Relationship between lung injury caused by cardiopulmonary bypass and acetyltransferase p300 in rats / 中华麻醉学杂志

Objective:To evaluate the relationship between lung injury induced by cardiopulmonary bypass (CPB) and acetyltransferase p300 (p300) in rats.Methods:Eighteen SPF healthy adult male Sprague-Dawley rats, aged 12-16 weeks, weighing 350-450 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (S group), CPB group, and CPB+ left lung ischemia-reperfusion (I/R) group (CPB+ IR group). CPB group was connected to CPB pipeline for cardiopulmonary bypass. The lung I/R injury model was prepared by clamping the left lung hilum for 45 min followed by opening during CPB, 30 min later CPB was terminated, and mechanical ventilation was continuously performed for 1.5 h before ending the experiment in CPB+ IR group. Arterial blood gas analysis was performed and oxygenation index (OI) and respiratory index (RI) were calculated before CPB, at 10 min after opening the lung hilum, and immediately after the end of experiment. The bronchoalveolar lavage fluid (BALF) and left lung tissues were collected immediately after the end of experiment for determination of the concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in BALF and total protein in BALF and concentrations of IL-17 in lung tissues (by enzyme-linked immunosorbent assay), expression of p300, phosphorylated p300 (p-p300), and acetylated histone H3 (AC-H3) in lung tissues (by Western blot) and expression of p-p300 (using immunohistochemical staining) and for microscopic examination of the pathological changes of lung tissues (under the light microscope) which were scored. Results:Compared with S group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB and CPB+ IR groups ( P<0.05). Compared with CPB group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB+ IR group ( P<0.05). Conclusions:The mechanism by which CPB induces lung injury may be related to up-regulation of the expression of p300 and enhancement of activity of p300 in lung tissues and increased release of inflammatory factors in rats.

Small case study of retinopathy associated with novel coronavirus infection / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical and multimodal imaging features of retinopathy associated with novel coronavirus disease 2019(COVID-19)infection, investigate the related risk factors, and analyze the treatment and prognosis.METHODS: A total of 7 patients(7 eyes)with clinically confirmed COVID-19-associated retinopathy in Tianjin Medical University General Hospital from December 13, 2022 to January 13, 2023 were included in the study. All patients underwent color fundus photography, IR, spectral-domain optical coherence tomography(SD-OCT), fundus autofluorescein(FAF)and other ophthalmic examination and serological examination.RESULTS: Among the included patients, 2 cases(2 eyes)of central retinal vein occlusion(CRVO)appeared differently from previous CRVO. The hemorrhagic features of CRVO were round or fusiform shape hemorrhagic spots with white centers. One of them, the von Willebrand factor antigen(vWF: Ag)level was increased to 161.8%. The other case was positive in serologic test for lupus anticoagulant. In 2 cases(2 eyes)of multiple evanescent white dot syndrome(MEWDS), FAF showed that dots of high spontaneous fluorescence were scattered in the posterior pole. The prognosis of 2 MEWDS were good after the treatment of glucocorticoids. The 3 cases(3 eyes)of acute macular neuroretinopathy(AMN)showed reddened brown lesions in the macular area, hyporeflective lesions with clear boundaries on IR, and high signal intensity in the ONL and ELM, EZ/IZ signal fracture on SD-OCT.CONCLUSION: COVID-19 may cause inflammatory storm, involving all layers of retinal tissues and blood vessels, leading to the occurrence of various retinal lesions. Hormone therapy may be effective and the prognosis is good in most cases. Roth spot can be seen in fundus hemorrhage of CRVO, lupus anticoagulant and increased vWF: Ag may be risk factors for CRVO after COVID-19.

