Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

Background Other infectious diarrhea (OID) refers to infectious diarrhea other than cholera, dysentery, and typhoid/paratyphoid fever. In the global climate change context, frequent extreme temperature events pose a significant threat to population health, yet the association between extreme temperatures and OID remains unclear. Objective To understand the impact of extreme temperature events on the incidence of OID in Taizhou region, and provide a scientific basis for formulating targeted public health intervention strategies. Methods Case data of OID from 2016 to 2024 and meteorological and pollutant data of Taizhou, Zhejiang during the same period were collected. The case data were derived from National Notifiable Infectious Diseases Reporting System, while the meteorological data and pollutant data were obtained from National Meteorological Science Data Center and Taizhou Ecology and Environment Bureau, respectively. An extreme heat event is defined as a period of two or more consecutive days in the warm season during which the daily mean temperature exceeds the 90th percentile value for that season. Similarly, an extreme cold event is defined as a period of two or more consecutive days in the cold season during which the daily mean temperature falls below the 10th percentile value. A distributed lag nonlinear model based on Poisson regression was used to assess the impact of extreme temperatures on OID incidence. Furthermore, subgroup analyses were conducted by gender and age. Results From 2016 to 2024, a total of 108 670 OID cases were reported in Taizhou, with higher incidence in males (61 253 cases) than females (47 417 cases). In terms of single-day lag effect, exposure to extreme cold presented an inverted U-shaped risk pattern: a significant risk effect began to emerge on the 4th day after exposure, continued to rise, and reached a peak on the 7th day (RR=1.044, 95%CI: 1.029, 1.058), whereas extreme heat had no significant impact. In terms of cumulative lag effect, exposure to extreme cold presented a J-shaped cumulative effect curve: short-term exposure (0-2 days) showed no risk effect, but as time extended (0-9 days), a risk effect emerged and reached the maximum risk value during the 0-12 d cumulative period (RR=1.243, 95%CI: 1.057, 1.461). In contrast, extreme heat had no cumulative lag effect. The subgroup analysis revealed that under extreme cold exposure, the single-day lag effects for both males and females exhibited an inverted U-shaped curve, with the risk peaking on day 7 for males (RR=1.045, 95%CI: 1.026, 1.065) and day 8 for females (RR=1.041, 95%CI: 1.019, 1.064). The risk pattern in the 1-5 years age group was similar to that of the overall population but with a higher effect size (RR=1.063, 95%CI: 1.041, 1.085). In terms of the cumulative lag effects, the cumulative risk curves for both males and females under extreme cold exposure showed a J-shaped pattern with varied risk profiles. Significant variations in risk patterns were observed across different age groups. No significant cumulative lag effects were observed for extreme heat exposure in any subgroup. Conclusion Extreme cold can increase the incidence of OID in Taizhou, and the risk effects are heterogeneous among different groups. No risk effect is observed for extreme heat.

ObjectiveTo determine the prevalence of hepatitis C virus （HCV） infection and identify the underlying risk factors among drug users in Taizhou City of Zhejiang Province during 2009‒2020. MethodsA consecutive cross-sectional survey was conducted. A total of 400 drug users in correctional settings were randomly selected from April to August. The drug users were interviewed with a questionnaire to collect demographic characteristics， AIDS-related knowledge， detoxification service， drug use， and sexual behavior. Blood samples were then collected for anti-HCV antibody testing. Chi-square test and multivariate conditional logistic regression were used. ResultsA total of 5 042 drug users were included in this study. Seroprevalence of HCV was determined to be 22.7%. From 2009 to 2019， the seroprevalence showed a significant downward trend， from 34.9% to 8.8% （χ²=221.025， P<0.001）. However， in 2020， the seroprevalence was 12.7%. The multivariate logistic regression analysis showed that senior age （≥25 years old）， cohabitation， taking traditional or mixed drugs， injection drug use， and needle sharing were risk factors associated with HCV seroprevalence. ConclusionSince 2009， HCV seroprevalence among drug users in Taizhou City has shown a downward trend， however， it has increased slightly in 2020. It warrants strengthening prevention and treatment measures in response to risk factors related to HCV infection among drug users.

Objective To optimize the parameters for the diffusion tensor imaging (DTI)of the ulnar nerve in elbow.Methods 5 groups of DTI sequences with different b values and numbers of diffusion gradient directions (NDGDs)were used to collect ulnar nerve images from 13 volunteers,and then the diffusion tensor tractography (DTT)was established.The fractional anisotropy (FA),apparent diffusion coefficient (ADC),length of ulnar nerve fiber and DTI image quality were compared under different imaging parameters. Results DTI results for 18 normal ulnar nerves were included in the study.Under different imaging conditions,FAs showed no significant differences.With constant NDGDs,increasing b value decreased both image quality and ADCs of the ulnar nerve.NDGDs had no significant effects on ADCs or image quality.When b=1 000 s/mm2 and NDGDs=20,the length of the ulnar nerve fiber was the longest and DTT had the best subjective scoring in image quality.Conclusion b=1 000 s/mm2 and NDGDs=20 is recommended for DTI of elbow ulnar nerve,so as to obtain high image quality and stable observing targets.

