Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m²) vs. (60±15) mL/(min·1.73 m²), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

【Objective】 To explore the influencing factors of adolescent runaway and its correlation with family health so as to provide epidemiological evidence for future comprehensive interventions. 【Methods】 Using the quota sampling method, 1 065 adolescents aged 12-18 years old were surveyed by Questionnaire Star in 120 cities in China from July to September 2021. A well-developed electronic questionnaire was used to collect information about demographic characteristics, psychological characteristics, family health, social support, and behavior of running away from home. Univariate analysis and Logistic regression were used to explore the influencing factors of adolescent runaway and its correlation with family health. 【Results】 A total of 1 065 adolescents were investigated, among whom 334 were the only children (31.36%) and 442 were boys (41.50%). Univariate analysis revealed that 7.6% of teenagers had the experience of running away from home in the last 30 days. Participants who were ethnic minorities (P=0.031) and had education of technical school or junior college (P=0.029) and a low family income (P<0.001) were more likely to have running away behavior. Adolescents with low self-efficacy (P=0.005), depression (P<0.001), anxiety (P<0.001), and more stress had higher detection rates of runaway behavior. However, adolescents with higher family health and social support were less likely to run away from home (P<0.01). Multivariate analysis showed that compared with adolescents with low family health, adolescents with high (OR=0.16, 95% CI: 0.06-0.46) and moderate (OR=0.27, 95% CI: 0.14-0.55) family health had a significantly lower risk of runaway behavior. 【Conclusion】 The family is of great significance in preventing teenagers from running away from home. Parents should build a good parent-child relationship and create a happy family atmosphere to reduce the occurrence of teenagers running away from home.

Objective:We employ different regimens of induction therapy in living donor ABO-incompatible kidney transplantation(ABOi-KT) recipients to compare their clinical outcomes during 6 months post-KT.Methods:A retrospective analysis was conducted for the relevant clinical data of 41 ABOi-KT recipients from June 2018 to September 2022.Thirteen recipients on induction therapy of anti-human T lymphocyte porcine immunoglobin(pATG)were enrolled in pATG group; 19 recipients on induction therapy of basiliximab in basiliximab group; 9 recipients on induction therapy of rabbit anti-human thymocyte immunoglobulin(rATG)in rATG group.Differences in age, gender, body mass index(BMI), dialysis modality/duration, sideness of donor kidney, frequency of blood group antibody treatment, dose of rituximab, basic blood group antibody titers of IgG/IgM, and the gender and BMI of recipient's donor were compared for three groups.Immune status was assessed by comparing absolute lymphocyte count before pre-treatment and within 6 months post-KT in recipients under different induction regimens among 3 groups by one-way analysis of variance.Transplant kidney function was assessed by comparing the levels of serum creatinine, estimated glomerular filtration rate(eGFR)and serum urea nitrogen using one-way analysis of variance.The incidence of delayed graft function(DGF), acute rejection(AR)and infection was compared among three groups.Results:Regarding baseline profiles, except for donor age pATG group[(60.23±6.10)years]versus basiliximab group[(51.95±6.97)years]was statistically significant( P=0.002), the differences in the remaining parameters were not statistically significant among three groups(all P>0.05). At Day 1/3/7/10/14 post-KT, absolute lymphocyte counts were(0.17±0.07)×10 9/L, (0.27±0.14)×10 9/L, (0.85±0.40)×10 9/L, (1.05±0.56)×10 9/L and(1.10±0.56)×10 9/L in pATG group and(0.69±0.04)×10 9/L, (0.18±0.21)×10 9/L, (0.57±0.44)×10 9/L, (0.67±0.45)×10 9/L and(0.81±0.46)×10 9/L in rATG group respectively.They were all higher than those in basiliximab group[(0.46±0.18)×10 9/L, (0.67±0.26)×10 9/L, (1.29±0.48)×10 9/L, (1.56±0.49)×10 9/L, (1.75±0.53)×10 9/L]and the differences were statistically significant(all P<0.05). No statistically significant difference existed in absolute lymphocyte count among 3 groups before pre-treatment and after Day 21 post-KT(all P>0.05). At Week 1/2/4/12/24 post-KT, the differences in serum levels of creatinine and urea nitrogen were not statistically significant( P>0.05). At Month 1/3 post-KT, eGFR was(47.24±14.51)and(49.94±14.31)ml·min -1·(1.73 2) -1 in rATG group and they were lower than(67.36±21.60)and(65.00±14.67)ml·min -1·(1.73 2) -1 in basiliximab group with a statistically significant difference( P<0.05). However, at Week 1/2/24 post-KT, no statistically significant difference existed in eGFR among 3 groups( P>0.05). In ATG, basiliximab and rATG groups, DGF(1 case, 1 case, 1 case), AR(2 cases, 2 cases, 1 case)and infection(4 cases, 7 cases, 3 cases)occurred during 6 months post-KT. Conclusions:Through a limited sample of single centers, no statistically significant difference existed in graft function recovery for ABOi-KT recipients on induction therapies of pATG, basiliximab and rATG.And DGF, AR and infections occurred in all three groups.However, there were little inter-group differences.