Intervention effect of HSP60 on learning and memory impairment induced by combined exposure to lead and hypertension in mice / 中国职业医学

ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients / 中国药房

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database / 中华心血管病杂志

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Clinical and multimodal imaging features of acute macular neuroretinopahy associated with COVID-19 / 中华眼底病杂志

Objective:To observe the clinical and multimodal imaging characteristics of eyes with acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective clinical study. From December 18 to 26, 2022, 16 eyes of 8 patients with AMN associated with COVID-19 were included in the study. There were 4 males and 4 females; all cases were bilateral. The age was (31.5±9.6) years old. The time from fever to decreased vision was (3.75±1.04) days. The best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundus microscopy, fundus color photography, and optical coherence tomography (OCT) were performed in all patients. Infrared fundus photography (IR), OCT angiography (OCTA) and fluorescein fundus angiography (FFA) were performed in 14, 6 and 4 eyes respectively. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for statistics. The clinical data, IR, OCT and OCTA imaging features of the patients were retrospectively analyzed.Results:The logMAR BCVA of AMN eyes was 4.21±0.74, intraocular pressure was (14.87±1.50) mm Hg (1 mm Hg=0.133 kPa). Fundus color photography showed that multiple gray-white petal-shaped lesions were arranged around the macular fovea in 2 eyes; no obvious abnormality was found in the macular area in 14 eyes. Of the 14 eyes examined by IR, 6 eyes had irregular weak reflective lesions around the macular fovea. OCT showed strong reflex in the outer nuclear layer and outer plexiform layer of all eyes, including 15 eyes with elliptical zone injury. In 6 eyes examined by OCTA, the blood flow density of the superficial and deep capillary plexus (DCP) of retina decreased, and the blood flow density of DCP decreased significantly. The en-face image of DCP showed the wedge-shaped strong reflective lesion area with the tip pointing to the central fovea in 2 eyes. No abnormal fluorescence was observed in FFA.Conclusions:The characteristic manifestation of AMN associated with COVID-19 is weak reflex focus in IR; OCT shows strong reflection in outer core layer and outer plexiform layer; OCTA showed that retinal DCP blood flow density decreased.

Superficial retinal blood flow density analysis and related factors in adolescents with different classification of high myopia / 中华眼底病杂志

Objective:To observe and analyze the superficial retinal blood flow density and its related influencing factors in the macular area of adolescents with different types of non-pathological high myopia (HM).Methods:A retrospective clinical study. From March to August 2022, 117 eyes of 117 adolescents who were admitted to Liaocheng Aier Eye Hospital due to myopia were included in the study. According to equivalent spherical degree (SE) and corneal curvature, subjects were divided into mild myopia or emmetropia group (control group), HM group, occult HM (OHM) group, and super HM (SHM) group, with 30 eyes, 28 eyes, 35 eyes, and 24 eyes, respectively. All subjects underwent medical optometry, intraocular pressure, optical coherence tomography (OCT), OCT angiography (OCTA), axial length (AL) and corneal curvature measurements. The diopter was SE. OCTA instrument was used to scan the macular region in the range of 6 mm×6 mm, and the software automatically divided it into three concentric circles centered on the fovea of the macular, namely, the central area with a diameter of 1 mm, the inner ring area with a diameter of 1-3 mm, and the outer ring area with a diameter of 3-6 mm. The superficial retinal vascular density (SRVD), vascular perfusion density (SBPD), the area, perimeter (PERIM), avascular index (AI) of foveal avascular area (FAZ) and retinal thickness were measured in the macular region as a whole and in different regions. One-way analysis of variance was used to compare the data among groups, and the least significant difference t-test was used to compare the data among groups. The correlation of AL, corneal curvature and intraocular pressure with SRVD and SBPD in macula was analyzed by Pearson correlation analysis. Results:There were significant differences in SRVD and SBPD in the central, inner and outer regions of macula in control group, HM group, OHM group and SHM group ( P<0.05). There were statistically significant differences in the thickness of the retina above, below and on the temporal side of the central and outer ring regions ( P<0.05). However, no statistically significant difference was in the thickness of the retina on the nasal side ( P>0.05). There was no significant difference in PERIM ( P>0.05). There were significant differences in FAZ area and AI ( P<0.05). Correlation analysis showed that AL was negatively correlated with SRVD and SBPD in macular whole and central, inner and outer ring regions ( P <0.05). Corneal curvature and SE were positively correlated with the SRVD and SBPD of macular whole, central area and outer ring area ( P<0.05). AL was negatively correlated with retinal thickness in the outer ring region ( P<0.05). SE was positively correlated with the thickness of the retina above, below and temporally in the outer ring region ( P<0.05). AL was negatively correlated with FAZ area and AI ( P<0.05). SE was positively correlated with FAZ area and PERIM ( P<0.05). Retinal thickness was positively correlated with SRVD and SBPD ( P<0.05). Conclusions:The SRVD and SBPD of different types of HM in adolescents decreases to different degrees. The thickness of the retina in the central region is thicker, and the retina in the outer ring region is thinner. With the decrease of SRVD, the retinal thickness gradually is thinner.

