Objective:To explore the application value of high-resolution temporal bone CT and DW-MRI fusion technology in achieving precise diagnosis and anatomical localization of middle ear cholesteatoma during endoscopic surgery. Methods:Eighteen patients initially diagnosed with middle ear cholesteatoma in the Department of Otolaryngology Head and Neck Surgery, Shaanxi Provincial People's Hospital, from January to June 2024 were enrolled.Preoperative high-resolution temporal bone CT and DW-MRI were performed, and rtStation software was used for image fusion to construct CT-MRI fused images. The involvement of cholesteatoma in six anatomical subregions of the temporal bone was evaluated. Using surgical pathology as the gold standard, and combining surgical videos and anatomical records, the sensitivity, specificity, and accuracy of pure CT, pure DW-MRI, and CT-MRI fused images in evaluating middle ear cholesteatoma lesions were compared. Results:A total of 18 patients were included, and 17 cases were pathologically confirmed as middle ear cholesteatoma postoperatively. The sensitivity of the preoperative of preoperative CT was 100%, but the specificity was only 44.44%, with an overall accuracy of 72.22%; the sensitivity and specificity of DW-MRI evaluation were 81.46% and 85.19%, the accuracy was 83.33%, respectively. In contrast, the sensitivity and specificity of CT-MRI fusion image to the spatial localization of cholesteatoma were higher than that of DW-MRI alone（92.59% vs 81.46%; 98.15% vs 85.19%）, and the diagnostic accuracy was also significantly improved（95.37% vs 83.33%）. The Kappa values for the agreement between HRCT, DW-MRI, and CT-MRI segmentation localization and pathological results were 0.444, 0.667, and 0.907 respectively. The chi-square paired t-test confirmed statistically significant diagnostic differences between groups（P<0.001）. Results demonstrated that CT-MRI significantly outperformed HRCT and DW-MRI in diagnostic efficacy for segmental localization of primary posterior congenital middle ear cholesteatoma. Conclusion:High-resolution temporal bone CT combined with DW-MRI fusion technology demonstrates higher sensitivity, specificity, and accuracy in the diagnosis and spatial localization of middle ear cholesteatoma than single imaging modalities. It can provide more precise evaluation of lesion scope for endoscopic surgery, showing important clinical application value.
Humans ; Cholesteatoma, Middle Ear/diagnostic imaging* ; Tomography, X-Ray Computed ; Temporal Bone/diagnostic imaging* ; Diffusion Magnetic Resonance Imaging ; Female ; Male ; Adult ; Sensitivity and Specificity ; Middle Aged ; Endoscopy

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.

Cancer is a prevalent and challenging disease that is difficult to treat.Western medicine recognizes the disruption of the immune and inflammatory microenvironment as a crucial factor in the development and progression of cancer.According to traditional Chinese medicine,cancer falls into the categories of"accumulation"and"abnormal masses".Based on the attributes of cold and heat in the overall and local conditions as well as the characteristic of the struggle between the vital qi and pathogenic factors at different stages of this disease,this article proposes the concept of"body coldness and tumor heat"to describe the pathogenesis of cancer formation and progression.This pathogenesis aligns with the disruption of the immune and inflammatory microenvironment in modern medical oncology.The article suggests a treatment approach that focuses on balancing cold and heat,nourishing and protecting yang qi,warming the kidneys,and strengthening the spleen to address the"coldness of the entire body".This approach also involves promoting qi circulation,eliminating dampness,phlegm,and stasis,and detoxifying and dispersing nodules to address the"heat in the tumor locally".By addressing deficiencies,eliminating pathogenic factors,and promoting circulation to alleviate stagnation,the aim is to restore the balance of yin and yang and improve the complex state of"coldness of the entire body"and"heat in the tumor locally".These interventions can ameliorate the disorder in the microenvironment and enhance clinical efficacy.

The clinical data, laboratory test, and gene mutations were collected from a family with pseudohypoaldosteronism type II(PHA2). The proband, aged 1 year and 7 months, presented with hyperkalemia(6.69 mmol/L; reference range 3.5-5.3 mmol/L), blood pressure of 110/68 mmHg(normal<106/61 mmHg, 1 mmHg=0.133 kPa), blood chloride of 111.5 mmol/L(reference 99-110 mmol/L), blood HCO 3- of 17.1 mmol/L(reference 22-29 mmol/L), estimated glomerular filtration rate of 128.5 mL·min -1·(1.73 m 2) -1[>90 mL·min -1·(1.73 m 2) -1], and blood renin concentration of 0.30 μIU/mL(reference 4.2-45.6 μIU/mL). The mother and maternal grandfather also exhibited normal renal function with hyperkalemia, hypertension, hyperchloremia, metabolic acidosis, and low renin. Genetic testing revealed a heterozygous missense mutation(c.1685A>G, p. E562G) in exon 7 of the no-lysine kinase 4(WNK4) gene. Treatment with hydrochlorothiazide was effective. Literature review comparing this E562G pedigree with other WNK4 variants suggested clinical heterogeneity of WNK4 mutations. For unexplained hyperkalemia, especially with concurrent hypertension, PHA2 should be considered early for genetic screening to prevent misdiagnosis or delayed diagnosis.

