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.

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.