Effect of different immune induction therapies on early clinical outcomes of ABO-incompatible kidney transplantation recipients of living relative donor / 中华器官移植杂志

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.

The Deubiquitinating Enzyme USP14 Promotes the Proliferation and Migration Ability of Pancreatic Cancer Cells / 中国生物化学与分子生物学报

Pancreatic cancer remains one of the deadliest cancer types with few effective treatment options. While the overexpression of ubiquitin-specific protease 14 (USP14) has been observed in many tumor cells, including pancreatic cancer cells, its precise role in pancreatic cancer is not well defined. Here, we investigated the biological function of USP14 in pancreatic cancer and its molecular mechanisms. Our analysis of the Cancer Genome Atlas database revealed that USP14 was highly expressed in pancreatic cancer tissues,and further investigation revealed that its expression level was negatively correlated with the prognosis of patients. In SW1990 and MIAPaCa2 pancreatic cancer cells,we established stable USP14-knockdown cell lines using the shRNA-USP14 lentivirus and found that USP14 knockdown inhibited the proliferation and migration ability of pancreatic cancer cells by CCK8, colony formation assay, wound-healing and Transwell assays. Western blotting analysis showed that downregulation of USP14 expression resulted in a decrease in CyclinD3 protein levels, while overexpression of USP14 increased the protein levels in SW1990 and MIAPaCa2 pancreatic cancer cells. Furthermore, co-immunoprecipitation demonstrated that USP14 interacts with CyclinD3 and ubiquitination assays show that overexpression of USP14 reduces the ubiquitination level of CyclinD3. Moreover, CRISPR / Cas9-mediated USP14 knockout in SW1990 pancreatic cancer cells resulted in decreased CyclinD3 protein levels. These findings suggest that USP14 promotes the proliferation and migration ability of pancreatic cancer cells by interacting with CyclinD3, highlighting USP14 as a potential therapeutic target for pancreatic cancer.

Early application of tacrolimus extended-release capsule after kidney transplantation / 器官移植

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.

Meta-analysis of condylar changes produced by a Twin-block appliance in Class Ⅱ malocclusion / 华西口腔医学杂志

OBJECTIVES@#To evaluate the effects of a Twin-block appliance on the condyles of patients with ClassⅡmalocclusion by conducting a systematic review and a Meta-analysis.@*METHODS@#Pubmed, Embase, Cochrane Library, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and VIP Database were electronically searched. Randomized controlled trials, controlled clinical trials, and single-arm trials on condylar changes produced by a Twin-block appliance in patients with ClassⅡmalocclusion were included. Two reviewers independently extracted and assessed the risk of bias. Meta-analyses were conducted with Review Manager 5.3.@*RESULTS@#Eight studies were included; among which, seven were of high quality. After treatment with a twin block appliance, condyles moved anteriorly. The anterior joint spaces decreased (P<0.000 01), whereas the posterior spaces increased (P<0.000 01). The superior spaces were not changed (P=0.11). Moreover, a significant difference was observed in the increase of the condylar space index (P<0.000 01). After treatment, the anteroposterior diameters of the condyles and condylar height increased (P=0.000 2 and P<0.000 01, respectively). By contrast, no significant changes were discovered in the medial external diameters of the condyles (P=0.42).@*CONCLUSIONS@#A Twin-block appliance can promote the growth of a condyle in the posterior and upper direction and move it forward in favor of the correction of Class Ⅱ malocclusion.

