Objective: To investigate the status and influencing factors of disease uncertainty among caregivers of colorectal cancer patients receiving chemotherapy, so as to provide insights into psychological interventions among caregivers. Methods: Caregivers of colorectal cancer patients hospitalized in Hunan Cancer Hospital, the Third Xiangya Hospital and the Second Xiangya Hospital for chemotherapy from March 2020 to December 2021 were recruited. Caregivers' demographics, health status, medical and nursing support and social support, as well as patients' demographics, frequency of chemotherapy and disease stage were collected using questionnaire surveys. Caregivers' disease uncertainty was evaluated using Chinese version of the Uncertainty in Illness Scale for Family Members, and factors affecting caregivers' disease uncertainty were identified using a multivariable linear regression model. Results: A total of 318 caregivers were enrolled, including 115 men (36.16%) and 203 women (63.84%), with a mean age of (45.89±6.57) years, and there were 186 caregivers as patients' spouses (58.49%). The mean score of disease uncertainty was (86.65±10.82) points, and the scores of the unpredictability dimension, uncertainty dimension, complexity, and lack of information dimension were (3.21±0.35), (2.98±0.48), (2.84±0.49) and (2.36±0.59) points, respectively. There were 285 participants with a high level of disease uncertainty (89.62%), and multivariable linear regression analysis identified social support (β′=-0.199), medical and nursing support (β′=-0.118), patient's age (β′=-0.155) and stage Ⅲ and Ⅳ of colorectal cancer (β′=0.151) as factors affecting caregiver's disease uncertainty. Conclusion Caregivers of colorectal cancer patients with chemotherapy have a high level of disease uncertainty, which is affected by social support, medical and nursing support, patient's age and duration of disease.

Objective To study cutaneous ultrastructural changes and FERMT1 gene mutations in a patient with Kindler syndrome. Methods Clinical data were collected, and tissue samples obtained from the lesions of poikiloderma were observed by using transmission electron microscopy. Fifteen coding exons and their flanking sequences of the FERMT1 gene were amplified by PCR and DNA sequencing was followed.Results Reduplication of lamina densa was seen between the dermal-epidermal junctions of the lesional skin. The patient was found to be homozygous for a novel splice-site mutation (IVS9 + 1G ＞ A) in FERMT1 gene, and his parents were heterozygous for it. The mutation was undetected in fifty normal control individuals.Conclusions Transmission electron microscopy may serve as an ancillary examination for the diagnosis of Kindler syndrome. The IVS9+1G＞A mutation of FERMT1 gene may contribute to the clinical phenotype of Kindler syndrome in this patient.

Objective To study the change of the renal endogenous hydrogen sulfide (H2 S) pathway in the development of salt-sensitive hypertension in Dah1 rats.Methods Sixteen male Dah1 rats,in accordance with the random number table,were randomly divided into control group and high salt group fed with diet containing 80 g/kg NaCl.After 8 weeks,24 h urine sodium,24 h urinary protein,serum creatinine and serum urea were measured.The microstructural and ultrastructural changes in kidney were observed with light microscope and electronic microscope.The serum and kidney H2S contents were determined by using sulphur-sensitive electrode method.The mRNA levels of cystathionine β-synthase(CBS),cystathionine γ-lyase(CSE) and mercaptopyruvate sulfurtransferase(MPST) in renal tissue were determined by means of real-time polymerase chain reaction(RT-PCR).The protein expressions of CBS,CSE and MPST in renal tissue were detected by using Western blot.Results Compared with control group,high salt group rats had a significant rise in blood pressure,declined renal function,damaged renal structure,segmental glomerular sclero sis,small artery wall thickening,and occlusion of the lumen.Moreover,the endogenous H2S pathway in kidney of Dah1rats with high salt diet was downregulated markedly,demonstrated by the decreased serum and kidney H2S content,the reduced renal CBS,CSE and MPST mRNA expressions and CBS protein expression of kidney tissue.Conclusion The endogenous H2S/CBS pathway is downregulated during the development of salt-sensitive hypertension in Dah1 rats.

This study was aimed to compare the pharmacokinetics (PK) of Shengmai injection and Shenmai injection with a single injection administration using a constant speed in subjects with stable angina pectoris.A total of 20 subjects with stable angina pectoris were divided into two groups.Each group was administered with Shengmai and Shenmai injection.The liquid chromatography-mass spectrometry (LC/MS) was adopted to determine concentrations of ginsenosides in plasma at different time points.PK parameters were calculated for comparison.The results showed that after a single intravenous infusion of Shengmai and Shenmai injection,the Cm.of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in Shenmai group were higher than those of the Shengmai group with statistical significance (P ≤0.05).There were differences on the T1/2 of ginsenoside Rg1,AUC0-144h and CL of ginsenoside Rc,as well as Tmax of ginsenoside Rd (P ≤ 0.05).However,there was no significant difference shown on other PK parameters.It was concluded that after a single Shengmai or Shenmai injection,there were PK differences of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in the human body.The clinical medication selection should be based on syndrome differentiation and treatment of patients.

