Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Cibotii Rhizoma has a long history of folk usage and clinical applications,which is commonly used to treat symptoms such as waist and knee soreness,numbness of hands and feet.Its chemical components mainly include sugars and glycosides,aromatics,volatile oils,pterosins,flavonoids,steroids,pyranones,amino acids and inorganic elements.Pharmacological studies have shown that Cibotii Rhizoma has antioxidant,anti-inflammatory,anti-osteoporosis,gastrointestinal protection,antibacterial,liver protection,anticancer,analgesic and other effects.This paper systematically reviews the research status of chemical constituents,pharmacological effects and quality control of Cibotii Rhizoma,which provides reference for the development and rational use of Cibotii Rhizoma.

The concept of "Bo" （搏） originates from The Inner Canon of Yellow Emperor （《黄帝内经》）. Its original meaning mostly refers to gathering and attacking， but in pulseology it reflects the potential of conflict and was widely used in the methods of taking pulse from zang-fu organs and yin and yang. This paper conducted a literature research on the concept and connotation of "Bo" （搏）， and summarized the seven meanings of it， including contention， intersection， stop， change， attachment， pulse， and pathological pulse. At the same time， the pathomechanism of "Bo" （搏） was explained and its four characteristics are summarized， including contention to transformation， concurrent transformation， latent pathogen gathering， and changes transforming to qi； the pathomechanism and locations of "Bo" （搏） were also summarized， including zang-fu organs， channels and collaterals， five body constituents， qi level， blood level， and other aspects， involving therapeutic methods like the opening and diffusing， expressing and tonifying， regulating balance. The concept and connotation of "Bo" （搏） were systematically studied and improved to provide new perspectives and ideas for the diagnosis and treatment of many modern intractable diseases.

Objective: To explore the relationship between adolescent sports participation and aggression, so as to provide a reference basis for sports interventions aimed at reducing adolescent aggression. Methods: The search databases used in the study included China National Knowledge Infrastructure, Vipo, Wanfang, Web of Science, Ebsco, Pro Quest, and PubMed, and the search period was from the construction of the database to October 22, 2023. The search terms for sports participation were "sport" "exercise" "exercise" "physical activity" "physical activity"; the search terms for aggressive behavior were "assault" "aggressive behavior" "aggression"; the search terms for aggressive behavior were "assault" "aggressive behavior" "aggression" "bullying", and "violence", and the above keywords were jointly searched. Foreign language data were searched using Web of Science, Ebsco, Pro Quest, PubMed and supplemented by Google Scholar. The search terms for sports participation were sport, athletics, exercise, train, fitness, physical exercise, physical activity, physical education; and the search terms for aggressive behavior were aggression, bullying, violence, atrocity, fighting, aggressive behavior, physical assault; the above keywords were jointly searched. Statistical analysis was performed using CMA 3.0 software. Results: A total of 20 studies with 80 effect sizes and 9 308 subjects were included. The Metaanalysis showed that adolescent sports participation was moderately negatively correlated with indicators of aggression (r=-0.11), physical aggression (r=-0.14), verbal aggression (r=-0.14), and hostility (r=-0.16), and weakly negatively correlated with indicators of anger (r=-0.08) (P<0.05). Aggressive behavior was influenced by gender, school stage, mode of exercise, and the sports participants region (P<0.05). Conclusions Exercise participation has a positive impact on reducing aggressive behavior in adolescents, and mode of exercise, age, gender, and region are moderating variables in the relationship. Schools can reduce adolescent aggression by developing exercise and physical education interventions.

Objective To optimize the extraction process of total phenolic acids from Cibotii rhizoma using Box-Behnken design-response surface methodology and evaluate antioxidant activity of total phenolic acid in vitro.Methods Taking the liquid-solid ratio,ethanol concentration and extraction temperature as influencing factors,and the extraction rate of total phenolic acids as evaluation indicator,the extraction process of total phenolic acids from Cibotii rhizoma was optimized using a three-factor and three-level Box-Behnken design-response surface methodology on the basis of single factor tests.Meanwhile,the scavenging effects of total phenolic acid extract from Cibotii rhizoma on ABTS·+and DPPH· was determined.Results The optimized extraction process for total phenolic acids from Cibotii rhizoma was as follows:the ethanol concentration of 55％,the extraction temperature of 88℃ and the liquid-solid ratio of 60∶1 mL/g.Under these conditions,the extraction rate could reach 8.67％.When the mass concentration of total phenolic acids extract were 2 mg/mL and 1 mg/mL,the clearance rates of ABTS·+and DPPH·were 92.76％and 88.66％,respectively.Conclusion The theoretical values obtained from the response surface optimization method are consistent with the actual measured values,and the extraction process of total phenolic acids from Cibotii rhizoma was simple and feasible.The total phenolic acids extract from Cibotii rhizoma exhibit strong antioxidant activity in vitro.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis （AIT） mice based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/peroxisome proliferator-activated receptor γ （PPARγ）/glutathione peroxidase 4 （GPX4） pathway. Method120 SPF-grade 7-8-week-old NOD.H-2^h4 mice were randomly divided into control group， model group， low-， medium-， and high-dose Buzhong Yiqitang groups， and western medicine group， with 20 mice in each group. Except for the control group， all mice were fed with classic high-iodine water （0.05% NaI） to induce AIT models after 8 weeks. The low-， medium-， and high-dose Buzhong Yiqitang groups were administered 4.78， 9.56， 19.12 g·kg^-1 of Buzhong Yiqitang， respectively， via gavage. The western medicine group was given 3.033×10^-5 g·kg^-1 selenium yeast tablet suspension via gavage， while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment， samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin （HE） staining，the content of serumantithyroid peroxidase autoantibody（TPOAb）and anti-thyroglobulin antibodies（TGAb）was measured by enzyme-linked immunosorbent assay （ELISA），the kit was used to detect the levels of superoxide dismutase （SOD）， and malondialdehyde （MDA） in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of Nrf2， PPARγ， solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， lysolipid lecithin acyltransferase 3 （LPCAT3）， and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， LPCAT3， and GPX4 proteins in thyroid tissue. ResultCompared with control group， model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue， significantly increased levels of TGAb and TPOAb in serum （P<0.01）， significantly increased MDA levels and decreased SOD levels in serum （P<0.01）， significantly decreased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4 （P<0.01） in thyroid tissue， while the expression of LPCAT3 was significantly increased （P<0.01）. Compared with model group， the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased， significantly decreased levels of TPOAb and TGAb in serum （P<0.05，P<0.01）， decreased MDA levels and increased SOD levels in serum（P<0.05，P<0.01），significantly increased expression of Nrf2， PPARγ， SLC7A11， SLC3A2， and GPX4， while the expression of LPCAT3 was significantly decreased （P<0.05，P<0.01） in the thyroid tissue. Compared with western medication group， Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2， PPARγ， SLC7A11， SLC3A2， GPX4， and LPCAT3 （P<0.05，P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.