Objective:To analyze the clinical characteristics of a case of CNNM2 gene heterozygous mutation causing hypomagnesemia epilepsy mental retardation (HOMGSMR1) [MIM: 616418] in a child, and explore the association between genotype and phenotype.Methods:We followed up and retrospectively analyzed the clinical characteristics of a case of HOMGSMR1 caused by CNNM2 gene heterozygous mutation treated at Maternal and Child Health Care Hospital of Liuyang. Through whole exome sequencing of the family and bioinformatics analysis of the original data, we consulted databases and literature materials such as Online Mendelian Inheritance in Man (OMIM), ClinVar, gnomAD, GeneReviews, Pubmed, and China National Knowledge Infrastructure (CNKI), The American College of Medical Genetics and Genomics (ACMG) guidelines were used to rate heterozygous deletion mutations in the locked CNNM2 gene.Results:Patient, male, 3 months and 18 days old, mother gave birth to 1 child with 1 pregnancy, recurrent convulsions for more than 10 days, and multiple tests showed that blood magnesium levels were below normal, fluctuating between 0.51-0.55 mmol/L; After oral administration of " oxcarbazepine" and " magnesium sulfate", convulsions improved and blood magnesium concentration increased, but remained below normal, with the highest being 0.61 mmol/L. The sequencing results of the whole exome display of the family showed that the child carried a heterozygous deletion mutation in the exon region of the CNNM2 gene (c.838_843delATGGCCp. M280-A281del), which was not detected in their parents, indicating a new mutation. The large-scale population frequency database gnomAD did not include this mutation, and no literature reported this mutation. According to the ACMG guidelines, it was rated as a suspected pathogenic variant. The pathogenic variation of this gene can lead to autosomal dominant HOMGSMR1, which was consistent with genetic patterns.Conclusions:CNNM2 gene c. 838_ 843delATGGCC (p.M280_A281del) is a suspected pathogenic variant in this patient, with genotype and phenotype matching and heterozygous mutations following genetic patterns. Autosomal dominant inheritance is the molecular cause of clinical manifestations in this patient, and it is an unreported novel mutation.

Objective: To study the diagnostic accuracy and the distance between the root of maxillary posterior tooth and the maxillary sinus using panoramic radiography and cone beam computer tomography; to provide basic information for clinicians to treat diseases in the maxillary posterior region. Methods: Eighty patients were included in this study. A total of 671 specimens were measured for the distance between the root tip and the maxillary sinus floor in both imaging modalities. Results : The roots that did not contact the sinus floor or contacted but did not project into the sinus cavity showed an agreement of 82% and 70% when using panoramic radiography. Forty-eight percent of the roots that projected into the sinus cavity in panoramic radiography showed protrusion into the sinus with cone beam computer tomography (CBCT). For panoramic radiography and CBCT showing root projections into the sinus cavity, the average distances were 2.19 ± 1.82 mm and 1.47 ± 1.01 mm, respectively. There was a significant difference between the two values (P ＜ 0.05). Conclusion Panoramic radiography is more accurate when roots of maxillary posterior teeth do not contact the sinus floor or contact it. However, it has a lower accuracy rate when the tooth roots protrude into the sinus.

OBJECTIVE：To isolate and purify baicalin metabolites from rat bile ，and to study its effect on the proliferation of liver cancer HepG 2 cells. METHODS ：Totally of 6 SD rats were collected ，anesthetized and then intubated with bile ducts. They were given baicalin （168 mg/kg）intragastrically after the rats were awake as well as the bile sample 1 was collected during 24 h after intragastric administration. After processed ，bile sample 1 was preliminarily analyzed by HPLC. Another 5 SD rats were anesthetized and intubated in the same way as above ，and then given baicalin intragastrically （400 mg/kg）. The bile sample 2 was collected during 48 h after intragastric administration. After processed ，the bile sample 2 was isolated and purified by semi-preparative HPLC. The isolated metabolites were identified by using UV ，IR，MS and NMR ，as well as based on physical and chemical properties. MTT method combined with high content cell imaging analysis system was used to study the effect of the metabolites on the proliferation of HepG 2 cells. RESULTS ：Baicalin was mainly metabolized into metabolite 1 and metabolite 2 through bile. After isolation and purification ， they were identified as oroxylin A- 7-O-β-D-glucuronide and 2726719792@qq.com baicalein 6-O-β-D-glucuronide. The results of MTT assay showed that the metabolite 2 had a significant inhibitory effect 分析。E-mail：gaoxl@gmc.edu.cn on the proliferation of HepG 2 cells，and its IC 50 was 90 µg/mL；the results of high content cell imaging analysis showed that at a certain concentration metabolite 2 may inhibit proliferation by changing the mitochondrial distribution and membrane permeability of HepG 2 cells（studies on the pharmacological activities of metabolism 1 had been reported ，it was skipped in this study ）. CONCLUSIONS ：In this study ，two baicalin bile metabolites were successfully isolated and identified ，of which baicalein 6-O-β-D-glucuronide has a significant inhibitory effect on the proliferation of HepG 2 cells.

