Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

Objective To compare the difference in the efficacies of arthroscopic microfracture operation for talar osteochondral injuries with hyperuricemia and non-hyperuricemia,and to explore the correlation be-tween blood urate level and efficacy.Methods Fifty-three patients with talar osteochondral lesions meeting the inclusion and exclusion criteria from February 2015 to August 2021 were selected as the research subjects and divided into the hyperuricemia group (22 cases) and non-hyperuricemia group (31 cases) according to whether or not the preoperative blood uric acid level exceeding 420 μmol/L.The joint range of motion (ROM),visual analog scale (VAS) score,American Foot and Ankle Surgery Society (AOFAS) score,mag-netic resonance score of cartilage repair tissue (MOCART) score and postoperative satisfaction before and af-ter surgery were compared between the two groups.Results The preoperative blood uric acid level in the hy-peruricemia group was higher than that in non-hyperuricemia group,and the difference was statistically signif-icant[(504.35±86.40)μmol/L vs.(332.56±45.80)μmol/L,P<0.05].The ROM score,VAS score and AOFAS score in postoperative 1 year follow up and last follow up in the two groups were significantly im-proved compared with before operation (P<0.001).The AOFAS scores before operation,in postoperative 1 year and postoperative last follow up in the hyperuricemia group were lower than those in the non-hyperurice-mia group (P<0.05).The VAS scores before operation and postoperative last follow up in the hyperuricemia group were higher than those in the non-hyperuricemia group (P<0.05).The uric acid level was negatively correlated with the postoperative AOFAS score (r2=0.076,P=0.041).The MOCART score in postopera-tive last follow up in the hyperuricemia group was lower than that in the non-hyperuricemia group,and the difference was statistically significant (P<0.05).The cartilage defect repair and filling degree and the fusion of repaired tissue with adjacent cartilage had statistical differences between the hyperuricemia group and non-hyperuricemia group (P<0.05).Conclusion Arthroscopic microfracture operation in treating talar osteo-chondral injuries has good clinical effect,the postoperative clinical effect in the patients with complicating hy-peruricemia is lower than that in the patients with non-hyperuricemia and the blood uric acid level is negative-ly correlated with the AOFAS score after microfracture surgery.

Objective To analyze the diversity and composition changes of gut fungal communities between mouse model of total parental nutrition(TPN)and normal control mice.Methods After mouse model of TPN was constructed,fresh feces were collected from TPN mice(n=5)and normal control mice(n=5).Internal transcribed spacer(ITS)DNA sequencing was applied to determine intestinal fungi,and then bioinformatics analysis was conducted to identify the differences in fungal diversity,structure,and functional properties between the 2 groups of mice.Results There were significant differences in Alpha diversity(P＜0.05)and Beta diversity(P＜0.01)of intestinal fungi between the 2 groups.In the TPN model group,the relative abundances of Candida,Penicillium,Aspergillus and Talaromyces were obviously reduced(all P＜0.01).LEfSe analysis indicated that the above 4 strains were notably enriched in the normal control mice.Conclusion TPN mice exhibit characteristic changes in the composition of gut fungal flora compared to normal control mice.Dysfunction of gut fungal community may promote the occurrence of TPN related complications,and regulating the balance of gut fungal community may become a new strategy for preventing TPN related complications.

Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

OBJECTIVE: To retrospectively analyze the results of chromosomal microarray analysis (CMA) and parental origins of unbalanced translocations among 17 patients, so as to provide reference for their genetic counseling. METHODS: The results of CMA for 7 001 samples tested in Chengdu Women and Children's Central Hospital from January 2019 to January 2022 were retrospectively reviewed. Unbalanced reciprocal translocation was defined as two non-homologous chromosomes with lost and gained segments respectively or both with gained segments, and their parental origins were identified by parental chromosomal karyotyping and/or fluorescence in situ hybridization (FISH). RESULTS: In total 17 unbalanced translocations were identified. In three cases, two non-homologous chromosomes both had gained segments, which constituted a derivative chromosome, with the total number of chromosomes being 47. In the remaining 14 cases, there was a terminal deletion on one chromosome and a terminal duplication on the other, 10 of which were confirmed by karyotyping, with the total number of chromosomes being 46. In the derivative chromosome, the lost segment was replaced by a gained segment from another chromosome. Among 15 cases undergoing parental origin analysis, 12 had paternal or maternal chromosomal abnormalities, including 11 balanced translocations and 1 unbalanced translocation. The unbalanced gametes therefore may form through meiosis. In 3 cases, the parental chromosomes were normal, indicating a de novo origin. CONCLUSION Discovery of terminal duplication and deletion or gained segments on two non-homologous chromosomes by CMA is suggestive of parental balanced translocation, which can facilitate genetic counseling and assessment the recurrence risk for subsequent pregnancies.
Child ; Pregnancy ; Humans ; Female ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Translocation, Genetic ; Microarray Analysis ; Chromosomes

Stroke-like symptoms and cognitive impairment caused by cerebral small vessel diseases will bring heavy burden to families and society. Therefore, early diagnosis and treatment of cerebral small vessel diseases are particularly important. This article reviews the diagnosis and treatment of cerebral small vessel diseases.

Post-stroke anxiety is one of the most common and important complications in patients with stroke, which can seriously affect the rehabilitation, daily life and work of patients with stroke. This article reviews the epidemiology, clinical characteristics, risk factors and predictors, pathophysiological mechanism, prevention and treatment of post-stroke anxiety.

Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized, the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.