Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

OBJECTIVE To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects. METHODS UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway. CONCLUSION The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.

Objective:To perform acceptance test and performance assessment for Siemens Biograph Vision 600 positron-emission tomography/computed tomography(PET/CT)according to the national health industry standard WS 817-2023.Methods:Spatial resolution,sensitivity,scatter fraction,count loss and random coincidence,correction accuracy of count loss and random coincidence,time-of-flight(TOF)resolution of the PET component within the PET/CT system were tested through the measurement program(NU2-2018)of National Electrical Manufacturers Association(NEMA),which was installed inside of the equipment,in accordance with the requirement of national health industry standard WS 817-2023.The PET/CT registration accuracy was measured through Gantry_offset acquisition program that was built into the equipment.Results:The transversely and axially spatial resolutions of Biograph Vision 600 PET/CT were respectively 3.69 mm and 4.10 mm at 1 cm away from the center of visual field,and were respectively 4.26 mm and 4.89 mm at 10 cm away from the center of visual field,and were respectively 4.68 mm and 4.89 mm at 20 cm away from the center of visual field.The sensitivity of 10 cm away from center and radial of visual field were respectively 16.12 kcps/MBq and 16.00 kcps/MBq.The peak value of noise equivalent count rate(NECR)was 281.60 kcps,and the corresponding radioactivity concentration of peak value was 30.69 kBq/ml.The NECR peak value,scatter fraction and maximum value of the error of relative count rate were respectively 38.17% and 4.0%.The TOF resolution was 209.87 ps when the radioactivity concentration was 5.3 kBq/mL.The registration accuracy values of Biograph Vision 600 PET/CT were 0.347 mm,-0.226 mm and 3.659 mm at the directions of x,y and z axis.Conclusion:It is feasible to perform the acceptance test according to the WS 817-2023 standard through uses the NEMA NU2-2018 standard measurement program that is installed inside of the equipment.The performance indicators can meet requirement of standard as the current national standard GB/T 18988.1-2013 and the health industry standard WS 817-2023 that will being implemented in the test of Biograph Vision 600 PET/CT,which can pass acceptance.

BACKGROUND:Total knee arthroplasty is an effective treatment for late-stage osteoarthritis,but postoperative pain and joint function recovery are the main challenges.Nerve block and mixed drug injection are two common pain relief methods,but the effect of their combined use is still unclear. OBJECTIVE:To investigate the effects of ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia on postoperative pain relief and joint function recovery in total knee arthroplasty. METHODS:120 patients with osteoarthritis admitted to Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine from January to May 2022 were randomly divided into two groups(n=60).The observation group received ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia.The control group received ultrasound-guided continuous adductor canal block+single sciatic nerve block.The differences in visual analog scale score,hospital for special surgery score,pain mediators,expression levels of inflammatory factors,the occurrence of adverse reactions,and postoperative barehanded muscle strength test were compared between the two groups. RESULTS AND CONCLUSION:(1)The visual analog scale scores at rest and exercise were lower in the observation group than those in the control group at 6,8,12,24,48,and 72 hours postoperatively(P<0.05).(2)Hospital for special surgery scores at 1 and 3 months postoperatively were significantly higher in the observation group than those in the control group(P<0.05).(3)In terms of pain mediators and inflammatory factors,the expression levels were significantly lower in the observation group than those in the control group(P<0.05).(4)There was no statistically significant difference in terms of adverse effects and postoperative barehanded muscle strength examination between the two groups(P>0.05).(5)In total knee arthroplasty,ultrasound-guided continuous adductor canal block and single sciatic nerve block,together with a"cocktail"mixed drug analgesia injected into the joint cavity,can provide excellent analgesia,facilitate the recovery of joint function,and relieve postoperative pain and inflammation with a high degree of safety.

Objective:To study exposure doses and radiation levels of thyroids,eye lenses and hands of technologists who worked in the single-photon emission computed tomography/computed tomography(SPECT/CT)room,so as to provide a reference for assessing radiation hazards and radiation protection of technologists in SPECT/CT machine room.Methods:During February 2019 and October 2020,2 technologists each of two SPECT/CT machine rooms of the department of nuclear medicine of Cancer Hospital,Chinese Academy of Medical Sciences were selected,and the optically stimulated luminescence(OSL)dosimeters were used to monitor the exposure doses of four technologists in the SPECT/CT room in 7 quarters.The total amount that they put positions of patients were 20 682 patients.The technologist routinely wore lead aprons(0.5 mmPb)and lead collars(0.5 mmPb)during clinical work.OSL dosimeters were placed on the thyroids,the locations nearby the eyes and hands of each technologist.Each one of 4 technologists wore a set of dosimeters(included three sets for the thyroid,the locations nearby the eye and hand).The monitoring period that technologists wore OSL dosimeters was 21 months.The personal dose equivalent[Hp(10)]of thyroid at 10 mm depth,the personal dose equivalent[Hp(3)]of the location nearby eyes at 3 mm depth,and the personal dose equivalent[Hp(0.07)]of hands at 0.07 mm were monitored as quarter.The exposure doses of the thyroids,eye lens and hands of 4 technologists in SPECT/CT machine room were assessed on the basis of these results of measurements.All four technologists also underwent dose monitor of routine external radiation.Results:The average number of each technologist who put position was approximately 2 955 patients.Among of the four technologists,the exposure doses of thyroid,eye lens and hand of only one technologist were highest,which were respectively 0.129,0.071 and 0.151 mSv,while they were far below the constraint values(5,5 and 125mSv/a)of dose for radiation workers.Conclusion:The four technologists of the SPECT/CT room directly contact with patients who have been injected with radiopharmaceuticals during they put the positions of patients.But,the exposure doses of their thyroid,eye lenses and hands are far below the constraint value of dose for radiation workers.The reasonable use of personal protective equipment as requirement can effectively safeguard against radiation exposure during technologist put position of patient.