Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

Thyroid cancer is caused by multiple factors, including genetics, environment, metabolism, and the immune microenvironment, among which ionizing radiation exposure is an important risk factor for thyroid cancer. As one of the most sensitive target organs of ionizing radiation, the thyroid gland may have different risks of thyroid cancer caused by different types of ionizing radiation exposures, such as medical exposure, occupational exposure, and emergency exposure. The sensitivity of children and adolescents are higher than that of adults. The dose-response relationship still needs to be further explored. The molecular mechanism between ionizing radiation and the increased risk of thyroid cancer is complex, which may involve DNA damage and repair abnormalities, gene mutations, non-coding RNA regulation, DNA methylation, cell cycle regulation imbalance, and immune microenvironment changes. This article reviews the risk and molecular mechanisms associated with different types of ionizing radiation exposure in thyroid cancer, based on literature retrieved from CNKI and PubMed databases. It aims to provide a theoretical basis for the early monitoring, prevention, and intervention of thyroid cancer related to ionizing radiation exposure.

OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

Objective:To investigate the expression of N6-methyladenosine(m6A)reader heterogeneous nuclear ribonucleoprotein A2/B1(hnRNPA2B1)in human gastric cancer(GC)tissue and its effect on the proliferation and invasion of MKN-28 cells.Methods:The Cancer Genome Atlas and Gene Expression Omnibus were used to analyze the expression of hnRNPA2B1 and long noncoding RNA(ln-cRNA)mir-100-let-7a-2-mir-125b-1 cluster host gene(MIR100HG)in GC tissue and their association with the clinical prognosis of patients with GC.Quantitative PCR and Western blotting were used to measure the effect of hnRNPA2B1 on the expression level of MIR100HG and its downstream Wnt/β-catenin signaling pathway;Methylated RNA immunoprecipitation(MeRIP)was used to mea-sure the m6A level of MIR100HG;CCK-8 assay and Transwell assay were used to observe cell proliferation and invasion.Results:Com-pared with paracancerous tissue,human GC tissue showed significant increases in the expression levels of hnRNPA2B1(t=6.101,P<0.001)and MIR100HG(t=2.191,P=0.036 7),and the high expression levels of hnRNPA2B1 and MIR100HG were associated with poor survival in patients with GC.Knockdown of hnRNPA2B1 reduced the mRNA expression level(t=5.156,P=0.007)and m6A level of MIR100HG(t=4.789,P=0.010),inhibited the proliferation and invasion of MKN-28 cells(t=4.915,P=0.008 and t=5.167,P=0.007),and blocked the activity of the Wnt/β-catenin signaling pathway(P<0.05).Overexpression of MIR100HG promoted cell pro-liferation and invasion(t=3.578,P=0.023 and t=8.411,P=0.001),activated the Wnt/β-catenin signaling pathway(P<0.01),and re-versed the antitumor effect induced by hnRNPA2B1 knockdown(t=3.667,P=0.021).Conclusion:This study shows that hnRNPA2B1-mediated m6A modification of MIR100HG promotes the proliferation and invasion of GC MKN-28 cells by activating the Wnt/β-catenin signaling pathway.

Objective To investigate the clinical efficacy of Yiqi Huoxue Prescription(derived from Shengyu Decoction)in the treatment of mild cervical spondylotic myelopathy(CSM)with qi deficiency and blood stasis type.Methods A total of 128 patients with mild CSM of qi deficiency and blood stasis type who admitted to Guangdong Provincial Hospital of Chinese Medicine from January 2022 to January 2024 were randomly divided into the control group and the trial group according to the random number table method,with 64 cases in each group.The control group was treated with oral administration of Mecobalamin Tablets,and the trial group was treated with Yiqi Huoxue Prescription orally on the basis of treatment for the control group.The two groups were all treated for four weeks,and then were followed up for three months after the completion of treatment.The CSM scores of the Japanese Orthopedic Association(JOA)and the traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before treatment,after two weeks of treatment,after four weeks of treatment,and three months after the completion of treatment.And then the clinical efficacy,progression of CSM and the incidence of adverse reactions of the two groups were evaluated.Results(1)During the trial,two cases in the control group and three cases in the trial group fell off,and eventually a total of 123 cases were included,62 cases in the control group and 61 cases in the trial group.(2)Three months after the completion of treatment,the total effective rate of the trial group was 93.44%(57/61)and that of the control group was 82.26%(51/62),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the trial group was significantly superior to that of the control group,the difference being statistically significant(P<0.05).(3)After two and four weeks of treatment as well as three months after the completion of treatment,JOA scores in the two groups were increased compared with those before treatment(P<0.05),and JOA scores of the trial group at various time points mentioned above were higher than those of the control group,the difference being statistically significant(P<0.05).(4)After two and four weeks of treatment as well as three months after the completion of treatment,TCM syndrome scores in the two groups were decreased compared with those before treatment(P<0.05),and TCM syndrome scores of the trial group at various time points mentioned above were lower than those of the control group,the difference being statistically significant(P<0.05).(5)During the follow-up period,there was none case of significant aggravation or progression to moderate-severe illness in the two groups,and there were no adverse events such as allergies and gastrointestinal reactions.Conclusion Yiqi Huoxue Prescription exerts certain efficacy in treating patients with mild CSM of the qi deficiency and blood stasis type,and the treatment method is effective on improving the spinal cord function and symptoms of qi deficiency and blood stasis type,and slowing down the progression of disease in the patients,with high safety.

