articular chondrocytes and cartilage matrix to play a regulatory role.(4) Exosomes non-coding RNAs can improve the effect of cartilage tissue engineering by regulating gene expression and promoting intercellular communication to repair or regenerate damaged cartilage.(5) In future research,researchers should continue to explore the intervention mechanism of non-coding RNAs derived from exosomes on osteoarthritis,and apply them to clinical practice in combination with the latest research outcomes in cartilage tissue engineering,which will effectively help solve the pain of osteoarthritis patients.

Objective:To analyze the differences in endoscopic and pathological features in autoimmune gastritis (AIG) patients with and without Helicobacter pylori ( HP) infection, and to explore the effects of HP on the clinical manifestations and disease development in AIG patients. Methods:From January 2022 to April 2024, 174 AIG patients who visited Beijing Hospital and met the 2022 AIG diagnostic criteria established by Japanese Gastroenterological Endoscopy Society were enrolled and divided into the HP-infected group (including current and previous infection, 77 cases) and the HP-unifected group (97 cases). The general clinical data, laboratory examinations endoscopic findings, and pathological characteristics of the two groups were analyzed. Independent sample t-test and chi-square test were used for statistical analyses. Results:The vitamin B 12 level of HP-infected group was higher than that of HP-unifected group ((573.81±460.77) ng/L vs. (411.86±335.00) ng/L), and the difference was statistically significant ( t=-2.57, P=0.011). The average red blood cell volume of HP-infected group was lower than that of HP-unifected group ((87.30±8.86) fL vs. (98.50±49.82) fL), and the difference was statistically significant ( t=2.16, P=0.033). The proportion of intestinal metaplasia in gastric fundus in HP-infected group was lower than that in HP-unifected group (50.6% (39/77) vs. 73.2% (71/97)), and the difference was statistically significant ( χ2=9.38, P=0.002). Conclusion:HP infection in AIG patients may delay the malabsorption of vitamin B 12 and the occurrence of intestinal metaplasia in gastric fundus.

BACKGROUND:Osteoarthritis is a common degenerative joint disease,and the etiology and development of its pathogenesis are still unclear.Timely diagnosis and treatment of early osteoarthritis are crucial,and there is currently no definite and effective method.Extracellular vesicles come from a wide range of sources,including non-coding RNAs such as small RNAs,circular RNAs,and long chain non-coding RNAs.Extracellular vesicles non-coding RNAs can be directly delivered from primitive cells to neighboring or remote cells,regulating cell activity through intercellular communication and playing an important regulatory role in reshaping the bone and joint microenvironment.OBJECTIVE:To summarize the intervention effects of exosome-derived non-coding RNAs on the joint microenvironment of osteoarthritis and the progress made in clinical application,and to clarify the potential of exosome-derived non-coding RNAs in the diagnosis and treatment of osteoarthritis.METHODS:Search terms "exosomes,non-coding RNA,osteoarthritis,application,signal pathway,synovial fluid,cartilage cells,cartilage matrix,subchondral,mechanism" were used for the search on PubMed database.Finally,66 related articles were included for review analysis.RESULTS AND CONCLUSION:(1) Exosome-derived non-coding RNAs play an important regulatory role in the joint microenvironment during the pathogenesis of osteoarthritis,mainly reflected in:exosome non-coding RNAs regulating the inflammatory response in the joint,degeneration of chondrocytes and cartilage matrix,subchondral bone remodeling,and intercellular communication.(2) The non-coding RNAs in exosomes can serve as biomarkers for osteoarthritis,aiding in the early diagnosis and monitoring of disease progression and prognosis.(3) Exosome non-coding RNAs serve as therapeutic targets for osteoarthritis.Exosomes carry miRNAs to the articular chondrocytes and cartilage matrix to play a regulatory role.(4) Exosomes non-coding RNAs can improve the effect of cartilage tissue engineering by regulating gene expression and promoting intercellular communication to repair or regenerate damaged cartilage.(5) In future research,researchers should continue to explore the intervention mechanism of non-coding RNAs derived from exosomes on osteoarthritis,and apply them to clinical practice in combination with the latest research outcomes in cartilage tissue engineering,which will effectively help solve the pain of osteoarthritis patients.

Purpose The purpose of this study was to in-vestigate programmed death ligand-1(PD-L1)expression in gastric adenocarcinoma(GAC)patients and the consistency of immunohistochemical(IHC)detection of four different clones of PD-L1 antibodies,so as to provide reference for the gradual standardization of PD-L1 IHC detection in gastric adenocarcino-ma and subsequent clinical studies.Methods This study col-lected surgically resected and pathologically confirmed specimens from 286 gastric adenocarcinoma patients,and specimens were stained with four antibodies:PD-L1 22C3,SP263,E1L3N and SP142.The consistency of the antibodies was statistically ana-lyzed under different critical values using two scoring criteria:comprehensive positive score(CPS)and tumor proportion score(TPS).Results Regardless of the TPS and CPS cut-off val-ues,the positive rate of 22C3 was the highest among the four an-tibodies.Consistency analysis showed that E1L3N had good con-sistency with SP142(κ=0.612)and SP263(κ=0.660)only when the cut-off value of CPS positive was 1.In addition,the consistency between the other antibodies was only moderate or poor.Conclusion The four PD-L1 antibodies exhibited incon-sistent concordance across various TPS and CPS positive thresh-olds,so it is not recommended to exchange reagents during clini-cal testing of GAC and the test results shall be documented in accordance with the specification.

