Background and Aims:For patients with mid-to-low rectal cancer who achieve clinical complete response(cCR)or near-cCR after neoadjuvant chemoradiotherapy(nCRT),the key concern for both clinicians and patients is how to preserve anal function as much as possible without significantly compromising oncological outcomes.This study was performed to evaluate the safety and feasibility of local excision as an anus-preserving approach in rectal cancer patients with cCR or near-cCR.Methods:A retrospective analysis was conducted on 51 patients with mid-to-low rectal cancer who underwent local resection after achieving cCR or near-cCR following nCRT at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between March 2014 and July 2023.The clinical characteristics,imaging and pathological findings,surgical outcomes,as well as oncological and functional results were reviewed.Results:Among the 51 patients,34 were male and 17 were female,with a mean age of 61±14 years.Pre-nCRT imaging staging showed:cT1-2N0 in 12 cases(23.5％),cT3N0 in 13 cases(25.5％),cT1-3N0-1 in 19 cases(37.4％),and cT1-3N2 in 7 cases(13.7％).The average tumor distance from the anal verge was(4.5±1.1)cm.After achieving cCR or near-cCR following nCRT,all patients underwent local resection:40 cases(78.4％)underwent transanal endoscopic microsurgery(TEM),7 cases(13.7％)underwent transanal minimally invasive surgery(TAMIS),and 4 cases(7.8％)underwent conventional transanal local excision.The postoperative complication rate was 27.5％(14/51),with 71.4％classified as Clavien-Dindo grade Ⅰ.Postoperative histopathology showed ypT0 in 26 cases(51.0％),ypT1 in 8 cases(15.7％),ypT2 in 16 cases(31.4％),and ypT3 in 1 case(2.0％).The concordance rate between pathological results and preoperative imaging was 54.9％.Over a median follow-up of 60 months(range:34-79),there were 4 cases(7.8％)of local recurrence,12 cases(23.5％)of distant metastasis,and 5 cancer-related deaths(9.8％).Six months postoperatively,both the Wexner score and the low anterior resection syndrome(LARS)score significantly improved compared to post-nCRT values[Wexner:1(0-2)vs.2(1-5);LARS:3.3±5.75 vs.4.3±6.86;both P＜0.01].Conclusion:For patients with mid-to-low rectal cancer who achieve cCR or near-cCR after nCRT,local en bloc resection of the bowel wall lesions enables accurate assessment of residual tumor status and facilitates personalized subsequent treatment,potentially sparing some patients from radical surgery.Local resection can be a viable anus-preserving option for patients who are unfit for or strongly averse to radical resection.However,local excision cannot replace radical surgery,and its precise indications warrant further investigation.

OBJECTIVE: To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics. METHODS: A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J). RESULTS: A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c.1024C>A (p.L342M) and ASS1: c.826A>G (p.M276V), c.695C>T (p.P232L) and c.694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
Humans ; Infant, Newborn ; Tandem Mass Spectrometry/methods* ; Urea Cycle Disorders, Inborn/diagnosis* ; Neonatal Screening/methods* ; Genetic Testing/methods* ; Female ; Retrospective Studies ; Male ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; Mutation ; Carbamoyl-Phosphate Synthase (Ammonia)/genetics* ; Ornithine Carbamoyltransferase/genetics*

Hyperphenylalaninemia (HPA) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase, characterized by significantly elevated phenylalanine levels. Conventional mechanisms, such as neurotransmitter deficiency and dysmyelination, fail to fully explain the progressive neurological damages associated with HPA. Meanwhile, ferroptosis, an emerging form of iron-dependent regulated cell death, has proven to play an important role in neurodegenerative diseases. We hereby propose a hypothesis that tetrahydrobiopterin (BH4) depletion in HPA may lead to the collapse of intracellular antioxidant defenses. This process could induce ferroptosis, thereby serving as a pivotal mechanism underlying HPA-related neurological injury. This review has systematically summarized the pathological mechanisms of HPA, the biological features of ferroptosis, and the bridging role of BH4 between them, thereby establishing a novel "HPA-BH4-ferroptosis" theoretical framework and providing a rationale for developing new therapeutic strategies targeting ferroptosis.
Ferroptosis ; Humans ; Biopterins/deficiency* ; Phenylketonurias/pathology* ; Animals

Objective:To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics.Methods:A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J).Results:A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c. 1024C>A (p.L342M) and ASS1: c. 826A>G (p.M276V), c.695C>T (p.P232L) and c. 694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.

