Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.
Humans ; Male ; B7-H1 Antigen/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Lung Neoplasms/pathology* ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; Female

OBJECTIVE: To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI). METHODS: Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function. RESULTS: Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05). CONCLUSION cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.
Female ; Animals ; Rats ; Rats, Sprague-Dawley ; Neuroprotective Agents/pharmacology* ; Spinal Cord Injuries/drug therapy* ; Spinal Cord Compression

Objective To investigate the factors affecting the dose distribution to the tumor target volume(GTV)and normal tissues in cerebral arteriovenous malformation(AVM)treated with CyberKnife,and to analyze the effect of collimators of different diameters on the dose distribution of cerebral AVM,so as to provide references for cerebral AVM CyberKnife treatment plans.Methods Totally 12 cerebral AVM patients receiving CyberKnife treatment after embolization in some hospital between 2015 and 2020 were selected.Collimators were determined according to 30％,40％,50％,30％+40％+50％of the GTV cross-sectional long diameters,and four different treatment plans were developed for each patient and then enrolled into Group A,Group B,Group C,and Group D,respectively.The effects of the shape and volume of GTV and the size of collimator on the dose distribution in the target area were analyzed,and the dose fall-off outside the target area was investigated.SPSS 20.0 software was used for statistical analysis.Results The effects of width,height,volume and regularity of GTV on the conformity index(CI),new conformity index(nCI),geometric conformity index(gCI)and number of beams were statistically significant(P＜0.05).When compared with group A,B and D,group C had the minimum dose,median absorbed dose,target area coverage,target gradient index and prescription dose line of GTV increased while the CI,nCI,gCI of GTV and the number of monitor units,treatment nodes and beams decreased significantly(P＜0.05).In group C median absorbed dose of normal tissue more than 20 mm apart from the target area decreased,while median absorbed dose of normal tissue not longer than 15 mm apart from the target area increased.Conclusion During CyberKnife treatment of cerebral AVMs,collimator selection based on 50％of the GTV cross-sectional long diameter can achieve an optimal dose distribution while improving the efficiency of the execution of the CyberKnife treatment plan.[Chinese Medical Equipment Journal,2023,44(11):56-60]

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.
Acute Disease ; Burkitt Lymphoma ; Child ; Gene Deletion ; Humans ; Ikaros Transcription Factor/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis

Objective: To explore the establishment of an efficient and automatic method to determine anatomical landmarks in three-dimensional (3D) facial data, and to evaluate the effectiveness of this method in determining landmarks. Methods: A total of 30 male patients with tooth defect or dentition defect (with good facial symmetry) who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to August 2021 were selected, and these participants' age was between 18-45 years. 3D facial data of patients was collected and the size normalization and overlap alignment were performed based on the Procrustes analysis algorithm. A 3D face average model was built in Geomagic Studio 2013 software, and a 3D face template was built through parametric processing. MeshLab 2020 software was used to determine the serial number information of 32 facial anatomical landmarks (10 midline landmarks and 22 bilateral landmarks). Five male patients with no mandibular deviation and 5 with mild mandibular deviation were selected from the Department of Orthodontics or Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June to August 2021. 3D facial data of patients was collected as test data. Based on the 3D face template and the serial number information of the facial anatomical landmarks, the coordinates of 32 facial anatomical landmarks on the test data were automatically determined with the help of the MeshMonk non-rigid registration algorithm program, as the data for the template method to determine the landmarks. The positions of 32 facial anatomical landmarks on the test data were manually determined by the same attending physician, and the coordinates of the landmarks were recorded as the data for determining landmarks by the expert method. Calculated the distance value of the coordinates of facial anatomical landmarks between the template method and the expert method, as the landmark localization error, and evaluated the effect of the template method in determining the landmarks. Results: For 5 patients with no mandibular deviation, the landmark localization error of all facial anatomical landmarks by template method was (1.65±1.19) mm, the landmark localization error of the midline facial anatomical landmarks was (1.19±0.45) mm, the landmark localization error of bilateral facial anatomical landmarks was (1.85±1.33) mm. For 5 patients with mild mandibular deviation, the landmark localization error of all facial anatomical landmarks by template method was (2.55±2.22) mm, the landmark localization error of the midline facial anatomical landmarks was (1.85±1.13) mm, the landmark localization error of bilateral facial anatomical landmarks was (2.87±2.45) mm. Conclusions: The automatic determination method of facial anatomical landmarks proposed in this study has certain feasibility, and the determination effect of midline facial anatomical landmarks is better than that of bilateral facial anatomical landmarks. The effect of determining facial anatomical landmarks in patients without mandibular deviation is better than that in patients with mild mandibular deviation.
Adolescent ; Adult ; Algorithms ; Anatomic Landmarks ; Cephalometry/methods* ; Face/anatomy & histology* ; Female ; Humans ; Imaging, Three-Dimensional/methods* ; Male ; Malocclusion ; Middle Aged ; Orthodontics ; Software ; Young Adult

OBJECTIVE: To explore the clinical efficacy and safety of manual therapy combined with posterior percutaneous endoscopic cervical decompression(PECD) in the treatment of intractable cervical spondylotic radiculopathy. METHODS: From May 2016 to May 2018, 23 CSR patients who responded poorly to conservative treatment for at least 6 weeks underwent the combination management. Firstly, the patients received the posterior percutaneous endoscopic cervical decompression routine care for the following 4 weeks and manual therapy for another 4 weeks. A total of 23 patients were followed up, including 14 males and 9 females, the age ranged from 29 to 78 years old with an average of (50.30±12.28) years, the course of disease was 3 to 24 months with an average of (9.74±5.76) months. The lesion segment involved C_4,5 in 4 cases, C_5,6 in 13 cases, C_6,7 in 6 cases. The visual analogue scale (VAS), neck disability index (NDI), changes of cervical physiological curvature and interbody stability, adverse events were observed before and after operation. The follow-up time points were before operation, 1 day after operation and 1, 3 and 6 months after operation. RESULTS: All patients successfully completed the operation and manual treatment for 4 to 8 times. Among the 29 cases, 23 patients were followed up for more than 6 months. There was no spinal cord and nerve root injury during the treatment and follow-up. Operation time was from 80 to 120 min with a median of 90 min;intraoperative blood loss was from 35 to 80 ml with a median of 50 ml. NDI, VAS of neck, shoulder and arm each period after operation were significantly lower than those before PECD(P<0.05), while there were no significant improvement in cervical physiological curvature and target segment intervertebral space height(P>0.05);there was no significant change in interbody stability (P>0.05). After received the manual therapy, NDI significantly decreased (P<0.05), however, there was no significant difference in VAS of neck, shoulder and arm, physiological curvature of cervical spine and intervertebral space height of target segment compared with that before manual treatment (P>0.05);there was no significant change in interbody stability (P>0.05). CONCLUSION Manual therapy combined with PECD in the treatment of intractable cervical spondylotic radiculopathy can not only quickly improve the symptoms, but also alleviate the residual symptoms after PECD safely and effectively, and can not cause obvious signs of accelerated instability of cervical adjacent segments in the short term.
Cervical Vertebrae/surgery* ; Child ; Child, Preschool ; Decompression/adverse effects* ; Female ; Humans ; Male ; Musculoskeletal Manipulations ; Radiculopathy/surgery* ; Retrospective Studies ; Spondylosis/surgery* ; Treatment Outcome

Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.