Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Background and purpose:Urothelial carcinoma(UC)is a prevalent malignant tumor of the urinary system,and early diagnosis is crucial for improving patient prognosis.This study evaluated the diagnostic efficacy of fluorescence in situ hybridization(FISH),urine cytology and their combination for UC,as well as for its different subtypes.Methods:This study included patients who underwent transurethral resection of bladder tumor(TURBT)from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center,No.:050432-4-2307E)that met the inclusion and exclusion criteria.We collected TURBT pathological results and pre-procedure FISH and cytology results.Diagnostic accuracy,sensitivity and specificity of FISH,cytology and their combination were analyzed and compared for urothelial carcinoma.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist and Standards for Reporting of Diagnostic Accuracy(STARD)were followed for this study.Results:A total of 283 patients were enrolled in this study,136 were diagnosed with UC,and 147 were not.Of the 136 UC cases,79(58.09%)were invasive and 57(41.91%)were non-invasive.In terms of malignancy grade,112(82.35%)were high-grade UC and 24(17.65%)were low-grade UC.Using histopathology as the gold standard,the accuracy of FISH,cytology and their combination in diagnosing UC was 79.51%,72.08%and 77.39%,respectively;sensitivity was 72.06%,58.82%and 78.68%,respectively;specificity was 86.39%,84.35%and 76.19%,respectively.The area under the curve(AUC)for FISH and the combination was similar but higher than that for cytology(0.792 vs 0.716,P=0.006;0.774 vs 0.716,P=0.004);the Net Reclassification Improvement(NRI)for FISH compared to cytology was 15.28%(P=0.006).In the 79 cases of invasive UC,FISH had higher accuracy than cytology(86.28%vs 78.32%,P=0.011).The sensitivity of FISH and the combination was higher than that of cytology(86.08%vs 67.09%,P=0.004;91.14%vs 67.09%,P＜0.001),and the AUC values were also higher(0.808 vs 0.713,P=0.004;0.784 vs 0.713,P=0.007).The NRI for FISH compared to cytology was 21.03%(P=0.003).In the 57 cases of non-invasive UC,the AUC values for all three methods were low(AUC＜0.700).Among the 112 cases of high-grade UC,FISH had higher accuracy(84.94%vs 76.45%,P=0.005),and the combination had higher sensitivity(89.29%vs 66.07%,P＜0.001)compared to cytology.The AUC values for FISH and the combination were also superior to that for cytology(0.847 vs 0.752,P=0.002;0.827 vs 0.752,P=0.001).The NRI for FISH compared to cytology was 19.01%(P=0.003).In the 24 cases of low-grade UC,the AUC values for all three methods were low(AUC＜0.600).Conclusion:For UC,particularly invasive and high-grade subtypes,FISH shows superior diagnostic efficacy compared to cytology.FISH alone offers accuracy and sensitivity comparable to the combination test,with higher specificity.In cases of non-invasive or low-grade UC,however,all three diagnostic methods demonstrate relatively low efficacy.

Background and purpose:Urothelial carcinoma(UC)is a prevalent malignant tumor of the urinary system,and early diagnosis is crucial for improving patient prognosis.This study evaluated the diagnostic efficacy of fluorescence in situ hybridization(FISH),urine cytology and their combination for UC,as well as for its different subtypes.Methods:This study included patients who underwent transurethral resection of bladder tumor(TURBT)from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center,No.:050432-4-2307E)that met the inclusion and exclusion criteria.We collected TURBT pathological results and pre-procedure FISH and cytology results.Diagnostic accuracy,sensitivity and specificity of FISH,cytology and their combination were analyzed and compared for urothelial carcinoma.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist and Standards for Reporting of Diagnostic Accuracy(STARD)were followed for this study.Results:A total of 283 patients were enrolled in this study,136 were diagnosed with UC,and 147 were not.Of the 136 UC cases,79(58.09%)were invasive and 57(41.91%)were non-invasive.In terms of malignancy grade,112(82.35%)were high-grade UC and 24(17.65%)were low-grade UC.Using histopathology as the gold standard,the accuracy of FISH,cytology and their combination in diagnosing UC was 79.51%,72.08%and 77.39%,respectively;sensitivity was 72.06%,58.82%and 78.68%,respectively;specificity was 86.39%,84.35%and 76.19%,respectively.The area under the curve(AUC)for FISH and the combination was similar but higher than that for cytology(0.792 vs 0.716,P=0.006;0.774 vs 0.716,P=0.004);the Net Reclassification Improvement(NRI)for FISH compared to cytology was 15.28%(P=0.006).In the 79 cases of invasive UC,FISH had higher accuracy than cytology(86.28%vs 78.32%,P=0.011).The sensitivity of FISH and the combination was higher than that of cytology(86.08%vs 67.09%,P=0.004;91.14%vs 67.09%,P＜0.001),and the AUC values were also higher(0.808 vs 0.713,P=0.004;0.784 vs 0.713,P=0.007).The NRI for FISH compared to cytology was 21.03%(P=0.003).In the 57 cases of non-invasive UC,the AUC values for all three methods were low(AUC＜0.700).Among the 112 cases of high-grade UC,FISH had higher accuracy(84.94%vs 76.45%,P=0.005),and the combination had higher sensitivity(89.29%vs 66.07%,P＜0.001)compared to cytology.The AUC values for FISH and the combination were also superior to that for cytology(0.847 vs 0.752,P=0.002;0.827 vs 0.752,P=0.001).The NRI for FISH compared to cytology was 19.01%(P=0.003).In the 24 cases of low-grade UC,the AUC values for all three methods were low(AUC＜0.600).Conclusion:For UC,particularly invasive and high-grade subtypes,FISH shows superior diagnostic efficacy compared to cytology.FISH alone offers accuracy and sensitivity comparable to the combination test,with higher specificity.In cases of non-invasive or low-grade UC,however,all three diagnostic methods demonstrate relatively low efficacy.

