Objective To explore scientific and accurate prediction methods for the incidence of hand, foot, and mouth disease in the post-pandemic era, and to address modeling challenges caused by abnormal fluctuations in case numbers from 2020 to 2023. Methods The seasonal index was used to pre-process the data. The traditional seasonal autoregressive integrated moving average (SARIMA) model, singular spectrum analysis (SSA)-ARIMA model, ARIMA-Long short-term memory (LSTM) model, and SSA-ARIMA-LSTM model were used to fit the incidence from 2013 to 2023, and the incidence of hand, foot and mouth disease in 2024 was predicted. The real data collected in 2024 were used as the test set to compare the prediction performance of the models. Results The fitting performance of the constructed models was as follows: the ARIMA model had MAE=107.50 and RMSE=144.53, the SSA-ARIMA model showed MAE=2.84 and RMSE=4.33, the ARIMA-LSTM model achieved MAE=99.46 and RMSE=131.59, and the SSA-ARIMA-LSTM model had MAE=96.35 and RMSE=132.13. In terms of prediction performance, the ARIMA model resulted in MAE=151.64 and RMSE=146.70, the SSA-ARIMA model demonstrated MAE=41.22 and RMSE=57.01, the ARIMA-LSTM model yielded MAE=220.75 and RMSE=257.89, and the SSA-ARIMA-LSTM model recorded MAE=58.83 and RMSE=72.06. Conclusion The SSA-ARIMA model has the best fitting degree and the highest prediction accuracy, and is suitable for predicting the incidence trend of hand, foot and mouth disease.

Objective:ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms.Methods:A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results:An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group ( P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues ( P＜0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival ( P＜0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients ( P=6.4e-14). Conclusions:ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Objective To explore the compatibility law of amenorrhea and commonly used local herbs in southwest China using hypergraph;To provide drug choice for the clinical treatment of modern TCM amenorrhea and promote the development and utilization of local Chinese materia medica resources.Methods In this study,the data of prescriptions for the treatment of amenorrhea in Southwest China were used as the data source.By constructing formulas related to amenorrhea-hypergraph(AFR-HG),the topological structure of AFR-HG was analyzed,and the core subnet was extracted according to the node weighted hypercentrality.Based on the sub-network AFR-HG-p1 extracted from the top 20 kinds of Chinese materia medica in AFR-HG,the Kumar algorithm was used to divide the efficacy community network.Results A total of 123 amenorrhea prescriptions were included in this study.Angelicae Sinensis Radix,Carthami Flos,Cyperi Rhizoma,Chuanxiong Rhizoma and other drugs with the efficacy of promoting blood circulation and removing blood stasis,soothing liver and regulating qi,and warming and tonifying were the main drugs with high frequency.Three layers of core subnets were extracted layer by layer through weighted hyper-centrality sorting.The first layer contained Angelicae Sinensis Radix,Chuanxiong Rhizoma,Hyperici Sampsonii Herba,etc.;the second layer of drugs were mainly Lycopi Herba,Rubiae Radix et Rhizoma,Bombycis Feculae,etc.;the third layer of drugs were mainly Ginseng Radix et Rhizoma Rubra,Moutan Cortex,Sargentodoxae Caulis and other drugs;based on the top 20 node overdose drugs,community drugs were obtained through community detection:the first community subnet was Armeniacae Semen Amarum,Draconis Sanguis,Corydalis Rhizoma,etc.,the second community subnet was Rubiae Radix et Rhizoma,Rosae Chinensis Flos,Hyperici Sampsonii Herba,etc.,and the third community subnet was Akebiae Caulis,Homalomenae Rhizoma,Bombycis Feculae,etc.Conclusion In prescriptions of amenorrhea in Southwest China,the treatment principles are basically consistent with modern clinical practice.In addition to commonly used drugs,local herbal medicines and similar medicines are also common.It is of great value to explore the rules of prescriptions for the development and utilization of Chinese materia medica resources.

OBJECTIVE To explore the potential mechanisms and bioactive compounds of licorice against COVID-19 based on a multidimensional interaction of"component-disease-symptom-target".METHODS Firstly,candidate target sets for licorice compo-nents were obtained from the ETCM2.0 database based on the Encyclopedia of Traditional Chinese Medicine,and the disease symp-toms and associated target sets for COVID-19 were derived from the GeneCards and HPO databases.And then a protein interaction network was constructed using the String database(version 12.0).By calculating topological eigenvalues and functional enrichment analysis,the potential mechanisms of action were explored.Combined with Schr?dinger molecular docking virtual screening,candidate pharmacodynamic substances were identified.Fluorescence resonance energy transfer was used for experimental verification.RESULTS Licorice might improve symptoms of COVID-19(fever,chest pain and so on)by regulating the imbalance of"immune-inflammation"network and signal transduction abnormalities during the development and progress of COVID-19,such as coronavirus disease-COVID-19,Toll-like receptor signaling pathway and NOD-like receptor signaling pathway.The components,such as Isos-chaftoside and Hesperidin,were identified to possess high binding affinity with the critical enzymes for viral replication.Isoschaftoside,Hesperidin,Isoliquiritin apioside and Vicenin-2 exhibited varying degrees of inhibition on the enzyme of 3CLpro at different concentra-tions while excluding the interference of the compounds' fluorescence.CONCLUSION Through experimental verification using a multidimensional interaction network of"component-disease-symptom-target",the key pharmacologically active substances of licorice in the fight against COVID-19 are preliminarily identified,and their mechanism of action through overall regulation is elucidated.