Objective: The Four Medical Tantras is a classic work of Tibetan medicine, in which drug treatment is one of the four main treatment methods, and prescriptions are the main form of clinical drug use. The study on the medication rules of The Four Medical Tantras has positive significance for the clinical medication research of Tibetan medicine. Method: Prescriptions recorded in Secret Medical Code and Follow-up Medical Code from The Four Medical Tantras were collected, the prescription database was constructed by Visual FoxPro 9.0, combined the dual perspectives of the " fifteen categories" (skabs bco lnga) of Tibetan medical diseases and the " eighteen practices" (lag len bco brgyad) of treatment, and Gephi 0.9.2 complex network was used to analyze its medication rules. Result: The Four Medical Tantras contained 2 695 Tibetan medicine prescriptions, average number of drugs in each prescription was 6.6, prescription composed of ≤ 7 drugs accounted for 69.2%of the total prescription. There were 1 002 kinds of medicines involved in the total prescription, of which 156 was the nodal degrees of Chebulae Fructus, Bambusae Concretio Silicea, Carthami Flos, Piperis Longi Fructus and Zingiberis Rhizoma and so on; followed by 91 nodal degrees of butter (mar), sugar, barley sweetener (sbang ma), honey and brown sugar and so on, which were Tibetan medicinal and edible medicines. According to the classification of diseases in the fifteen categories, there were 495 prescriptions for traumatology (mtshon rma), 323 for fever (tsha ba), 278 for toxics and 197 for three factors diseases. According to the treatment method of eighteen practices, 162 powder, 77 decoction, 84 laxative (bxhal) and others were used. Association rule analysis found that edge weights of Borneolum Syntheticum, Bambusae Concretio Silicea, Carthami Flos, Santali Albi Lignum and other cold medicines were 59, edge weights of pomegranate seeds, Piperis Longi Fructus, Cinnamomi Cortex, Amomi Fructus Rotundus and other warm medicines were 45. Conclusion: The Four Medical Tantras has some characteristics, including the medication rules of elliptic philosophy with cool-warm medicinal properties as the dual core, elimination-diarrhea (zhi-sbyong) as medication methods, weight of rlung-mkhris pa-bad kan as medication dialectical thinking and so on. Among them, the clinical application of butter, barley sweetener, sugar and other special delivery agents of Tibetan medicine is prominent. The prominent clinical application of special Tibetan medicines embodies the philosophy of Tibetan culture with the emphasis on overall balance. It has the multi-dimensional medication rule of " diet plus medicine, medicine plus therapy", and has positive significance for revealing the research on medication rules of Tibetan medicine.

Objective To investigate whether the effects of rapamycin on promoting oral squamous cancer cell apoptosis is related with inhibiting TLR4 expression and inflammatory factor IL-6 and PGE2 expression.Methods Human oral squamous carcinoma SCC-15 cell line was cultured and interfered by rapamycin.Then the activity of SCC-15 cells was detected by CCK 8,the SCC-15 cells apoptosis was detected by the Hochest33342/PI double staining,the invasion ability was determined by the transwell method.The TLR4 protein expression level was detected by Western blot and IL-6 and PGE2 expressions were detected by ELISA.Results Rapamycin could promote cell apoptosis,the invasion ability of SCC-15 cells was significantly decreased.After rapamycin intervention,the TLR4 protein expression was decreased and expression levels of IL-6 and PGE2 were reduced,showing statistical difference as compared with the negative group (P＜0.05).Conclusion Rapamycin promotes oral squamous cancer SCC-15 cell apoptosis,which may be related with inhibiting TLR4,IL-6 and PGE2 expression.

Patients with burning mouth syndrom(BMS,n =12)and patients with wisdom tooth removal(controls,n =9)were included. Immunohistochemistry and image analysis were used to quantify P2X3 receptor expression in lingual nerve fibres.A pain history and score were recorded on a visual analogue scale(VAS)prior to obtaining a lingual biopsy.The value of P2X3 receptor positive fibres in BMS and control subjects was 0.56 ±0.29 and 0.15 ±0.06 respectively(P <0.001).There was no significant correlation between P2X3 and VAS scores(R2 =0.012).Increased P2X3 may play a role in BMS but not correlated with the VAS score.