[Clinicopathological and molecular characteristics of esophageal carcinoma with ductal differentiation: analysis of 17 cases].

Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34ßE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.

[Construction and analysis of competitive endogenous RNA regulatory network related to gastric cancer].

Objective: To construct the competitive endogenous RNA (ceRNA) network related to gastric cancer and explore the molecular mechanism. Methods: The expression profiles of lncRNA, miRNA and mRNA in gastric cancer and paracancer tissues were analyzed by biochip technology, edgeR package in R software was used to filtrate differential expression genes (multiple change of >1.5 times, P<0.05) and volcano map was drawn. Based on the online miRNA-lncRNA prediction tool lncBase database and the miRNA Target gene prediction database (miRTarBase, target-scan, miRDB, starBase), the relationship between miRNA, lncRNA and mRNA was predicted. Cytoscape software was used to construct lncRNA-miRNA-mRNA ceRNA network and key genes (hub genes) were identified based on cytohubba calculation of degree score of each node. Then Hub genes related to the prognosis of gastric cancer were verified in the TCGA database. The GO and KEGG enrichment analysis of differentially expressed mRNA was performed using the online biological information annotation database DAVID, P<0.05 and false discovery rate (FDR)<0.05 were used as cut-off criteria. R software was used to download the RNA sequencing data and mirna-seq data of gastric cancer and adjacent tissues in TCGA database, edgeR package was used to screen out differentially expressed mRNA, miRNA and lncRNA, and some differentially expressed genes in our data were verified. In OncoLnc database, STAD project of TCGA data was selected and hub gene was input. Patients were divided into two groups based on the median value for hub genes and Kaplan-meier analysis was performed. Results: The differentially expressed 766 mRNA, 110 lncRNA and 10 miRNA were screened out, among them 90 mRNA, 4 lncRNA and 6 miRNA were used to construct the ceRNA network, and 2 of the 20 hub genes were related to the prognosis of patients. MLK7-AS1, SPP1, SULF1, hsa-miR-1307-3p were upregulated in gastric cancer tissues from our biochip, while MT2A, MT1X were downregulated, which were consistent with the results of TCGA gastric cancer database. The differentially expressed mRNAs were significantly enriched in the biological process (BP) and the mineral absorption pathway. CHST1 was negatively correlated while miR-183-5p was positively corelated with the survival of patients. Conclusion: The establishment of ceRNA network for gastric cancer is conducive to further understanding of the molecular biological mechanism. CHST1 and miR-183-5p can be used as prognostic factors of gastric cancer.

[Comparison between minimally invasive surgery and traditional laminectomy in the resection of schwannoma of lumbar vertebra].

Objective: To explore the application, advantages and disadvantages of minimally invasive surgery for lumbar schwannoma. Methods: this study was a prospective, non-randomized controlled study with a trial group (minimally invasive surgery group) and a control group (traditional laminectomy group).For the patients with lumbar schwannoma hospitalized in the neurosurgical spinal ward of Beijing Tian Tan hospital, the surgeon communicated with them one-on-one to inform the patients of the advantages and disadvantages of minimally invasive surgery through channels and traditional laminectomy. After the surgical risks and their respective advantages and disadvantages were identified, patients who underwent minimally invasive surgery to remove tumors through the channel were admitted to the channel surgery group according to the wishes of the patients; otherwise, patients who underwent traditional laminectomy were included in the control group. From December 2017 to March 2019, a total of 15 patients (experimental group) were treated with minimally invasive surgery. A total of 15 patients with tumors similar in size and location to those in the experimental group were selected from the control group who were hospitalized during the same period for traditional laminectomy. Relevant clinical data of the two groups of patients were collected and analyzed, including preoperative lesion imaging characteristics, intraoperative blood loss, operation time, postoperative hospital stay, postoperative complications, symptom improvement, etc. Results: the operating time of the experimental group and the control group was (157±27) min and (158±29) min, respectively (P=0.897). Intraoperative blood loss was (66±27) ml and (110±43) ml, respectively (P=0.020). The mean hospital stay was (7.60±1.29) days and (11.67±1.23) days, respectively (P=0.000). Postoperative JOA scores were 26.73±2.84 and 26.60±2.41, respectively (P=0.891). Postoperative VAS scores were 0.40±1.12 and 0.27±0.71, respectively (P=0.699).The mean blood loss and hospital stay in the experimental group were significantly lower than those in the control group, the difference in operation time between the two groups was not significant, and there was no difference in neurological function results. Conclusion: In certain types of lumbar schwannoma tumors (non-giant tumors), minimally invasive resection through channels has the advantages of less surgical trauma, less bleeding, faster recovery and definite curative effect, which is a safe and effective surgical treatment.