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

OBJECTIVE To establish a clinical pharmaceutical pathway of anti-infective therapy for high-risk populations of antibiotic-associated encephalopathy （AAE）， and analyze its application effects. METHODS Clinical pharmacists developed the “AAE High-Risk Population Screening Form” and “Antibiotic AAE Risk Comparison Form” based on literature and expert opinions， and established the “Clinical Pharmaceutical Pathway of Anti-infective Treatment for AAE High-Risk Population” in our hospital. A prospective， non-randomized controlled study was conducted from May 2023 to April 2024， including 50 cases in the observation group and 50 cases in the control group among patients with pulmonary infections admitted to the Dept. of Internal Medicine in our hospital. The observation group was involved in the development of an anti-infective treatment following the clinical pharmaceutical pathway by clinical pharmacists， while the control group received routine anti-infective treatment by clinical physicians. The occurrence of AAE， the rational antibiotic drug use， and the effectiveness of initial anti-infective treatment in the two groups were observed， and the intervention measures and outcomes of AAE cases were summarized. RESULTS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population was preliminarily established in our hospital. The analysis of the application effects showed that there was 1 case of AAE in the observation group and 8 cases in the control group， with a significantly lower incidence of AAE in the observation group than in the control group； the rational antibiotic drug use and the effectiveness of initial anti-infective treatment in the observation group were both significantly superior to those in the control group （P＜0.05）. Drug withdrawal and dressing change were the preferred effective intervention measures for AAE， and encephalopathy treatment drugs could be used as auxiliary measures for symptom relief. Timely and effective intervention was conducive to rapid symptom relief， with a total improvement rate of AAE of 88.89%. CONCLUSIONS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population can effectively prevent the occurrence of AAE as well as contribute to promoting rational drug use and the effectiveness of initial anti-infection plans and strengthening treatment outcomes.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

BACKGROUND:Pain mechanisms in patients with lumbar disc herniation are associated with inflammation,autophagy is closely related to intervertebral disc diseases and inflammatory response,and aberrant miR-206 expression can trigger skeletal diseases. OBJECTIVE:To investigate the mechanism of miR-206 on inflammation,analgesia and autophagy related proteins in nucleus pulposus in rats with lumbar disc herniation. METHODS:Sixty SPF male Sprague-Dawley rats were randomly divided into control group,model group,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group.Animal models of lumbar disc herniation were established except for the control group.Ten days after modeling,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group were injected with miR-206 mimics-NC(20 μmol/L,10 μL),miR-206 mimics(20 μmol/L,10 μL),miR-206 inhibitor-NC(20 μmol/L,10 μL)and miR-206 inhibitor(20 μmol/L,10 μL),respectively.Administration was given once a day for 4 continuous days.The control group and model group were injected with the same dose of normal saline.The paw withdrawal mechanical threshold of bilateral hind feet was measured by Von Frey filaments,and the paw withdrawal thermal latency of bilateral hind feet was measured by heat pain tester.The morphology of dorsal root ganglia was observed by hematoxylin-eosin staining.The expressions of inflammatory factors phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,and interleukin 1β in nucleus pulposus were detected by qPCR.The expressions of autophagy-related proteins LC3I and Beclin-1 were detected by western blot assay. RESULTS AND CONCLUSION:At 3,7,and 14 days after modeling,the paw withdrawal mechanical threshold and paw withdrawal thermal latency were both decreased in the model group compared with the control group,while the levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I and Beclin-1 increased(P<0.05).The above indexes showed no significant changes in the miR-206 inhibitor-NC group and miR-206 mimics-NC group compared with the model group(P>0.05).Compared with the miR-206 mimics-NC group,the miR-206 mimics group had lower paw withdrawal mechanical threshold and paw withdrawal thermal latency and higher levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I,and Beclin-1 levels(P<0.05).Compared with the miR-206 inhibitor-NC group,the rats in the miR-206 inhibitor group showed opposite changes in the above indicators,and there were significant differences between the two groups(P<0.05).To conclude,inhibition of miR-206 can significantly improve the level of inflammatory factors in nucleus pulposus of rats with lumbar disc herniation,increase pain threshold,and reduce autophagy.The mechanism is related to the inhibition of LC3I and Beclin-1 expression.