Objective:To investigate the application and effect of the virtual reality (VR) combined with the augmented reality (AR) integrated teaching system in stomatology general medical education of clinical medicine students.Methods:A total of 160 undergraduates from the five-year clinical medicine Batch 2015 of Naval Medical University were randomly divided into VR+AR group and traditional group, with 80 students in each group. A comparative analysis was made on the previous and teaching achievements of the two groups of students, and a questionnaire survey was conducted after the completion of the class. Epidata 3.0 was used to input questionnaire data, and SPSS 23.0 software was used to carry out t test, chi-square test and Fisher precision test. Results:There was no statistical difference in written test scores between the VR+AR group and the traditional group [(52.65±3.76) vs. (51.90±3.46), P=0.516], but the VR+AR group was significantly higher than the traditional group in case analysis scores [(35.85±2.56) vs. (31.40±2.96), P < 0.001] and overall performance [(88.50±4.95) vs. (83.30±4.86), P= 0.002]. The questionnaire survey results showed that the scores of "teaching mode" [(92.30±6.90) vs. (85.20±7.30), P<0.001], "teaching method" [(91.70±5.90) vs. (86.00±6.70), P=0.012] and "teaching improvement" [(90.70± 8.70) vs. (82.30±8.40), P<0.001] in VR + AR group were significantly higher than those in the traditional teaching group. Conclusion:The VR combined with AR integrated teaching system can significantly improve teaching performance and teaching quality, and is convenient for teaching demonstrations and simulation operations in small oral spaces, and is especially suitable for oral general medical education for clinical medicine.

Objective:To conduct theoretical analysis and experimental research on peripherally inserted venous catheters, establish theoretical models of interaction between different materials catheters and simulated skin tissues, and test different catheters at the same time to provide theoretical basis and experimental basis for the optimization design.Methods:According to the mechanical properties of the catheter at 25 ℃ and 37 ℃, a finite element model of the catheter and simulate skin tissue was established. The relationship between catheter folds and material and structure during puncture was analyzed, and the stiffness, radiographic properties, etc. were tested experimentally.Results:The performance of the catheter at different temperatures is closely related to its material. The wrinkle situation of the catheter is related to the catheter material and the inclination of the wedge surface. The elastic modulus of the polyurethane (PU) catheter is about 500 MPa and 250 MPa, respectively at room temperature (25 ℃) and body temperature (37 ℃), which meets the clinical needs of high rigidity during puncture and soft material during indwelling. When the catheter structure is the same, the PU catheter is less prone to wrinkles than the fluorinated ethylene propylene copolymer (FEP) catheter. When the catheter material is the same, the smaller the inclination of the wedge surface, the less likely the catheter to wrinkle.Conclusions:Appropriately reducing the inclination of the wedge-shaped surface of the needle of peripherally inserted venous catheters can improve the success rate of puncture. The PU catheters have good mechanical properties, they are not prone to wrinkles during puncture, and their stiffness can be reduced at body temperature, which can not only increase the success rate of puncture, but also reduce the occurrence of complications. Therefore, PU catheters have a better clinical application prospect.