Background and Aims:For patients with mid-to-low rectal cancer who achieve clinical complete response(cCR)or near-cCR after neoadjuvant chemoradiotherapy(nCRT),the key concern for both clinicians and patients is how to preserve anal function as much as possible without significantly compromising oncological outcomes.This study was performed to evaluate the safety and feasibility of local excision as an anus-preserving approach in rectal cancer patients with cCR or near-cCR.Methods:A retrospective analysis was conducted on 51 patients with mid-to-low rectal cancer who underwent local resection after achieving cCR or near-cCR following nCRT at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between March 2014 and July 2023.The clinical characteristics,imaging and pathological findings,surgical outcomes,as well as oncological and functional results were reviewed.Results:Among the 51 patients,34 were male and 17 were female,with a mean age of 61±14 years.Pre-nCRT imaging staging showed:cT1-2N0 in 12 cases(23.5％),cT3N0 in 13 cases(25.5％),cT1-3N0-1 in 19 cases(37.4％),and cT1-3N2 in 7 cases(13.7％).The average tumor distance from the anal verge was(4.5±1.1)cm.After achieving cCR or near-cCR following nCRT,all patients underwent local resection:40 cases(78.4％)underwent transanal endoscopic microsurgery(TEM),7 cases(13.7％)underwent transanal minimally invasive surgery(TAMIS),and 4 cases(7.8％)underwent conventional transanal local excision.The postoperative complication rate was 27.5％(14/51),with 71.4％classified as Clavien-Dindo grade Ⅰ.Postoperative histopathology showed ypT0 in 26 cases(51.0％),ypT1 in 8 cases(15.7％),ypT2 in 16 cases(31.4％),and ypT3 in 1 case(2.0％).The concordance rate between pathological results and preoperative imaging was 54.9％.Over a median follow-up of 60 months(range:34-79),there were 4 cases(7.8％)of local recurrence,12 cases(23.5％)of distant metastasis,and 5 cancer-related deaths(9.8％).Six months postoperatively,both the Wexner score and the low anterior resection syndrome(LARS)score significantly improved compared to post-nCRT values[Wexner:1(0-2)vs.2(1-5);LARS:3.3±5.75 vs.4.3±6.86;both P＜0.01].Conclusion:For patients with mid-to-low rectal cancer who achieve cCR or near-cCR after nCRT,local en bloc resection of the bowel wall lesions enables accurate assessment of residual tumor status and facilitates personalized subsequent treatment,potentially sparing some patients from radical surgery.Local resection can be a viable anus-preserving option for patients who are unfit for or strongly averse to radical resection.However,local excision cannot replace radical surgery,and its precise indications warrant further investigation.

Objective:To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics.Methods:A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J).Results:A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c. 1024C>A (p.L342M) and ASS1: c. 826A>G (p.M276V), c.695C>T (p.P232L) and c. 694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.

Objective:To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers.Methods:This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two‐thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left‐sided colon cancers (LCCs). Clinicopathological features were compared using the χ 2 test or Mann‐Whitney U test. Survival was estimated by Kaplan‐Meier curves and the log‐rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results:The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ 2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m 2 vs. 23.2 [21.3, 25.5] kg/m 2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ 2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ 2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ 2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow‐up time for all patients was 48 (range 33, 59) months. The log‐rank test revealed no significant differences in disease-free survival (DFS) ( P=0.668) or overall survival (OS) ( P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204?0.862, P=0.018), whereas a higher proportion of T3‐4 (HR=2.178, 95%CI: 1.089?4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443?3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115?3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146?0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103?1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log‐rank test revealed no significant differences in DFS ( P=0.343) or OS ( P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS ( P=0.047) and OS ( P=0.040) than did patients with pMMR. Conclusions:Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Objective:To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers.Methods:This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two‐thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left‐sided colon cancers (LCCs). Clinicopathological features were compared using the χ 2 test or Mann‐Whitney U test. Survival was estimated by Kaplan‐Meier curves and the log‐rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results:The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ 2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m 2 vs. 23.2 [21.3, 25.5] kg/m 2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ 2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ 2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ 2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow‐up time for all patients was 48 (range 33, 59) months. The log‐rank test revealed no significant differences in disease-free survival (DFS) ( P=0.668) or overall survival (OS) ( P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204?0.862, P=0.018), whereas a higher proportion of T3‐4 (HR=2.178, 95%CI: 1.089?4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443?3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115?3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146?0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103?1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log‐rank test revealed no significant differences in DFS ( P=0.343) or OS ( P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS ( P=0.047) and OS ( P=0.040) than did patients with pMMR. Conclusions:Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Cerebrovascular diseases pose a serious threat to human health.According to the latest epidemiological data,stroke is one of the leading causes of death and disability among adults worldwide.Acute ischemic stroke(AIS),which is caused by local circulatory disorders in the brain,accounts for over 80%of all strokes and is the most common type of stroke.Due to extensive damage to the cerebral cortex or direct involvement of the autonomic nerve centers and pathways caused by AIS,the balance between the sympathetic and parasympathetic nervous systems is disturbed(with a predominance of sympathetic activation).Therefore,the organs targeted by the downstream pathways of the sympathetic and parasympathetic nervous systems are affected by the neurotransmitters they secrete,resulting in a range of systemic complications(such as cardiac complications,stroke-related infections,gastrointestinal complications,acute kidney injury,metabolic changes,and sexual dysfunction).These systemic pathological changes,in turn,affect the progression of AIS,thereby exacerbating brain damage or directly leading to patient death.Treatments targeting imbalances in the autonomic nervous system may play a role in reducing complications and improving the prognosis of AIS.This article reviews the systemic effects of autonomic dysfunction following AIS and its mechanisms,providing insights for the treatment of AIS and intervention of systemic complications.

In order to improve the effectiveness of private class inquiry with the development of information teaching, the smart teaching platform has been established, with instructional management, curriculum setting, teacher preparation, classroom application, supervision and monitoring modules. Taking the platform as the medium, the small class inquiry learning community of entity curriculum is constructed between students and the teachers. In the eight-year medical teaching, the content of learning cycle is designed according to the entity curriculum, which is issued on cloud platform before class, in class and after class. Students learn basic concepts by themselves in the learning community, explore the application of knowledge under the guidance of teachers, and expand knowledge in class or after class. After having test in teaching procedure, the small class learning community based on smart teaching cloud platform has a submission rate, interaction rate and score rate of more than 90%. It can not only make full use of the advantages of information-based teaching resources, but also build face-to-face learning community in the course teaching, reflecting the emotional interaction of personalized teaching. It's suggested that new approaches to teaching should be student-centered and activity-based, engaging students actively in the learning process, which can promote students' autonomous learning ability and innovative thinking ability.