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis / 国际口腔科学杂志·英文版

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

Effects and mechanisms of SNP-9 on Parkinson''s disease cell model induced by rotenone / 中国药科大学学报

@#In this article, the effects and mechanisms of SNP-9 on Parkinson''s disease (PD) cell model were investigated.SH-SY5Y cells were treated with rotenone to establish PD cell model; the effects of rotenone and SNP-9 on cell viability were detected by MTT assay; Hoechst/PI double staining assay was used to detect the effects of rotenone and SNP-9 on cell apoptosis; DCFH-DA probe was used to detect the effects of rotenone and SNP-9 on cellular reactive oxygen species (ROS) levels; and Western blot was used to detect the effects of rotenone and SNP-9 on protein levels of tyrosine hydroxylase (TH), α-synuclein (α-syn), Bcl-2 and Bax.The results showed that SNP-9 could alleviate abnormalities in cell viability, levels of TH and α-syn, apoptosis, ROS and apoptotic relative protein Bax/Bcl-2 induced by rotenone.Our findings suggest that SNP-9 may alleviate rotenone-induced injury in neuronal cells by regulating cell apoptosis related pathway.

Effects and mechanisms of SNP-9 on Aβ25-35-induced damage in bEnd.3 cells / 中国药科大学学报

@#In order to investigate the effects of neuroprotective peptide SNP-9 which is derived from silk fibroin hydrolysate on the injury of the blood-brain barrier in Alzheimer′s disease (AD), Aβ25-35 was used to damage brain microvascular endothelial cells bEnd.3 to establish AD injury model and drug intervention was performed.MTT assay was used to detect the effects of SNP-9 and Aβ25-35 on cell viability.RT-qPCR was used to determine the effects of SNP-9 and Aβ25-35 on the mRNA levels of tight junctions (TJs)-related ZO-1, occludin and claudin-5.Western blot was used to detect the effects of SNP-9 and Aβ25-35 on the protein levels of TNF-α, phosphorylated NF-κB, NF-κB, IκBα and RAGE.The results showed that SNP-9 reduced bEnd.3 cell damage induced by Aβ25-35, and improved the abnormal mRNA levels of ZO-1, occludin and claudin-5 in model cells.It alleviated the abnormal protein levels of TNF-α, phosphorylated NF-κB, IκBα and RAGE induced by Aβ25-35. These results suggest that SNP-9 may regulate the levels of TNF-α in model cells by influencing RAGE/NF-κB pathway, and then ameliorate TJs-related abnormalities and alleviate bEnd.3 cell injury induced by Aβ25-35.

Application of short-term training path for prenatal ultrasound diagnostician in primary hospitals / 中华医学教育探索杂志

Objective:To explore the establishment and effect of short-term training path for prenatal ultrasound diagnosticians in primary hospitals.Methods:A total of 105 trainees from in total 5 batches of the "prenatal ultrasound screening training base" in Chongqing were selected as the research objects, and a combination of multiple teaching methods was used to carry out specialized training for primary prenatal ultrasound screening doctors before and after training. Theoretical examinations and practical operation assessments were performed, and after training, remote image quality control and continuous improvement methods were established for trainees to assess training effectiveness. SPSS 21.0 was used for t test, Wilcoxon test and chi-square test. Results:After training, the results of the theoretical examinations and practical operation examinations of the trainees were higher than those before the training ( P<0.05), and after the completion of the training, the number of trainees who returned to their original units to carry out prenatal ultrasound examination, the average number of prenatal ultrasound examinations per month and the number of referrals to higher prenatal diagnosis centers of each trainee increased significantly ( P<0.05). Conclusion:The establishment of short-term training path for prenatal ultrasound diagnosis can effectively improve the professional theoretical knowledge and practical operation level of prenatal ultrasound doctors in primary hospitals, and greatly solve the problem of technical promotion under the shortage of grassroots hospitals.

