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.

Liver disease is a major global health issue, severely impacting patients' quality of life and life expectancy. Integrated Traditional Chinese and Western Medicine demonstrates unique advantages in the field of liver disease treatment. Therefore, this article elaborates on the research progress of integrated traditional Chinese and Western medicine in viral hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, and liver cancer.

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.

Liver disease is a major global health issue, severely impacting patients' quality of life and life expectancy. Integrated Traditional Chinese and Western Medicine demonstrates unique advantages in the field of liver disease treatment. Therefore, this article elaborates on the research progress of integrated traditional Chinese and Western medicine in viral hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, and liver cancer.

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.

Objective:To summarize the efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer.Methods:The clinical data of 28 patients with bladder cancer who were admitted in Zhengzhou People's Hospital from July 2020 to October 2021 were analyzed retrospectively. There were 22 males and 6 females, with the average age of (68.8±8.9) years old. Twenty cases were with single bladder tumor, and 8 cases were with multiple bladder tumors. The diameter of single bladder tumor measured by CT was less than 4 cm, with a median tumor diameter of 2.3(0.9, 2.8)cm. All 28 patients underwent transurethral partial cystectomy combined with intravesical suturation for the first time. Intraoperative intravesical instillation was conducted with 1 g gemcitabine. Bladder hot reperfusion treatment was performed with gemcitabine 2 g at 45℃ immediately after operation. The patients underwent reexamination with cystoscopy every 3 months after operation.Results:All the 28 patients successfully completed the operation. The average operation time was (128.3±16.3)min. No obturator nerve reflection was induced during operation. Muscularis tissue was found in all tumor pathological specimens after operation, among which 4 cases showed muscularis infiltration. Pathology of tumor basal and peripheral tissues showed tumor cell infiltration in 3 cases (1 case full-thickness infiltration, namely the incision margin was positive). The median continuous irrigation time of bladder after operation was 24.0(20.9, 25.0)h. The median time of indwelling catheter after operation was 6.5(6.0, 7.0)days, and one case developed severe bladder spasm. All patients were followed up, with a median follow-up of 7.5(4.0, 10.8) months.Postoperative recurrence occurred in 3 cases, all of which were ectopic recurrence in bladder.The 1-year recurrence rate was 10.7% (3/28).Conclusions:In the first surgical treatment of bladder cancer, transurethral partial cystectomy combined with intravesical suturation can provide accurate pathological staging, and low positive surgical margin rate. Immediate suturation of bladder wound during operation and immediate bladder perfusion chemotherapy can provide short bladder irrigation time, with few adverse reactions and low incidence of complications.

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.

Objective:To compare the accuracy of influenza-like illness (ILI) surveillance by automatic computer analysis based on electronic medical records and by doctor’s report.Methods:A total of 3 542 patients who presented to Yichang Central Hospital fever clinic, respiratory department or emergency department between April to October 2019 with an ICD-10 code for acute respiratory illness (J00-J22) and complete electronic medical information of ILI related syndromes were drawn as the study sample. Taking the classification of the study sample according to the ILI case definition by influenza surveillance professionals as the gold standard, draw the receiver operating characteristic (ROC) curve and calculate sensitivity, specificity, diagnostic consistency to compared the accuracy of ILI surveillance by automatic computer analysis and by doctor's report.Results:Median age of 3 542 cases was 30 (24, 38) years old; 1 179 cases (33.29%) compliance with the case definition, ILI reported by doctors was 1 306 cases (36.87%), and computer automatic identification ILI were 1 150 cases (32.47%); 1 391 (39.27%) cases were men. The results of automatic computer analysis and doctor report consistency of kappa values with gold standard judgment were 0.97 and 0.66 respectively; area under the ROC curve was 0.98 and 0.84, respectively. And the sensitivity and specificity of automatic computer analysis were higher than that of doctor's report (all P values were <0.001), the sensitivity was 96.95% and 82.27%, and the specificity was 99.70% and 85.78%, respectively. Conclusion:The automatic computer analysis based on electronic medical records can identified ILI cases with good sensitivity and specificity in ILI case surveillance.