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.

AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

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 explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

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 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.