Objective:To prepare pH-sensitive liposomes to avoid the degradation of monophosphoryl lipid A (MPLA) by lysosomes.Methods:Using DOPE and CHEMS as carrier materials, pH-sensitive liposomes were prepared by thin-film dispersion method. Particle sizes and Zeta potential of the liposomes were detected by dynamic light scattering. The morphological features of pH-sensitive liposomes under different pH conditions were observed by transmission electron microscopy. Flow cytometry was performed to detect the phagocytosis of liposomes by THP-1 and DC2.4 cells. Confocal laser microscopy was used to observed the colocalization of liposomes and lysosomes. BALB/c mice were immunized with hepatitis B surface antigen (HBsAg) using MPLA pH-sensitive liposome as an adjuvant. The levels of serum anti-HBs were quantitatively detected by ELISA. IFN-γ and IL-2 spot forming cells (SFCs) in mouse splenic lymphocytes were detected by ELISPOT.Results:The pH-sensitive liposomes were constructed with an average particle size of (90.90±1.13) nm, polydispersity index (PDI) of 0.076±0.013 and Zeta potential of (-27.900±0.666) mV. As the pH value of the solution decreased, the particle size increased significantly and the liposomes presented irregular shapes, indicating the pH-sensitive features. The phagocytosis rates by THP-1 cells and DC2.4 cells were 10.40% and 12.40% for pH-sensitive fluorescent liposomes, and 1.09% and 0.28% for fluorescent liposomes. Confocal laser microscopy revealed that pH-sensitive fluorescent liposomes were phagocytosed by THP-1 cells and existed in the cytoplasm, while fluorescent liposomes existed in lysosomes. Compared with MPLA liposomes, MPLA pH-sensitive liposomes could significantly improve the cellular immune response in mice. The levels of IFN-γ and IL-2 SFCs in the MPLA pH-sensitive liposome group were significantly higher than those in the MPLA liposome group ( P<0.01) and the non-adjuvant group ( P<0.001). Conclusions:The pH-sensitive liposome delivery system could improve the utilization of MPLA as an adjuvant.

Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.

Objective:To investigate the recovery of patients with acute thallium poisoning after 9 years.Methods:A group of 14 patients with familial thallium poisoning who were admitted to our hospital in 2010 were followed up for 9 years.Results:Among the 14 patients with acute thallium poisoning, one patient died on the 14th day after poisoning, and all the other survivors were followed up 9 years later. The general condition of all the patients was significantly better than that of poisoning 9 years ago. The alopecia of all cases disappeared, the newborn hair grew normally, without gastrointestinal symptoms, numbness, pain in the limbs and mental symptoms. All the patients returned to normal intelligence and physical strength and had a normal life. One patient (No. 5) gave birth to 2 children successively after discharge. The first child was 6 years old and the second child was 2 years old. Both growth and intelligence were not different from those of the same age. Currently, the third pregnancy was more than 7 months. No.6 and No.10 patients were poisoned in their teenage and were currently all studying in university. No.6 patient suffered from Hashimoto's thyroiditis 7 years after poisoning, and he has been taking thiamazole tablets for two years. Poisoned infants, No.7, 8 ,11 and 12, were school-age children with normal growth, mental development and excellent academic performance. Among the 13 surviving patients, blood and urine samples from No. 1, No. 3, and No. 4 patients were collected, and no thallium concentration was detected, and biochemical examina-tion and neurological examination were all normal.Conclusions:Patients with acute thallium poisoning have a favorable prognosis according to the follow-up after 9 years. All patients have no obvious sequelae and have normal labor ability. Young women have normal fertility, and children have normal growth and mental development.