This study was aimed to establish the pharmacokinetics-pharmacodynamics (PK-PD) model of ginsenoside Rb1 following the intravenous administration of Shengmai injection in subjects with stable angina pectoris.A total of stable angina pectoris were selected and received Shengmai injection for 14 days.Plasma samples were collected at different time points.Plasma concentrations of ginsenoside Rb1 were determined by liquid chromatography-mass spectrometry (LC/MS).The concentration-time curves (AUC) were drawn,and then the PK parameters were calculated.The systolic pressure and diastolic pressure were monitored,and the combined PK-PD model was established based on the theory of effect compartment.The results showed that PK of ginsenoside Rb1 conformed to a mono-compartment model.The effect of Shengmai injection lagged behind the concentrations of ginsenoside Rb1 in plasma.The effect exhibited good correlation with ginsenoside Rb1 in effect compartment.The relationship between effect and plasma concentrations fits the Inhibitory Effect Imax model.It was concluded that the study successfully established the combined PK-PD model of ginsenoside Rb1 in subjects with angina pectoris.The model can efficiently evaluate the effective substance of Shengmai injection.

OBJECTIVE:To study the pharmacokinetics of the active ingredients of Shenmai injection,including ginsenoside Rg1 and ginsenoside Re,in normal Beagle dogs and those with myocardial ischemia. METHODS:6 Beagle dogs were given isopro-terenol hydrochloride (1.1 mg/kg) sc to establish the model of myocardial ischemia (model group). Another 6 Beagle dogs were given isometric normal saline (2.2 ml/kg) sc as controls group. The two groups of dogs respectively received corresponding drugs sc at 8:00 am and 13:00 pm on day 1 and at 8:00 am on day 2. Each group of dogs were given Shenmai injection(1.6 ml/kg)iv 1 h after administration on day 2,and such intravenous drip lasted for about 1 h. Blood was collected from each group 0,0.25, 0.5,0.75,1(the end of iv),1.5,2,3,4,6,8,12 and 24 h from the start of iv. Liquid chromatography-mass spectrometry was adopted to determine the concentrations of ginsenoside Rg1 and ginsenoside Re in blood,and WinNonlin 6.3 was used to calculate pharmacokinetic parameters for comparison. RESULTS:For ginsenoside Re in the dogs of the model group,t1/2 was(2.69±1.12) h,AUC0-24 h was(2 060.78±812.18)h·μg/L,Vz was(46.16±20.98)ml and CL was(9.02±4.45)ml/h;compared to the normal control group,AUC0-24 h was much greater and Vz and CL were significantly lower,showing a statistically significant difference(P<0.05). No significant difference in the pharmacokinetic parameters of ginsenoside Rg1 was shown between 2 groups(P>0.05). CON-CLUSIONS:Myocardial ischemia may affect the removal of ginsenoside Re in Beagle dogs,but has no effect on the pharmacoki-netic process of ginsenoside Rg1.

Objective:To investigate the gene expression of TCR V? subfamily T cells and clonality in peripheral blood CD4+ and CD8+ cells from patients with chronic myelogenous leukemia-chronic phase(CML-CP).Methods:The complementarity determining region 3(CDR3)of TCR V? subfamily genes in peripheral blood mononuclear cells(PBMCs),sorted CD4+ and CD8+ cells from 19 CML-CP patients were amplified using RT-PCR,the products were further by genescan analysis to identify the clonality of T cells.Results:Only 1 to 21 V? subfamilies were detected in peripheral blood CD4+ and CD8+ cells from patients with CML.The most frequent expression of V? subfamily was V?13 followed by V?9.Clonal expanded T cells in some V? subfamilies could be identified in both CD4+ and CD8+ cells,especially in CD8+ cells.The clonal expanded of V?21 subfamily in CD4+ cells and V?11 subfamily in CD8+ cells were identified most frequently.Conclusion:The restricted distribution of TCR V? repertoire has been found in CD4+ and CD8+ cells in patients with CML.Clonal expanded CD4+ cells and CD8+ cells have been identified which may relate to host immune response to CML antigen and may play a important role in anti-CML effect.

OBJECTIVETo investigate the roll of bone sialoprotein (BSP), a secreted glycoprotein, found in mineralized tissues in the development and progression of human esophageal squamous cell carcimoma (ESCC), and explore its association with clinicopathological characteristics and five-year survival of the patients.

METHODSThe expression of BSP was determined in 211 primary ESCC tumors and their paired nontumorous tissues using tissue-array, RT-PCR and immunohistochemistry.

RESULTSPrimary ESCC tissues showed a significantly higher expression rate of BSP mRNA than their paired nontumorous tissues (93.8% vs. 16.6%, P < 0.001), the same with BSP protein (56.9% vs. 31.3%, P < 0.001). The expression rate of BSP protein was correlated to lymph node metastasis and TNM stage (P < 0.05). The 5-year survival rate of BSP protein-positive ESCC patients was significantly lower than that of BSP protein-negative ESCC patients (P < 0.05). Multivariate analysis showed that tumor differentiation, TNM staging and BSP protein expression were independent factors affecting the prognosis of ESCC patients (P < 0.05).

