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.

Objective:To analyze the electrophysiological characteristics and influencing factors of peripheral neuropathy in Parkinson's disease(PD)patients.Methods:Totally 68 PD patients and 30 controls were selected for neuroelectrophysiological evaluation, including items such as limb motor nerve terminal latency(LP)and amplitude and sensory nerve conduction velocity(SCV)and amplitude.Age, sex, serum folate, vitamin B 12, homocysteine and hemoglobin levels were also recorded for the two groups.The Hoehn-Yahr scale was used to assess patients and levodopa daily doses and levodopa equivalent daily doses were calculated.According to the criteria for neuroelectrophysiological abnormalities, 31 PD patients were found to have peripheral neuropathy and 37 PD patients did not have peripheral neuropathy. Results:In PD patients, a total of 952 peripheral nerves were examined, with 21.7% having motor nerve involvement(118/544)and 72.8%(297/of 408)having sensory nerve involvement.In the control group, a total of 420 peripheral nerves were examined, with 4.2%(10/240)having motor nerve involvement and 26.1%(47/180)having sensory nerve involvement.Compared with the control group, the wave amplitudes of motor nerve terminals were reduced in the PD group for the ulnar nerve( t=2.172/2.345, right/left), median nerve( t=2.104/2.543, right/left), and tibial nerve( t=2.340/2.444, right/left)(all P<0.05); compared with the control group, the wave amplitudes of sensory nerve terminals of the ulnar nerve( Z=3.535/3.439, right/ left), median nerve( Z=3.076/2.937, right/left), and peroneal nerve( Z=2.795/2.795, right/left)were all reduced in the PD group(all P<0.05); compared with the control group, sensory conduction velocities of the ulnar nerve( t=2.326/2.487, right/left), median nerve( t=3.269/2.386, right/left), and peroneal nerve( t=2.551/2.418, right/left)were prolonged(all P<0.05). The rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=149.814, P<0.001)was higher than that of abnormalities with motor nerve terminal wave amplitude in PD patients; the rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=58.364, P<0.001)was higher than that of abnormalities with sensory conduction velocities.Logistic regression analysis showed that increased folic acid( OR=0.825, 95% CI: 0.637-0.990)and vitamin B 12( OR=0.996, 95% CI: 0.991-1.000)were protective factors for PD peripheral neuropathy; H-Y score, levodopa daily dose( OR=1.009, 95% CI: 1.003-1.015), and increased homocysteine( OR=1.151, 95% CI: 1.041-1.273)were risk factors for PD peripheral neuropathy.After excluding confounding factors, H-Y classification( OR=3.213, 95% CI: 1.342-7.713)remained an independent risk factor for peripheral nerve injury in PD patients. Conclusions:In PD patients with peripheral neuropathy, both motor nerves and sensory nerves are involved, sensory nerves are more significantly involved, and axonal damage is more important than myelin loss; increased H-Y classification is an independent risk factor for peripheral nerve injury in PD patients.

Objective:To investigate the neuroprotective effect of histone deacetylase 3 (HDAC3) specific inhibitor RGFP966 on traumatic brain injury (TBI) and its mechanism in rats.Methods:Forty-eight SD rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+RGFP966 group ( n=12). Rats in the later 3 groups accepted hydraulic impact brain injury to establish TBI models; and then, RGFP966 (dissolved in 1% DMSO at a dose of 10 mg/kg) was injected intraperitoneally 30 min after modeling, twice a day for 3 d, in TBI+RGFP966 group; same amount of DMSO was injected into TBI+vehicle group at the same time. Three d after modeling, neurological function was tested by modified neurological severity score (mNSS), water content of brain tissues was detected by dry-wet weight method, proportion of injured neurons at the frontal cortical tissues on the affected side was detected by Nissl staining, expressions of HDAC3 and pyroptosis related proteins were detected by immunohistochemical staining and Western blotting, and serum content of inflammatory factors was detected by ELISA. Results:Three d after modeling, compared with the TBI+vehicle group, the TBI+RGFP966 group had significantly decreased mNSS scores (9.83±0.75 vs. 6.67±0.82), water content of the injured cerebral cortex (82.73%±0.36% vs. 80.92%±0.66%), proportion of damaged neurons (75.60%±7.44% vs. 55.87%±4.10%), and HDAC3 protein expression (0.67±0.09 vs. 0.51±0.07), and significantly increased acetylated H3 (Ace-H3) and acetylated H4 (Ace-H4) protein expressions (0.81±0.02 vs. 1.22±0.02; 0.74±0.01 vs. 1.07±0.02), and statistically decreased protein expressions of nuclear factor-κB (NF-κB, 1.20±0.05 vs. 0.94±0.04), NOD-like receptor thermal protein domain associated protein 3 (NLRP3, 0.72±0.02 vs. 0.40±0.03), Caspase-1 containing cysteine (Caspase-1), dermatin D N-terminal fragment (GSDMD-N, 0.71±0.03 vs. 0.52±0.01), significantly decreased NF-κB and NLRP3 immunohistochemical staining scores, and significantly decreased serum contents of tumor necrosis factor-α, interleukin(IL)-1β and IL-18 ( P<0.05). Conclusion:Early intervention with RGFP966 after TBI can reduce the pyroptosis and inflammatory reaction of nerve cells and play neuroprotective role, whose mechanism may be related to inhibited activation of NF-κB/NLRP3/GSDMD pathway.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.