[Genetic characteristic of hemagglutinin of avian influenza A (H7N9) virus in Guizhou Province in 2017].

The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.

Antidamping-Torque-Induced Switching in Biaxial Antiferromagnetic Insulators.

We investigate the current-induced switching of the Néel order in NiO(001)/Pt heterostructures, which is manifested electrically via the spin Hall magnetoresistance. Significant reversible changes in the longitudinal and transverse resistances are found at room temperature for a current threshold lying in the range of 10^{7} A/cm^{2}. The order-parameter switching is ascribed to the antiferromagnetic dynamics triggered by the (current-induced) antidamping torque, which orients the Néel order towards the direction of the writing current. This is in stark contrast to the case of antiferromagnets such as Mn_{2}Au and CuMnAs, where fieldlike torques induced by the Edelstein effect drive the Néel switching, therefore resulting in an orthogonal alignment between the Néel order and the writing current. Our findings can be readily generalized to other biaxial antiferromagnets, providing broad opportunities for all-electrical writing and readout in antiferromagnetic spintronics.

[Dosimetric analysis of volumetric modulated arc therapy and intensity modulated radiotherapy for patients undergone breast-conserving operation].

OBJECTIVE: To compare the dosimetric differences between volumetric modulated arc therapy and intensity modulated radiotherapy for breast cancer patients after breast-conserving surgery. METHODS: Ten patients who received radiotherapy after breast-conserving surgery were selected. Eclipse planning system was used to design volumetric rotating intensity-modulated (2F-RapidArc) and two field intensity-modulated radiation therapy (2F-IMRT) planning for each patient. 2F-RapidArc plans were made using two partial arcs with gantry rotation from 287°-293° to 152°-162°, and 0° to 90 ° was avoidance sector. The gantry angle of 2F-IMRT were 301°-311° and 125°-135°. The prescription dose was 46 Gy/23 fractions. All plans required 95% of the target volume receiving the prescription dose. The dose distribution of the target, organs at risk, machine unit (MU) and treatment time were compared. RESULTS: 2F-RapidArc and 2F-IMRT plans' uniformity index was 1.12±0.02 and 1.11±0.03 (P=0.282), respectively; conformal index was 0.80±0.03 and 0.65±0.04 (P<0.001), respectively. V110 of plan target volume was 20.98%±14.47% and 10.43%±10.49% (P=0.030), respectively. Compared with the 2F-IMRT, 2F-RapidArc plans had a higher dosimetric parameters for left lung: V5 (48.06%±17.32% vs. 24.23%±6.56%,P=0.001), V10 (28.89±9.28 vs.17.07±4.78%,P=0.004), Dmean [(9.70±2.14) Gy vs. (6.86±1.77) Gy, P=0.002], increased the double lung: V5 (22.85%±7.55% vs. 11.01%± 2.95%,P=0.001), V10 (13.16%±4.33% vs. 7.76%± 2.16%, P=0.006), Dmean [(4.66±0.95) Gy vs. (3.17±0.82) Gy, P=0.001], reduced the left lung: V40 (3.58%±1.46% vs. 6.19%±3.04%, P=0.006), reduced the double lung: V40 (1.61%±0.64% vs. 2.81%± 1.39%,P=0.005), increased cardiac: V5 (39.3%±17.19% vs. 8.79%±4.24%, P<0.001), V10 (21.31%±13.8% vs. 5.73%±3.42%, P=0.002), V20 (7.80%±6.08% vs. 4.05%±2.85%,P=0.018), Dmean [(0.64±0.25) Gy vs. (0.29±1.39) Gy,P<0.001],reduced the heart: V40(0.50%±0.40% vs. 1.86%±1.94%,P=0.037),increased the contralateral breast Dmean [(1.63±1.26) Gy vs. (0.09±0.05) Gy, P=0.004]. Compared with 2F-IMRTplan, 2F-RapidArc increased the treatment time [(132.9±7.2) s vs. (140.3±11.6) s, P=0.030]. Both the machine units were almost the same [(467.0±30.4) MU vs. (494.7±44.9) MU, P=0.094]. CONCLUSION: Both 2F-RapidArc and 2F-IMRT plans could reach the clinical requirements. 2F-RapidArc had a better conformal index, reduced the high dose area, but increased the low dose regions of the lung, heart, body area, and increased the average dose of the contralateral breast. The treatment time of 2F-RapidArc was longer than that of 2F-IMRT, and the MU of 2F-RapidArc and 2F-IMRT plans were almost the same.

