Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.

Tryptophan metabolism plays an important role in immunometabolism in sepsis,and the expression of indoleamine 2,3-dioxygenase 1(IDO1),the key enzyme of tryptophan metabolism,is up-regulated during sepsis.This study was designed to construct IDO1 gene knockout THP-1 cell line using CRISPR/Cas9,and to provide a cell model for studying the role of IDO1 in macrophage function.Three gRNAs were designed for the IDO1 gene,and inserted into YKO-Lentiviral gRNA plasmid respectively to construct IDO1-gRNA recombinant plasmid,which then confirmed by restriction enzyme digestion and sequencing,and packaged as Lenti-IDO1-gRNA lentivirus.THP-1 cells were infected with Cas9 lentivirus to construct a THP-1 Cas9 cell line stably expressing Cas9 protein.Then THP-1 Cas9 cells were infected with the Lenti-IDO1-gRNA lentivirus for IDO1 gene knockout,and the monoclonal cell lines were screened by limited dilution method.The efficiency of IDO1 knockout was identified by T7E1 digestion test,PCR product sequencing and Western blotting.The proliferative activity of THP-1 cells was detected by CCK8 assay;the expression of CD11b,CD68 and CD 14 in THP-1 macrophages were detected by flow cytometry;and the phagocytic function of THP-1 macrophages was detected by neutral phagocytosis test.T7E1 restriction enzyme digestion results showed that all the three gRNAs could effectively edit IDO1 gene,and gRNA2 had the highest editing efficiency.Sequencing of PCR products showed that IDO1 gene was mutated in three THP-1 IDO 1-KO monoclonal cell lines,and Western blot result showed that IDO1 protein was not expressed,suggesting THP-1 IDO1-KO cells were successfully constructed.CCK-8 proliferation assay showed that IDO1 gene knockout could inhibit the proliferation of THP-1 cells.Flow cytometry showed that IDO1 gene knockout down-regulated the expression of CD1 1b and CD68 in THP-1 macrophages,while up-regulated the expression of CD 14.The results of neutral red phagocytosis test showed that IDO1 gene knockout promoted the phagocytosis of macrophages.In conclusion,the IDO1 gene knockout THP-1 cell line has successfully constructed by CRISPR-Cas9,and IDO1 plays an important role in regulating the proliferation activity and differentiation of THP-1 cells,as well as the phagocytic function of THP-1 macrophages.

This report describs 2 domestic cases of tacrolimus poisoning in kidney transplant recipients due to overexposure of tacrolimus caused by nirmatrelvir/ritonavir for SARS-CoV-2 infection.Phenytoin sodium is prescribed for inducing CYP3A enzyme.It is intended for providing references for formulating and adjusting treatment protocols for tacrolimus overexposure and related toxicity in kidney transplant recipients caused by nirmatrelvir/ritonavir.

Objective:To explore the safety and effectiveness of medium-frequency electrotherapy for increasing the volume of the latissimus dorsi muscle.Methods:Fifteen adult New Zealand white rabbits were randomly divided into three groups, namely group A, group B, and group C, with 5 rabbits in each group. This was a self-control study, with the right latissimus dorsi muscle as the experimental group and the left latissimus dorsi muscle as the control group. The three groups corresponded to three different current intensity levels: 7.062 mA for group A (6th gear), 10.593 mA for group B (9th gear), and 14.124 mA for group C (12th gear). After the 12th, 24th, and 36th sessions of the experiment, ultrasonography was used to collect the thickness of the latissimus dorsi muscle. After the 36th electrostimulation, the latissimus dorsi muscle samples were collected to measure their in vivo muscle thickness and wet weight and were then sent for HE and MASSON staining.Results:After the 12th, 24th, and 36th electrostimulation sessions, ultrasonographic sampling in groups A and B showed an increase in the thickness of the right latissimus dorsi muscle compared to the left; for example, the thickness on the right of group B increased by 37.8%. The wet weight data collected after the 36th electrostimulation in groups A and B showed an increase in the right latissimus dorsi muscle compared to the left; for example, the wet weight on the right of group B increased by 5.04%.Conclusions:Different electrostimulation modes of medium-frequency therapy technology can induce muscle fiber thickening or atrophy. In this experiment, the 9th gear (10.593 mA) of medium-frequency therapy technology may be a suitable choice for inducing muscle fiber thickening, and the 12th gear (14.124 mA) may be a suitable choice for inducing skeletal muscle thinning.

Objective To detect the activation levels of endoplasmic reticulum stress ATF6-CHOP pathway,and to investigate the molecular mechanism of tannic acid (TA) combined with cisplatin (CDDP) against hepatocellular carcinoma.Methods HepG2 cells were cultured with 180 μM TA or/and 0.9 μg/ml CDDP for 24 h or 48 h.The levels of ATF6 (ATF6α),ATF6B (ATF6β) and CHOP were analyzed by real-time fluorescence quantitative PCR (q-RT-PCR) and western blot.Results We found that after 24 h or 48 h,compared with the control group,ATF6 mRNA and protein levels,ATF6B protein level,CHOP mRNA and protein levels were significantly increased in the TA group,CDDP group or combination group (P ＜ 0.01 or P ＜ 0.05).Conclusion TA can combine with CDDP to increase the levels of endoplasmic reticulum stress ATF6-CHOP pathway,and the ATF6-CHOP pathway may be one of the molecular mechanisms synergistic anti-hepatocellular carcinoma effect of TA and CDDP on HepG2 cells.

