ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia （OAS） and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group （n=7） and a modeling group （n=28）. The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups： model， Cuscutae Semen-Lycii Fructus granules （3.2 g·kg^-1）， Cuscutae Semen-Lycii Fructus total flavonoids （0.34 g·kg^-1）， and L-carnitine （0.38 g·kg^-1）， and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase （SOD）， malondialdehyde （MAD）， and glutathione peroxidase （GSH-Px） in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels， respectively， of SIRT1， Nrf2， Occludin， zonula occludens-1 （ZO-1）， connexin 43 （CX43）， and β-catenin. ResultsCompared with the blank group， the model group showed decreased total sperm count and motility （P<0.05， P<0.01）， obvious damage in the testicular tissue and blood-testis barrier structure， reduced score of spermatogenic function （P<0.01）， declined levels of GSH-Px and SOD in the testicular tissue （P<0.05）， elevated level of MDA， and down-regulated protein levels of SIRT1， Nrf2， ZO-1， CX43， β-catenin， and occludin （P<0.05， P<0.01） and mRNA levels of SIRT1， Nrf2， ZO-1， CX43， and β-catenin in the testicular tissue （P<0.05， P<0.01）. After treatment， the testicular tissue， blood-testis barrier structure， and score of spermatogenic function （P<0.01） were improved in the Cuscutae Semen-Lycii Fructus granules group， Cuscutae Semen-Lycii Fructus total flavonoids group， and L-carnitine group. Compared with the model group， the treatment groups presented lowered levels of GSH-Px and SOD （P<0.05， P<0.01）， and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1， Nrf2， ZO-1， CX43， β-catenin， and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group （P<0.05， P<0.01）. ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage， thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.

ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia （OAS） and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group （n=7） and a modeling group （n=28）. The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups： model， Cuscutae Semen-Lycii Fructus granules （3.2 g·kg^-1）， Cuscutae Semen-Lycii Fructus total flavonoids （0.34 g·kg^-1）， and L-carnitine （0.38 g·kg^-1）， and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase （SOD）， malondialdehyde （MAD）， and glutathione peroxidase （GSH-Px） in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels， respectively， of SIRT1， Nrf2， Occludin， zonula occludens-1 （ZO-1）， connexin 43 （CX43）， and β-catenin. ResultsCompared with the blank group， the model group showed decreased total sperm count and motility （P<0.05， P<0.01）， obvious damage in the testicular tissue and blood-testis barrier structure， reduced score of spermatogenic function （P<0.01）， declined levels of GSH-Px and SOD in the testicular tissue （P<0.05）， elevated level of MDA， and down-regulated protein levels of SIRT1， Nrf2， ZO-1， CX43， β-catenin， and occludin （P<0.05， P<0.01） and mRNA levels of SIRT1， Nrf2， ZO-1， CX43， and β-catenin in the testicular tissue （P<0.05， P<0.01）. After treatment， the testicular tissue， blood-testis barrier structure， and score of spermatogenic function （P<0.01） were improved in the Cuscutae Semen-Lycii Fructus granules group， Cuscutae Semen-Lycii Fructus total flavonoids group， and L-carnitine group. Compared with the model group， the treatment groups presented lowered levels of GSH-Px and SOD （P<0.05， P<0.01）， and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1， Nrf2， ZO-1， CX43， β-catenin， and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group （P<0.05， P<0.01）. ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage， thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.