Efficacy of repetitive transcranial magnetic stimulation combined with health education in the treatment of refractory depression and its effects on cognitive function and sleep quality / 中国基层医药

Objective:To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with health education in the treatment of refractory depression and its effects on cognitive function and sleep quality.Methods:Ninety patients with refractory depression who received treatment in Hangzhou Seventh People's Hospital from January 2018 to January 2021 were included in this study. They were randomly assigned to receive either rTMS (control group, n = 45) or rTMS combined with health education (observation group, n = 45). All patients received 4 weeks of treatment. Clinical efficacy, the scores of the Clinical Global Impressions (CGI) Scale and the Hamilton Rating Scale for Depression (HAMD), cognitive function, sleep quality, and quality of life pre- and post-intervention were compared between the two groups. Results:Total response rate was significantly higher in the observation group than in the control group [91.11% (41/45) vs. 71.11% (32/45), χ2 = 5.87, P < 0.05]. CGI scores post-intervention were significantly higher in the observation group than in the control group [(45.23 ± 7.89) points vs. (27.64 ± 4.53) points, t = 12.97, P < 0.05]. HAMD scores were significantly lower in the observation group than in the control group [(16.32 ± 2.76) points vs. (21.86 ± 3.98) points, t = 7.67, P < 0.05]. The number of categories achieved and the number of correct responses post-intervention in the observation group were (3.83 ± 0.61) and (85.45 ± 7.87), respectively, which were significantly higher than those in the control group [(2.98 ± 0.37), (73.25 ± 6.12), t = 7.99, 8.20, both P < 0.05]. The number of perseverative errors post-intervention in the observation group was significantly lower than that in the control group [(32.02 ± 1.89) vs. (35.12 ± 2.09), t = 7.38, P < 0.05]. The Pittsburgh Sleep Quality Index post-intervention was significantly lower in the observation group than in the control group [(9.84 ± 1.56) points vs. (12.32 ± 1.62) points, t = 7.39, P < 0.05). The scores of social function, material well-being, physical function, and psychological function post-intervention in the observation group were (59.98 ± 5.31) points, (34.23 ± 4.12) points, (56.87 ± 5.32) points, and (47.28 ± 5.65) points, which were significantly higher than those in the control group [(45.23 ± 6.57) points, (27.98 ± 2.65) points, (43.24 ± 4.53) points, (36.21 ± 4.12) points, t = 11.71, 8.55, 13.08, 10.62, all P < 0.05]. Conclusion:rTMS combined with health education is highly effective on refractory depression. The combined therapy can improve cognitive function and sleep quality and is of great innovation and science.