CONCLUSIONSThe abnormal expression of BSP may play a significant role in the malignant progression and prognosis of ESCC, and BSP might be a marker reflecting the biologial behavior of ESCC.

Blotting, Western ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; Esophageal Neoplasms ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Integrin-Binding Sialoprotein ; genetics ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; Survival Rate

Objective:To comparatively evaluate the scan time and the accuracy of maxillary full-arch scans using four intraoral scanners (IOS) on conditions of the intraoral head-simulator and the hand-held model, and to evaluate the influence of different scanning conditions on digital scan.Methods:A upper dental arch model with melamine-formaldehyde resin teeth and silica gel gingiva that could be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language dataset as reference. Intraoral scans were performed on the model fixed on the head simulator by three researchers with four IOS [A: TRIOS 3; B: CS 3600; C: CEREC Omnicam; D: iTero]. For each scanner and each researcher, six scans were performed, to obtain the datasets as the head simulator group. And another six scans with each of the four intraoral scanners were performed by each researcher on the hand-held model to obtain the STL datasets as the hand-held group. The scan time were recorded for each scan. In the Geomagic Wrap software, the digital models were trimmed with only the teeth information retained and supreimposed by best fit alignment function and compared to obtain the root mean square (RMS) values of the discrepancies by three-dimensional compare function. The test datasets of each group were compared with the reference dataset for trueness. The six test scanning datasets with the same scanner of the same researcher were cross compared for precision. Mann Whitney U test was used to statistically analyze the difference values of the scan time, trueness and precision of the same intraoral scanner between head simulator group and hand-held group. Results:Compared to the hand-held group, the scan time of A [142(82) s] and D [119(52) s], which two IOS both with handle, were longer in head simulator group [A: 98(28) s; D: 85(22) s] ( P<0.01). However there were no significant differences between the two groups for scan time of IOS B and C ( P>0.05). For full-arch scan accuracy (trueness and precision), there were no significant differences between the two groups of IOS A and B ( P>0.05), while the trueness of C ( P<0.05) and the precision of D ( P<0.01) were better in head simulator group [C: 112(38) μm; D: 43(13) μm] compared to hand-held group [C: 135(47) μm; D: 53(18) μm]. However, there were no significant differences for the precision of C ( P>0.05) and the trueness of D ( P>0.05). Conclusions:The scan time and the accuracy of full-arch digital scans with different IOS may be effected by the scan conditions. For in vitro study of intraoral scanning, head-simulator can simulate the intraoral environment of the real patient to some extent. Meanwhile, the position of the dentist and the patient, and also the limited intraoral space during intraoral scanning are also simulated.

Objective:To comparatively evaluate the accuracy and the scan time of three full-arch scan strategies on the head-simulator, to explore a full-arch scan strategy with better clinical operability and high accuracy.Methods:A cross-controlled study design was used. A model with melamine-formaldehyde resin teeth and silica gel gingiva of an upper dental arch which can be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language (STL) dataset as reference. Intraoral scans were performed on the model fixed on the head simulator with four intraoral scanners (IOS) [A (TRIOS 3), B (CS 3600), C (CEREC Omnicam), D (iTero)]. The STL datasets were obtained from each of the four different IOS systems by using three scan strategies (scan strategies 1, 2 and 3 were composed of 10, 5 and 7 paths respectively) all by one attending doctor with 3 years of intraoral scanning experience. For each scanner and each scan strategy, nine scans were acquired. And the scan time was recorded for each scan. Following the scan strategy, the scan path was completed to obtain a full-arch digital model, and the scan time was recorded as full-arch scan time. Complementary scans were performed to fill the missing image, and this scan time was recorded as complementary scan time. The total scan time was obtained by adding full-arch scan time and complementary scan time. Through the Geomagic Wrap software, the three-dimensional (3D) models were overlaid by best fit alignment function and compared to obtain the root mean square values of the discrepancies by 3D compare function. The intraoral scanning datasets were compared with the reference for trueness. The nine intraoral scanning datasets were cross compared with same scan strategy and same intraoral scanner for precision.Results:There were no significant differences among the three scan strategies for trueness ( P>0.05), while the differences among the three scan strategies for precision were affected by difference IOSs ( P<0.05), and only scan strategy 3 showed the highest precision with all the four IOS. The full-arch scan time of scan strategies 1, 2 and 3 were (130±24), (72±17) and (90±19) s respectively ( P<0.05). For complementary scan time, scan strategy 2 [(50±24) s] took longer time than scan strategy 1 [(26±18) s] and scan strategy [(25±21) s] ( P<0.05), while no significant differences between the latter two ( P>0.05). For total scan time, scan strategy 1 [(156±31) s] took longer time than scan strategy 2 [(122±30) s ] and scan strategy 3 [(115±29) s ] ( P<0.05), while no significant differences between the latter two ( P>0.05). Conclusions:Full-arch scanning on the head-simulator with scan strategy 3 which can obtain scanning datasets with high accuracy, was more convenient to operate and took shorter scan time, and is generally suitable for intraoral scanners commonly used in clinic.