Objective:To investigate therole of serum amylase elevation in the evaluation of diabetic ketoacidosis (DKA) patients and the related factors affecting serum amylase (AMS) levels in patients with diabetic ketoacidosis.Methods:A total of 249 patients with DKA who were admitted to the First Affiliated Hospital of Zhengzhou University from November 2011 to August 2018 were selected for this retrospective study. The patients were divided into the normal group ( n=176) and the elevated group ( n=73) according to the AMS level measured by fasting venous blood samples. The enumeration data such as sex, type of DM, diabetic vascular complications, number of deaths, number of ICU monitoring, and number of acute pancreatitis (AP) after discharge were analyzed by chi-square test or Fisher test, and the measurement data such as age, pH, HbA1c, CO 2CP, Ca 2+, BUN, and Scr were analyzed by independent sample t test to compare the difference between the two groups. Results:The intensive care unit (ICU) monitoring rate was 50.7%, the median length of stay in ICU was 4 days, the median length of hospital stay was 14 days, and the median treatment cost was 28 000 yuan, which were higher in the elevated group than those in the normal group ( P<0.05). There were no significant differences in mortality, AP during hospitalization, and the probability of AP after discharge between the elevated group and the normal group ( P>0.05). The duration of diabetes, the number of previous DKA, the incidence of diabetic vascular complications, HbA1c, pH, BUN, and Scr in the elevated group were all higher than those in the normal group ( P<0.01 or P<0.05). Conclusions:DKA patients with elevated AMS are more likely to be admitted to ICU, and the length of stay in ICU, total length of hospital stay and total cost of treatment are all increased. Where as the overall mortality rate during hospitalization and the likelihood of AP after discharge are not increased.

Objective:To express the recombinant varicella-zoster virus (VZV) gE Δ-Fc fusion protein using CHO cell expression system, and provide reference for screening candidate antigens of recombinant herpes zoster vaccines. Methods:A eukaryotic expression plasmid containing the gE Δ-Fc gene was transfected into CHO cells. Monoclonal cells were selected by methionine sulfoximine (MSX) pressure screening and limited dilution method to obtain the CHO cells secreting and expressing the gE Δ-Fc fusion protein. The expressed gE Δ-Fc fusion protein was purified by MabSelect SuRe affinity chromatography. The binding activity of gE Δ-Fc fusion protein to Fc receptors was identified by ELISA. Flow cytometry was used to detect the phagocytosis of antigens by DC2.4 cells. Antibody titers in serum samples of BALB/c mice immunized with the gE Δ-Fc fusion protein were detect by ELISA. Results:A CHO cell line stably expressing the gE Δ-Fc fusion protein was obtained. Flow cytometry suggested that the phagocytotic activity of DC2.4 cells against the gE Δ-Fc fusion protein was stronger than that against gE. Moreover, the gE Δ-Fc fusion protein could induce BALB/c mice to produce high titers of specific anti-VZV antibodies. Conclusions:The recombinant VZV gE Δ-Fc fusion protein expressed in CHO cells had a good immunogenicity. This study provided reference for screening candidate antigens of recombinant herpes zoster vaccines.

Objective: This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. Methods: Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. Results: The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p<0.001) and negative PR expression (p=0.007) were independently associated with LVSI. Both Kaplan-Meier method and univariate Cox regressions showed LVSI negative and positive cases had similar tumor-specific survival (TSS) and disease-free survival (DFS). After adjusting for the influence of adjuvant therapy and other clinicopathological factors with multivariate Cox regressions, LVSI still could not bring additional survival risk to the patients (p=0.280 and p=0.650 for TSS and DFS, respectively). This result was verified by Kaplan-Meier survival analyses after propensity score matching (p=0.234 and p=0.765 for TSS and DFS, respectively). Conclusion LVSI does not significantly compromise the survival outcome of Chinese EEC patients.

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.
Adult ; Aged ; Aged, 80 and over ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Carcinoma, Renal Cell ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; genetics ; Female ; Follistatin-Related Proteins ; genetics ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; Male ; Middle Aged ; NF-kappa B ; genetics ; Neoplasm Metastasis ; Signal Transduction ; genetics ; Tumor Suppressor Proteins ; genetics