Objective To explore the effect of a multimodal electroencephalogram ( EEG) data visualiza-tion system on the motor imagery ability of stroke survivors. Methods Twenty stroke patients were randomly di-vided into an experimental group and a control group, each of 10. Both groups were provided with brain-computer interface-based motor imagery ( MI) training. At the same time, the experimental group was monitored and guided using an online, multimodal EEG data visualization system developed in our department. The classification accuracy ( CA) and event-related desynchronization ( ERD) of the 2 groups′ motor imagery were compared before and after the treatment. Results Before the treatment, no significant differences in the average CA of MI were found be-tween the experiment group (50.92±2.08) and the control group (49.35±4.20)(P>0.05). After the treatment, however, the experimental group′s average CA had increased to (64.52±5.27), significantly higher than that of the control group (51.18±5.02). When the stroke patients imaged affected upper extremity movements, obvious ERD was observed in the α frequency around the bilateral central motor regions of both groups, especially in the experi-mental group, but without significant differences between the two groups. However, no significant changes were found in the ERD of theβwaves of the two groups( P>0.05) . Conclusion The proposed online multimodal elec-troencephalogram data visualization system can help stroke patients imagine movements actively. It is worth sprea-ding in clinical practice.

Items of design and signature from clinical trial drugs were made , the occurrence ratio of every item in 2265 informed consent form ( ICF) from 63 clinical trial drugs in Beijing Youan Hospital affiliated to Capital U-niversity of Medical Sciences were analyzed , and items with lower occurrence ratio were explored .Generally , the design and signature of ICF met the requirement of GCP .However , there were some defects of ICF and antonym of signature .Based on the analysis on the problems , some measures were put forward:formulate relevant standard op-erating procedures , strengthening the management of informed consent , and strengthen the system construction and education training , promote the hospital ethics construction , to protect the rights and interests of the subjects .

Objective To observe the response of left ventricular (LV)function and structure to chronic intermittent hypoxia (CIH)early stage in New Zealand white rabbits by echocardiography.Methods The New Zealand white rabbits were placed in the CIH chamber and exposed to hypoxia for 8 weeks (6 hours/day,6 days/week).The flow of nitrogen and oxygen were regulated into the customized chambers by the gas control delivery system.The fraction of inspired oxygen was changed from 21 % to 8% for 25 s of every 1 70 s.LV structure and function was assessed by echocardiography at CIH 0,1 ,2,4,6,8 weeks and histopathology was done by HE staining simultaneously.Results ①LV structural variables:compared with 0 week,LV posterior wall and interventricular septum thickness thickened at 6 week.LV end diastolic increased at 8 week (P < 0.05 ).② LV systolic function variables:compared with 0 week,LV ejection fraction increased at 2 week and 4 week,decreased at 6 week and 8 week,but it was higher than 0 week (P < 0.05).Isovolumic contraction time (IVCT)decreased at 1 week,2 week,4 week (P <0.05 ).③LV diastolic function variables:compared with 0 week,Peak velocity of early diastolic period increased at 2 week and 4 week,decreased at 6 week and 8 week with E/A>1 .Isovolumic relaxation time (IVRT)decreased at 1 week and 2 week,but increased at 8 week (P < 0.05 ).④ The myocardial pathology showed that myocardial fibers disordered slightly,cardiomyocytes swelled,nuclei increased and intracellular edema when exposed to CIH for 2 week and 4 week.Vacuolar degeneration,edema and congestion were found in intercellular substance at 6 week and 8 week.Conclusions ① LV systolic and diastolic function compensation started at CIH early stage then LV structure abnormality advent later.②IVCT and IVRT are sensitive indicators of LV systolic and diastolic function compensation.

objective To assess the DNA damage of radiation workers in different grade hospitals,and to explore the correlation between the types of work or work time and the levels of DNA damage.Methods DNA single strand break were detected by using alkaline single cell gel electrophoresis(SCGE),and the comet was analyzed with CASP(Comet Assay Software Project).TDNA,TL,TM and OTM were calculated.Results The parameters of SCGE in the radiation greup were higher than those of control group(F=3.93,P<0.01).The significant difference was found not only among the different types of work or difierent work time,but also among the different grade hospitals(F=1.83,1.9 1,P<0.05).Conclusions Various levels of DNA damage could be detected in the radiation workers of the two hospitals.DNA damage of radiation workers is less serious in the higher-grade hospital than the lower grade one.Different types of work or work time might affect the DNA damage level.