OBJECTIVE To explore the potential mechanisms and bioactive compounds of licorice against COVID-19 based on a multidimensional interaction of"component-disease-symptom-target".METHODS Firstly,candidate target sets for licorice compo-nents were obtained from the ETCM2.0 database based on the Encyclopedia of Traditional Chinese Medicine,and the disease symp-toms and associated target sets for COVID-19 were derived from the GeneCards and HPO databases.And then a protein interaction network was constructed using the String database(version 12.0).By calculating topological eigenvalues and functional enrichment analysis,the potential mechanisms of action were explored.Combined with Schr?dinger molecular docking virtual screening,candidate pharmacodynamic substances were identified.Fluorescence resonance energy transfer was used for experimental verification.RESULTS Licorice might improve symptoms of COVID-19(fever,chest pain and so on)by regulating the imbalance of"immune-inflammation"network and signal transduction abnormalities during the development and progress of COVID-19,such as coronavirus disease-COVID-19,Toll-like receptor signaling pathway and NOD-like receptor signaling pathway.The components,such as Isos-chaftoside and Hesperidin,were identified to possess high binding affinity with the critical enzymes for viral replication.Isoschaftoside,Hesperidin,Isoliquiritin apioside and Vicenin-2 exhibited varying degrees of inhibition on the enzyme of 3CLpro at different concentra-tions while excluding the interference of the compounds' fluorescence.CONCLUSION Through experimental verification using a multidimensional interaction network of"component-disease-symptom-target",the key pharmacologically active substances of licorice in the fight against COVID-19 are preliminarily identified,and their mechanism of action through overall regulation is elucidated.

Objective To explore the compatibility law of amenorrhea and commonly used local herbs in southwest China using hypergraph;To provide drug choice for the clinical treatment of modern TCM amenorrhea and promote the development and utilization of local Chinese materia medica resources.Methods In this study,the data of prescriptions for the treatment of amenorrhea in Southwest China were used as the data source.By constructing formulas related to amenorrhea-hypergraph(AFR-HG),the topological structure of AFR-HG was analyzed,and the core subnet was extracted according to the node weighted hypercentrality.Based on the sub-network AFR-HG-p1 extracted from the top 20 kinds of Chinese materia medica in AFR-HG,the Kumar algorithm was used to divide the efficacy community network.Results A total of 123 amenorrhea prescriptions were included in this study.Angelicae Sinensis Radix,Carthami Flos,Cyperi Rhizoma,Chuanxiong Rhizoma and other drugs with the efficacy of promoting blood circulation and removing blood stasis,soothing liver and regulating qi,and warming and tonifying were the main drugs with high frequency.Three layers of core subnets were extracted layer by layer through weighted hyper-centrality sorting.The first layer contained Angelicae Sinensis Radix,Chuanxiong Rhizoma,Hyperici Sampsonii Herba,etc.;the second layer of drugs were mainly Lycopi Herba,Rubiae Radix et Rhizoma,Bombycis Feculae,etc.;the third layer of drugs were mainly Ginseng Radix et Rhizoma Rubra,Moutan Cortex,Sargentodoxae Caulis and other drugs;based on the top 20 node overdose drugs,community drugs were obtained through community detection:the first community subnet was Armeniacae Semen Amarum,Draconis Sanguis,Corydalis Rhizoma,etc.,the second community subnet was Rubiae Radix et Rhizoma,Rosae Chinensis Flos,Hyperici Sampsonii Herba,etc.,and the third community subnet was Akebiae Caulis,Homalomenae Rhizoma,Bombycis Feculae,etc.Conclusion In prescriptions of amenorrhea in Southwest China,the treatment principles are basically consistent with modern clinical practice.In addition to commonly used drugs,local herbal medicines and similar medicines are also common.It is of great value to explore the rules of prescriptions for the development and utilization of Chinese materia medica resources.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Objective:ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms.Methods:A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results:An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group ( P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues ( P＜0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival ( P＜0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients ( P=6.4e-14). Conclusions:ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.

ObjectiveTo systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene". MethodPutative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot. ResultA total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）. ConclusionHBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.