Effect of different glucose concentrations on the uptake of 18F-FDG in non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the effect of different glucose concentrations on the uptake of 18F-FDG and the expression of glucose transport protein(Glut)-1 and Glut-3 in non-small cell lung cancer (NSCLC). Methods:NSCLC cell line A549 cells were cultured in DMEM medium with glucose concentrations of 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L respectively for 24 h. Then 3.7×10 4 Bq 18F-FDG was added into each group and γ counter was used to measure the radioactivity count 1 h later. Western blot was used to examine the expression of Glut-1 and Glut-3. One-way analysis of variance and Bonferroni test were used for data analysis. The correlation was analyzed by Pearson correlation analysis. Results:The 18F-FDG uptake rates in 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L groups were (4.89±0.83)%, (4.07±0.23)%, (3.66±0.29)%, (3.34±0.16)% and (3.29±0.24)%, respectively ( F=7.05, P=0.006). Compared with 3.9 mmol/L group, the 18F-FDG uptake rates in 8.3 and 11.1 mmol/L groups were reduced and differences were statistically significant ( P values: 0.013, 0.010), while there were no statistical differences between the other groups ( P values: 0.057-0.999). The relative expressions of Glut-1 and Glut-3 in each group were 1.17±0.10, 1.00±0.00, 0.84±0.07, 0.70±0.18, 0.61±0.16, and 1.14±0.05, 1.00±0.00, 0.86±0.12, 0.71±0.05, 0.40±0.06, respectively ( F values: 10.26 and 51.94, P values: 0.001, <0.001). Moreover, the 18F-FDG uptake rates were positively correlated with the expression of Glut-1 and Glut-3 ( r values: 0.775 and 0.744, both P=0.001). Conclusions:When the glucose concentration fluctuates within 3.9-11.1 mmol/L, the change of glucose will affect the 18F-FDG uptake rate and the expression of Glut-1 and Glut-3 in A549 cells. Moreover, the 18F-FDG uptake rate is related to the expressions of Glut-1 and Glut-3.

Exploration of complement-dependent cytotoxicity technology for GTKO/hCD55 genetically engineered pig-to-human xenotransplantation / 中华器官移植杂志

Objective:To compare the inhibitory effect of human CD55(hCD55)expressed on porcine peripheral blood mononuclear cells(PBMC)on rabbit complement-and human complement-dependent cytotoxicity(CDC).Methods:Three α1, 3-galactosyltransferase gene knockout(GTKO)pigs from the same strain were selected.Two were transferred with hCD55 gene.According to the expression level of hCD55, the animals were divided into three groups of GTKO, GTKO/hCD55 Low(low-expression of hCD55)and GTKO/hCD55 High(high-expression of hCD55). After PBMC from these pigs were incubated with complement-inactivated pooled human serum(20 cases), rabbit complement-or human complement-dependent cytotoxicity and binding of antibodies(IgM/G)to pig PBMC were detected by flow cytometry. Results:No significant difference existed in binding of human serum xenoreactive antibodies to PBMC from three groups.The cytotoxicity to GTKO pig PBMC mediated by rabbit complement or human complement were 98.97%±0.50% and 82.73%±3.20% respectively.Both values were quite high.Compared with GTKO group, a low expression of hCD55 had no significant inhibitory effect on rabbit complement-dependent cytotoxicity(97.07%±2.25% vs. 98.9%±0.50%, P=0.2 267) while a high expression of hCD55 exerted a mild inhibitory effect on rabbit complement-dependent cytotoxicity(81.70%±5.86% vs. 98.9%±0.50%, P=0.0 355). Differently, a low expression of hCD55 had a potent inhibitory effect on human complement-dependent cytotoxicity(23.83%±3.53% vs. 82.73%±3.20%, P<0.0 001). Compared with hCD55 low-expression group, a high expression of hCD55 had a further inhibitory effect on human complement-dependent cytotoxicity(2.79%±0.45% vs. 82.73%±3.20%, P=0.009), attaining the level of negative control group.The inhibitory effect of low/high expression of hCD55 on human complement-mediated CDC was significantly better than that on rabbit complement-mediated CDC. Conclusions:Compared with traditional CDC counterpart using rabbit complement, modified CDC technology of commercial standard human complement is recommended for evaluating the regulatory effect of hCD55 expressed on cell surface from GTKO/hCD55 genetically engineered pigs.It thus provides experimental rationales for establishing a novel CDC experimental system of effectively evaluate the function of hCD55 after xenotransplantation.

Clinical application of serum Golgi protein 73 in patients with chronic liver diseases / 中华肝脏病杂志

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period.@*METHODS@#A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated.@*RESULTS@#After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%.@*CONCLUSION@#The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.