Radiotherapy plays an important role in the treatment of cervical cancer. The radiosensitivity of cervical cancer is closely related to genes, RNA regulation, tumor microenvironment, drugs and other factors. Recently, many studies have been conducted to continuously explore the mechanisms of these factors in radiotherapy sensitization, and progress has been made in radiotherapy sensitization of cervical cancer at basic or clinical level.

Objective To compare and analyze the relationship between geometric parameters of the needle of different insulin pens and their puncture force, flow rate, and pressing force. Methods The human skin tissue model and needle model were established, and the finite element simulation analysis of needle puncture was performed. Using a test platform, 25 kinds of needles with different geometric parameters were tested for the puncture force, pushing pressure, flow rate and other parameters. The influence of geometric parameters on the performance of the needles were analyzed. Results The puncture force of the needle was closely related to its section design. Compared with the three-section needle, the five-section needle increases the secondary inclination angle and the condyle angle, increases the contact area between the needle and the tissue, and make the change of the contact angle more smoothly, which reduce the needle penetration force. The smaller the outer diameter of the needle, the smaller the penetrating power. The larger the inner diameter of the needle, the greater the fluid flow rate, the smaller the pushing pressure, and the higher the injection accuracy. Conclusions Five-section, ultra-thin-walled or ultra-thin-walled needles have more excellent performance. On the basis of ensuring the strength of the needle, the needle's geometry can be optimized to reduce the puncture force. The results of this study can provide theoretical basis and experimental basis for the design of needles for insulin pens.

Time series model was developed to investigate the effect and contributions of related biomarkers on the cerebral endothelial dysfunction induced by beta amyloid(Aβ). HCMEC/D3 was incubated with 2. 5 μmol/L Aβ for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 h, and biomarkers including cytosolic calcium ion, mitochondrial membrane potential(MMP), endothelial nitric oxide synthase(eNOS)and cell viability were determined. Time series model was established to assess the dynamic relationship between the related biomarkers and cell viability and the contribution of different biomarkers to cell damage. Impulse response analysis indicated that after a positive impact on cytosolic calcium ion, cell viability decreased and this impact continued to decline; after a positive impact on endothelial nitric oxide synthase and mitochondrial membrane potential, cell viability increases, which increased rapidly in the early stage, and the rate decreased in later stage. The result of variance decomposition showed that the cytosolic calcium ion played a major role in cerebral endothelial dysfunction induced by Aβ. Combined with the model study, it is concluded that the intervention on the level of cytosolic calcium ion at the early stage may be the possible way to slow the disease progression.

Objective To observe the efficacy and safety of Bushen Huoxue Prescription in the treatment of kidney deficiency and blood stasis type primary osteoporosis. Methods Totally 50 patients with kidney deficiency and blood stasis type primary osteoporosis were collected. They were given Bushen Huoxue Prescription granules twice a day, taking with water, for 12 weeks. Before and after treatment, the femoral neck, Ward's area, L1–4 bone mineral density (BMD) were measured. VAS and TCM syndrome integrals were evaluated before and 4, 8 and 12 week of treatment. The level of serum osteocalcin (OC), β-C-terminal telopeptides of type I collagen (β-CTX) and osteoprotegerin (OPG) were detected before and after treatment. Hematuria routine, liver and kidney function were under safety testing before and after treatment. Results Bushen Huoxue Prescription could significantly increase BMD of left femoral neck and Ward's triangle (P=0.001, P=0.044). L1–4 BMD increased, without statistical significance (P=0.172). The total effective rate was 60.870% (28/46) for L1–4 and left femoral neck and 58.696% (27/46) for Ward's triangle. The VAS and TCM syndrome integral decreased significantly 4 weeks treatment compared with that before the treatment (P<0.01), and the scores decreased significantly with the prolongation of treatment time (F=159.690, P<0.001; F=163.970, P<0.001). After 12 weeks, treatment, the total effective rate for TCM syndromes was 78.26% (36/46). Serum levels of OC and β-CTX showed a tendency to increase, while serum levels of OPG showed a tendency to decrease, without statistical significance (P=0.087, P=0.091, P=0.419). There was no serious adverse reaction in hematuria routine and liver and kidney function. Conclusion Bushen Huoxue Prescription has obvious clinical efficacy for kidney deficiency and blood stasis type primary osteoporosis, which can improve the patients' BMD, improve bone metabolism, relive bone pain, with high level of safety.