Colorectal cancer （CRC） is a prevalent malignant tumor of the digestive tract， with a high incidence and high mortality. The majority of patients are diagnosed at the middle or advanced stage， which severely influences and threatens their physical health. Current treatment modalities such as surgery， radiotherapy， and chemotherapy often encounter challenges including metastasis， recurrence， and drug resistance. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway serves as a classical regulator that regulates physiological processes such as cell cycle， autophagy， apoptosis， and proliferation. Overexpression of this pathway is observed in various tumors. In the context of CRC， the activation of this pathway can facilitate the proliferation， invasion， and migration， inhibit the autophagy and apoptosis， promote the epithelial-mesenchymal transition of CRC cells， enhance angiogenesis within the tumor， and contribute to chemotherapy resistance and radiation resistance in CRC. Traditional Chinese medicine （TCM） treatment can exert an anti-CRC effect by inhibiting this pathway， thereby improving clinical efficacy and safety. This article retrieves relevant research literature published domestically and internationally regarding the regulation of the PI3K/Akt/mTOR signaling pathway by TCM in the treatment of CRC and conducts detailed classification and summary. The active components of TCM include glycosides， flavonoids， alkaloids， terpenoids， polyphenols， and naphthoquinones. The volatile oils and extracts of TCM include Angelicae Sinensis Radix volatile oil， Astragali Radix polysaccharides， Caryophylli Flos extract， Forsythiae Fructus extract， Curcumae Longae Rhizoma extract， and Celastrus orbiculatus extract. The compound formulas of TCM include Banxia Xiexin decoction， Jianpi Qingre Huoxue formula， and Chanling Plaster. Through summary and analysis， it is discovered that the abovementioned TCM can produce effects such as blocking the cell cycle， inducing autophagy and apoptosis， inhibiting angiogenesis， suppressing proliferation and migration， and reversing chemotherapy resistance and radiotherapy resistance by inhibiting the PI3K/Akt/mTOR pathway in CRC cells. TCM holds promise in the research and application of targeting the PI3K/Akt/mTOR signaling pathway for CRC treatment. The summary and conclusion of this article aim to provide references for subsequent research and the development of new drugs.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Objective To summarize the experience of multi-disciplinary team(MDT)in the pediatric department of Qujing Maternal and Child Health Hospital,and to evaluate the effectiveness of MDT on neonatal brain injury.Methods The clinical data of children with brain injury and treated in the pediatrics department of Qujing Maternal and Child Health Hospital from November 2019 to April 2023 were collected.The children with brain injury and treated from October 2019 to June 2020 were regarded as the non-MDT group,and the children with brain injury and treated from July 2020 to April 2023 were regarded as the MDT group for comparative analysis.Chi-square test/t-test was used to compare and analyze the clinical data of the two groups.Results Among the 890 cases of pediatric brain injury,there were 519 males and 371 females.The median and quartiles of the age distribution for the two groups were as follows:MDT group 2.00(0.82,5.00)years and non-MDT group 1.00(1.00,4.00)years.Craniocerebral injury was the main type of brain injury in both groups,in addition,among children with craniocerebral injury and intracranial hemorrhage,the cure rate of MDT group was higher than that of non-MDT group,and the difference was statistically significant(P<0.05).Among the 405 children in MDT group,154(38.0%)underwent the surgery,while among the 485 children in non-MDT group,121(24.9%)underwent the surgery.The difference was statistically significant(P<0.05).23.2% of children in MDT group were in critical condition during the hospitalization,which was significantly lower than that in non-MDT group(30.5%),and the difference was statistically significant(P<0.05).The unhealed rate of MDT group(2.0%)was also significantly lower than that of non-MDT group(5.6%),the cure rate of MDT group(40.5%)was significantly higher than that of non-MDT group(34.4%),and there was a statistically significant difference(P<0.05).The expense of treatment,medicine and sanitary materials in MDT group were lower than those in non-MDT group,and the differences were statistically significant(P<0.05).The multivariate Logistic regression model analysis of the cure rate of children with brain injury showed that the MDT model could effectively improve the cure rate of children with brain injury(RR = 1.513,95% CI = 1.134-2.020).The results of multiple linear regression model analysis showed that there was no statistical difference in the effect of MDT on the actual hospitalization days of children(P>0.05).Conclusion Using MDT model to diagnose and treat children with brain injury is helpful to improve the cure rate,reduce the risk of children's disease aggravation,and achieve the significant therapeutic effects in children with brain injury.MDT model is worth popularizing and applying in children with brain injury.

Objective:To explore the relationship between risk perception and health promoting lifestyle profile in population with cardiovascular disease (CVD), and construct a prediction model for clinical screening and targeted intervention.Methods:A cross-sectional survey method was used to select 272 people at moderate and high risk of CVD from the Second Affiliated Hospital of Zhejiang University School of Medicine from March to August 2022. The general information questionnaire, Chinese version of Attitude and Beliefs about Cardiovascular Disease Knowledge and Risk Questionnaire (ABCD-C), and Health Promoting Lifestyle Profile-II (HPLP Ⅱ) were used. Based on multiple regression analysis, a nomogram model for health promoting lifestyle in high-risk CVD population was constructed.Results:Among 272 participants, male 150 cases, female 122 cases, aged (60.58 ± 10.64) years old. The total ABCD-C score was (56.57 ± 5.69), and the total HPLP Ⅱ score was (111.92 ± 12.47). ABCD-C score was significantly positively correlated with HPLP Ⅱ score ( r=0.556, P<0.01). The median of HPLP Ⅱ total score (111 points) was used as the cut-off point for low level of health-promoting lifestyle (≤111 points) and high level of health-promoting lifestyle (>111 points), and used it as the dependent variable, smoking ( OR=0.215, 95% CI 0.104-0.446) was a barrier factor for participants to adopt healthy lifestyle; being married ( OR=14.237, 95% CI 1.963-103.238), having a family average monthly income higher than 5 000 yuan ( OR=4.101, 95% CI 1.369-12.288), higher score of CVD prevention knowledge ( OR=1.660, 95% CI 1.373-2.007), perceived benefits and intention to change physical activity ( OR=1.445, 95% CI 1.255-1.663), perceived benefits and intention to change healthy diet ( OR=1.322, 95% CI 1.058-1.654) were promoting factors. Conclusions:The health-promoting lifestyle of populations at risk for CVD is above-average, influenced by factors such as smoking, marital and economic status, risk attitudes, and beliefs. Utilizing the nomogram model for early screening and targeted risk communication among key populations may contribute to improving their health behavior.