[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.

OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides(TSG)on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ(AngⅡ).METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups:control group,AngⅡgroup(2 μmol/L),TSG group(7.5 μg/mL),PFK-015 group[6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)inhibitor,10 nmol/L],and TSG+PFK-015 group(TSG 7.5 μg/mL+PFK-015 10 nmol/L).The surface area,protein synthesis,energy metabolism-related indicators[free fatty acid(FFA),coenzyme A(CoA),acetyl coenzyme A(acetyl-CoA)],and the expressions of glycolysis-related factors[hypoxia-inducible factor 1α(HIF-1α),glucose transporter protein 4(GLUT-4),lactate dehydrogenase A(LDHA),pyruvate dehydrogenase kinase 1(PDK1)and PFKFB3]in primary cardiomyocytes of each group were measured.RESULTS Compared with the control group,the surface area of primary cardiomyocytes and protein synthesis were significantly increased,the content of FFA,protein and mRNA expressions of HIF-1α,LDHA,PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group,while the contents of CoA and acetyl-CoA,the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated(P＜0.05).Compared with the AngⅡ group,both TSG group and PFK-015 group showed significant improvements in these indexes,with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone(P＜0.05).CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes,decrease protein synthesis,and inhibit their hypertrophic changes.These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.

OBJECTIVE To explore the mechanism of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction. METHODS The rat model of heart failure after myocardial infarction was established by ligation of anterior descending branch of left coronary artery， which was divided into 8 groups： sham operation group， model group， A779 group （1 mg/kg）， A779 （1 mg/kg）+Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， A779 （1 mg/kg） +Tingli dazao xiefei decoction high-dose group （1.6 g/kg）， Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， Tingli dazao xiefei decoction high-dose group （1.6 g/kg） and losartan potassium group （10 mg/kg）. Each group was given equal volume of distilled water or corresponding drugs intragastrically for 4 weeks. Masson staining was used to determine the distribution of collagen fibers in rat myocardium. The content of hydroxyproline （Hyp） in myocardium was determined by alkaline hydrolyzation. The expressions of type Ⅰ and Ⅲ collagen （COLⅠ， COLⅢ）in myocardium were detected by immunohisto-chemistry. Myocardial fibrosis-related indexes such as matrix metalloproteinase-2 （MMP-2）， MMP-9， tissue inhibitor of metalloproteinase-1 （TIMP-1） and soluble suppression of tumorigenicity-2 （sST-2） were detected by ELISA. The protein expressions of angiotensin converting enzyme 2-angiotensin-（1-7）-Mas [ACE2-Ang-（1-7）-Mas] axis were detected by Western blot. RESULTS Compared with sham operation group， myocardial cells in model group and A779 group were disordered， collagen fiber deposition was significantly increased and myocardial fibrosis was obvious； the Hyp content and MMP-2， MMP-9， sST-2 levels were increased， and COL Ⅰ and COL Ⅲ positive expressions were significantly enhanced； TIMP-1 level， protein expressions of ACE2， Ang-（1-7） and Mas were significantly decreased （P＜0.05）. Compared with model group， above indexes of Tingli dazao xiefei decoction equivalent-dose and high-dose groups were improved to different extents. Compared with A779 group， A779+Tingli dazao xiefei decoction equivalent-dose and A779+high-dose groups could improve myocardial arrangement and collagen distribution， reduce the Hyp content and MMP-2， MMP-9 levels， reduce positive expressions of COL Ⅰ and COL Ⅲ （P＜0.05）， but couldn’t improve Ang-（1-7） and Mas protein expression. CONCLUSIONS Tingli dazao xiefei decoction can improve ventricular remodeling in myocardial failure model rats after myocardial infarction by improving the expression of ACE2- Ang（- 1-7）-Mas axis proteins.

Objective: To analyze clinical features and electroneuromyography (ENMG) results of chronic mild occupational carbon disulfide poisoning cases. Methods: A total of 344 patients diagnosed with chronic mild occupational carbon disulfide poisoning based on GBZ 4-2002 Diagnostic Criteria of Occupational Chronic Carbon Disulfide Poisoning were selected as study subjects from 2006 to 2019 using the retrospective study method. Their clinical data was collected and analyzed. Results: The main symptoms of the study subjects were dizziness, headache, insomnia, dreaming, memory impairment, numbness and weakness in the distal extremities. Positive signs mainly included symmetrical glove and stocking distribution like sensory disorders in the distal extremities, and the weakening or absent Achilles tendon reflex and knee reflex. The incidence of symptoms and signs increased with the length of service (all P<0.01). The incidence of fundus and venous changes in patients was 41.3%, which increased with the length of service (P<0.01). ENMG examination showed varying degrees of abnormalities in the peripheral motor and/or sensory nerves in all patients, with a higher incidence of motor nerve abnormalities than sensory nerve abnormalities (21.1% vs 3.7%, P<0.01). The incidence of motor nerve abnormality was higher on the right side than the left side (23.7% vs 18.5%, P<0.01). The incidences of motor nerve abnormalities from high to low in the order were median nerve, common peroneal nerve, ulnar nerve and posterior tibial nerve (34.9% vs 27.9% vs 16.6% vs 5.1%, P<0.01). The incidences of sensory nerve abnormalities from high to low in the order were median nerve, ulnar nerve and sural nerve (5.2% vs 5.1% vs 0.7%, P<0.01). The incidences of left ulnar nerve, right ulnar nerve and right median nerve were higher in male patients than in female patients (15.2% vs 5.3%, 24.0% vs 11.7%, 44.8% vs 28.7%, all P<0.05), while the incidences of the left and right common peroneal nerve in lower extremity motor nerve were lower in male patients than in female patients (18.4% vs 52.1%, 21.2% vs 46.8%, all P<0.01). Conclusion: Chronic mild occupational carbon disulfide poisoning was mainly manifested as multiple peripheral nerve injury. ENMG results showed that the distal motor nerve conduction abnormalities were more sensitive than the sensory nerve conduction abnormalities, with a higher degree of impairment in the upper limb than the lower limb, and more impairment in the right side than the left side.

Prevotella copri and its related taxa are widely detected in mammalian gut microbiomes and have been linked with an enterotype in humans.However,their microevolution and macroevolution among hosts are poorly characterized.In this study,extensively collected marker genes and genomes were analyzed to trace their evolutionary history,host specificity,and biogeographic distribution.Investigations based on marker genes and genomes suggest that a P.copri-containing lineage(PCL)harbors diverse species in higher primates.Firstly,P.copri in the human gut consisted of multiple groups exhibiting high genomic divergence and conspicuous but non-strict biogeographic patterns.Most African strains with high genomic divergence from other strains were phylogenetically located at the root of the species,indicating the co-evolutionary his-tory of P.copri and Homo sapiens.Secondly,although long-term co-evolution between PCL and higher primates was revealed,sporadic signals of co-speciation and extensive host jumping of PCL members were suggested among higher primates.Metagenomic and phylogenetic analyses indicated that P.copri and other PCL species found in domesticated mammals had been recently transmitted from humans.Thirdly,strong evidence was found on the extensively horizontal transfer of genes(e.g.,genes encoding carbohydrate-active enzymes)among sympatric P.copri groups and PCL species in the same primate host.Our study provides panoramic insights into the combined effects of vertical and horizontal transmission,as well as potential niche adaptation,on the microevolutionary and macroevolutionary history for an enterotype-representative lineage.