Objective To retrospectively analyze the injury characteristics of victims and treatment strategies in the explosion accident on the 17th May 2018 in Xixia county (Xixia "May 17th" explosion accident). Methods Based on the practice featured in pre-hospital emergency of Henan province and Nanyang city Emergency Center in the explosion accident, a retrospective analysis for the Level Three medical rescue was conducted, where a total of thirteen survived victims in Xixia "May 17" explosion accident were studied retrospectively. The data included the gender, age, burned extent and depth of the patients, burns complicated by trauma, complication of burn, respiratory function maintenance, resuscitation during shock stage, skin grafting with excision and scab. Furthermore, the data of organ function and the effect of the 90-day comprehensive treatment for the burned victims wereanalyzed. Results completion the Level Three treatment on time, which was depended on the leading role played by the regional trauma centers was the main rescuing mode of the work in Xixia county, where the primary and secondary treatments were the key parts. The three-level treatment model includes: the local hospital acts as a level-one emergency medical institution, county hospitals function as secondary emergency medical institutions, and other higher medical institutions are the tertiary first aid medical institutions. The pre-hospital and in-hospital emergency procedures were initiated immediately after the large-scale explosive burn being identified, the key to the successfully rescue was to set up a comprehensive treatment team for burns and trauma. Rescue team should involve burn department and other related departments, including the departments of emergency, general surgery, orthopedic, thoracic surgery, neurosurgery, plastic surgery, intensive care unit, blood transfusion unit, anesthesiology, and interventional radiology, etc. All the thirteen burned patients were male, with inhalation injury, blast injury, hemopneumothorax, brain injury, bone fractures, and etc. Eight of them (61.54%) had multiple organ dysfunction syndrome (MODS). MODS mainly involved respiratory, circulatory, liver, gastrointestinal tract, kidney and coagulation function. With the multi-discipline treatment, the wound of 6 severely-burned patients started healing and can be discharged after keeping the patency of airway, applying resuscitation fluid and comprehensive treatments such as debridement and dressing change. Among 7 patients with extensive deep burns, one case with skull-based fracture, open craniocerebral, extensive intracranial hemorrhage and hemopneumothorax, died 9 hours later. Another case died within 24 hours after injury due to obvious exudation on the site of early incision and relaxation of wound. The escharotomy, micro-dermis and allograft skin transplantation were carried out for five cases with extensive deep burns from the 4th day after the recovery of shock. One week later, the second stage of microsphere skin transplantation was performed. But all died of sepsis or fungal infection. Conclusions MODS and infection often occur during the course especially for patients with extensive and deep burns due to the great explosion in Xixia county, most of whom were accompanied with MODS and infection. Therefore, assembling multi-discipline team for treating the group of explosively-burned patients can increase the survival rate and reduce the possibility of disability.

Objective To investigate the protective effect of a COX inhibitor,flurbiprofen (Flurb) on hepatic ischemia/reperfusion (IR) injury in rats and the action mechanism.Method C57BL/6 mice were randomized into sham,IR and Flurb (4 different doses) groups.The model of segmental (70％) warm hepatic ischemia was established in IR and Flurb groups.Flurbiprofen of different doses (5,7.5,10 and 15 mg/kg) was injected via the tail vein 20 min before ischemia.At different time points after reperfusion,liver cell necrosis and apoptosis were evaluated by HE and TUNEL staining.The COX and inflammatory cytokine gene expression was detected by using realtime PCR.Liver mitochondria were separated and mitochondrial permeability transition (MPT) pore sensitivity was examined by using swelling assay and fluorescence spectrophotometry assay.Result In flurbiprofen groups of different doses,the serum AST and ALT levels were significantly decreased at 6 h after reperfusion as compared with IR group.Moreover,10 mg/kg Flurb pretreatment significantly inhibited the mitochondrial permeability transition (MPT) pore opening,and thus alleviated liver cell damage and prevented mitochondria-related cell death and apoptosis by inhibiting COX-2 and inflammatory factor genes expression such as IL-1β,IL-6 and TNF-α.Conclusion Flurbiprofen protects mice from hepatic I/R injury possibly by inhibiting mitochondrial permeability transition and IL-1β,IL-6 and TNF-α expression,which may provide experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings other than its conventional use for pain relief.

Resident standardization training is an important part of postgraduate medical educa-tion and anesthesiology rotation is an important part in resident standardization training. Anesthesiology rotation is an effective way to improve the efficiency of hospital operation and is an important starting point to promote 'comfortable medical' and hospital upgrades. To improving the quality of training , anes-thesiology department should establish training and supervision system clearly , organize teacher training regularly. Continuous improvements in institutional mechanism can be achieved by detailed theoretical studies, technical operations and departmental rotation examination requirements as well as by exchanging ideas between teachers and students.