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

Objective:To investigate the effect of transurethral green laser prostate enucleation (GreenLEP) in the treatment of benign prostate hyperplasia (BPH) with detrusor underactivity (DU).Methods:The clinical data of 157 BPH patients treated with GreenLEP at Zhejiang Provincial People's Hospital from June 2019 to June 2020 were retrospectively analysed. The average age of the patients was (73.2±7.9) years old, with disease duration of 4(2, 8) years. Prior to surgery, all patients underwent comprehensive urodynamic studies and prostate ultrasonography (or enhanced MRI). Preoperative prostate volume was 42.1(34.2, 59.4) ml, international prostate symptom score (IPSS) was (27.9±3.4), quality of life (QOL) score was (5.1±0.8), preoperative residual urine volume (PVR) was 40.0(20.0, 80.0) ml, and preoperative maximum urinary flow rate (Q max) was 4.0(2.0, 7.0) ml/s. Patients were stratified into DU and non-DU groups using a bladder contractility index (BCI) threshold of less than 100 to diagnose DU. The cohort comprised 76 individuals in the DU group and 81 in the non-DU group. At the three-month postoperative juncture, a follow-up assessment was conducted on the patients, focusing on the evolution of subjective metrics (IPSS, QOL) and objective parameters (PVR, Q max). This study defined successful treatment outcomes at the 3-month mark as achieving PVR<20 ml and Q max>10 ml/s. Cases not meeting these criteria were categorized as treatment failure. Based on treatment outcomes, receiver operator characteristic (ROC) curve were plotted to identify the optimal cutoff value of BCI for predicting treatment efficacy. Subsequently, DU patients were classified into mild and severe DU groups based on this optimal BCI threshold. The differences of subjective indicators (IPSS, QOL) and objective parameters (PVR, Q max) preoperatively among non-DU, mild DU, and severe DU groups, as well as changes in these indices three months postoperatively were analyzed. Results:All 157 surgeries were successfully completed, with a median hospital stay of 6(5, 8) days. At the 3-month postoperative follow-up, 78 patients were deemed treatment successes and 3 as failures in non-DU group, 64 were successful and 12 failed in DU group. Utilizing ROC curve analysis, the BCI was optimally set at 57.5. This stratification resulted in 56 cases classified as mild DU (57.5≤BCI<100) group and 20 cases as severe DU (BCI<57.5) group. A comparative analysis of the three patient cohorts, revealed no significant statistical variation in terms of age, disease duration, or prostate volume ( P>0.05). In the non-DU, mild DU, and severe DU groups, IPSS were (26.8±3.4), (28.6±3.0), and (30.6±2.4) respectively, QOL sores were (4.9±0.9), (5.2±0.7), and (5.7±0.5) respectively, PVR volumes were 50.0(20.0, 90.0), 20.0(10.0, 50.0), and 60.0(27.5, 165.0) ml respectively, Q max were 4.0(2.0, 7.0), 5.0(4.0, 6.0), and 0(0, 2.3) ml/s respectively. Preoperative IPSS and QOL were significantly lower in the non-DU group compared with mild and severe DU groups ( P<0.05). Mild DU group had lower preoperative IPSS and QOL than the severe DU group ( P<0.05). Preoperative PVR in the mild DU group was less than that in both non-DU and severe DU groups ( P<0.05), but there was no statistically significant difference in preoperative PVR between non-DU and severe DU groups ( P>0.05). Preoperative Q maxof non-DU and mild DU groups was significantly higher than that of severe DU group ( P<0.05), with no significant difference between non-DU and mild DU ( P>0.05). Three months after surgery, IPSS scores of non-DU group, mild DU group and severe DU group were (12.5±4.7), (14.9±3.6) and (18.8±4.1), respectively. QOL scores of the 3 groups improved to (1.1±0.4), (1.2±0.5) and (1.9±1.0), respectively. PVR was 0 in non-DU and mild DU, and 20.0 (19.5, 61.3) ml in severe DU. Q max of the 3 groups were improved to 22.0(18.0, 27.0), 17.0(14.0, 22.3), and 9.0(6.8, 13.0) ml/s, respectively. Significant improvements of subjective symptoms (IPSS, QOL) and objective parameters (PVR, Q max) were observed in non-DU and mild DU group compared with preoperative( P<0.05). Significant improvements of IPSS, QOL and Q max ( P<0.05) but not PVR ( P=0.14)were observed in severe DU group. Additionally, significant differences were noted in PVR and Q max changes among the three groups ( P<0.05), but not in IPSS and QOL changes ( P>0.05). The absolute value of PVR and Q max changes in the non-DU group were higher than those in the mild DU group and the severe DU group ( P<0.05). Additionally, the change of Q max in mild DU group was significantly higher than that in severe DU group ( P<0.05). Conclusions:BPH patients with different degrees of DU can benefit from GreenLEP surgery, but for BPH patients with severe DU (BCI < 57.5), the improvements in PVR and Q max are less than that in the non-DU group.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).