Objective To observe the effects and safety of oxycodone hydrochloride combined with parecoxib sodium in preventing postoperative hyperalgesia induced by remifentanil. Methods Eighty-eight ASA Ⅰ or Ⅱ patients undergoing elective laparoscopic myomectomy surgery were randomly divided into four groups (C,O,P,PO) with 22 cases in each group. Patients in group C,O,P,PO were given with 10 mL saline, 0.1 mg?kg-1 oxycodone hydrochloride, 40 mg parecoxib sodium, 0.1 mg?kg-1 oxycodone hydrochloride and 40 mg parecoxib sodium 30 min before the end of the surgery, respectively. The VAS scores were recorded at the end of surgery 30 min, 1 h, 2 h, 4 h, 8 h, and the cases of agitation, rigor, vomiting and increasing of analgesics were recorded. Results Compared with group C, the VAS scores in group O, P,PO were significantly lower(P<0.05). The VAS scores in group PO were lower than those in group O,P(P<0.05). The cases of agitation and rigor in group PO (0.0%, 5.0%) were less than those in group C (45.0%,23.0%) (P<0.05). The increased doses of analgesics in group PO(0) were less than those in groups C (12), group P (5), and group O (5)(P<0.05). Conclusion Oxycodone hydrochloride combined with parecoxib sodium can effectively prevent postoperative hyperalgesia induced by remifentanil, and reduce the incidence of postoperative agitation.

The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors(TKIs)erlotinib and gefitinib are standard second-line therapies for non-small cell lung cancer. For patients without the EGFR mutation,more and more evidence has suggested the superiority of chemotherapy over targeted therapy. Adding targeted agents to standard second-line treatment is an trend of exploration,but without promising results nowadays. Crizotinib,targeting at anaplastic lymphoma kinase,has been shown excellent efficacy for second-line therapy in non-small cell lung cancer.

Objective To evaluate the effects of dexmedetomidine on the activity of nuclear factor kappa B (NF-κB) in neutrophil granulocytes during one-lung ventilation in the patients undergoing pulmonary lobectomy.Methods Thirty-eight ASA physical status Ⅰ or Ⅱ patients,aged 40-64 yr,weighing 50-75 kg,scheduled for elective pulmonary lobectomy,were randomized into 2 groups (n =19 each) using a random number table:control group (group C) and dexmedetomidine group (group D).In group D,dexmedetomidine 1.0 μg/kg was infused intravenously over 15 min before induction of anesthesia,followed by infusion at a rate of 0.5 μg· kg-1 · h-1 until 30 min before the end of operation.The equal volume of normal saline was given in group C.At 5 min after intubation,0,30 and 60 min of one-lung ventilation,0 and 30 min of two-lung ventilation,and 30 min after operation,blood samples were taken from the radial artery for blood gas analysis and for measurement of plasma concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).The oxygenation index and respiratory index were calculated.The nuclear protein of neutrophil granulocytes was extracted for measurement of NF-κB DNA-binding activity.Results Compared with group C,the respiratory index,plasma concentrations of TNF-α and IL-6 and NF-κB DNA-binding activity were significantly decreased,and no significant difference was found in the oxygenation index in group D.Conclusion Dexmedetomidine can inhibit the activation of NF-κB in neutrophil granulocytes and is helpful in reducing the systemic inflammatory responses during one-lung ventilation in the patients undergoing pulmonary lobectomy.

Objective To determine the median effective plasma concentration of remifentanil (EC50) inhibiting cardiovascular response to tracheal intubation and skin incision when combined with propofol in patients of Uighur nationality.Methods Thirty ASA Ⅰ or Ⅱ Uighurs aged 20-60 yr with body mass index of 18-30 kg/m2 undergoing elective laparoscopic cholecystectomy were enrolled in this study.Anesthesia was induced and maintained with propofol infusion.BIS value was maintained at 40-50.TCI of remifentanil was then started.The initial target plasma concentration (Cp) was 6.0 ng/ml.EC50 of remifentanil was determined by modified Dixon' s upand-down sequential experiment.Each time Cp increased/decreased by 0.5 ng/ml.Tracheal intubation was facili.tated with cisatracurium 0.2 mg/kg at 2 min after a new Cp was set when target effect-site concentration (Ce) was balanced with Cp.Positive cardiovascular response was defined as increase in SBP by 15％ and/or HR ＞ 90 bpm lasting＞15 s.The EC50 (95％ confidence interval) of remifentanil blunting responses to tracheal intubation and skin incision was calculated.Results EC50 (95 ％ confidence interval) of remifentanil inhibiting cardiovascular response to tracheal intubation and skin incision when combined with propofol was 3.4 (2.3-4.5) ng/ml and 3.8 (2.8-4.9) ng/ml respectively.Conclusion When depth of anesthesia was maintained at BIS value 40-50 with propofol infusion,the EC50 of remifentanil inhibiting cardiovascular response to tracheal intubation and skin incision is 3.4 and 3.8 ng/ml respectively.