[Efficacy of Pipeline embolization device in the treatment of large and giant intracranial aneurysms].

Objective: To summarize the safety and efficacy of Pipeline embolization device in the treatment of large and giant intracranial aneurysms (maximum diameter ≥ 10 mm). Methods: The clinical and imaging data of 22 patients with intracranial aneurysms treated by Pipeline Embolization Device (PED) from February 2015 to July 2016 in the Zhengzhou University People's Hospital were retrospectively analyzed. The results about postoperative clinical and imaging follow-up and complications were evaluated. Results: The PED were successfully implanted in 22 patients with 22 intracranial aneurysms. Two aneurysms were treated with PED alone, and 20 aneurysms were treated with PED assisted coil embolization. Perioperative complications occurred in 3 patients (13.6%), and 1 patient died because aneurysm ruptured 3 days after operation. Nineteen patients (19 aneurysms) obtain imaging follow-up visit 3-17 months after operation, 13 of the 19 aneurysms (68.4%) received complete and subtotal occlusion, with no aneurysm recurrence. Eighteen patients obtain clinical follow-up visit 16-32 months after operation, with mRS (modified Rankin scale) score 1 in 5 patients, mRS score 0 in 13 patients, none developed new neurologic symptoms. Conclusions: PED has showed the high rate of obliteration for the treatment of large and giant intracranial aneurysms. But the complications needs to be further studied.

[Analysis of the therapeutic effect of stent-assisted embolization and surgical clipping for the treatment of middle cerebral artery bifurcation aneurysms].

Objective: To compare the clinical effects of stent-assisted embolization and surgical clipping in the treatment of middle cerebral artery bifurcation wide-necked aneurysms. Methods: From July 2014 to March 2017, the clinical and imaging data of 45 patients with Hunt-Hess 0-Ⅲ grade middle cerebral artery bifurcation wide-necked aneurysms were divided into stent-assisted embolization group (20 patients from PLA Rocktet Army Hospital) and surgical clipping group (25 patients from Peking University International Hospital). The total occlusion rates of aneurysm, operation-related adverse events, clinical outcomes, and results of follow-up imaging from the two groups were compared. Results: The total occlusion rates in the stent-assisted embolization group and surgical clipping group were 90.0% (18/20) and 92.0% (23/25), respectively, and the difference was not statistically significant (P=0.815). The favorable six-month postoperative outcomes defined as the modified Rankin Scale ≤2 were 94.7% (18/19) in the stent-assisted embolization group and 91.3% (21/23) in the surgical clipping group (P=0.667). Fewer patients experienced the operation-related adverse events in the stent-assisted embolization group (15.0%, 3/20), as compared to that of the surgical clipping group (24.0%, 6/25), but the difference were not significant (P=0.453). After 2-24 months (median 7 months) of the operation, the follow-up imaging indicated that in the stent-assisted embolization group, 2 out of the 19 patients had residual or recurrent aneurysms.While in the surgical clipping group, residual or recurrent aneurysms were identified in 2 out of the 23 patients 2-14 months (median 3 months) after the surgery; the frequency was not statistically different between the two groups (P=0.841). Conclusion: Stent assisted embolization is a safe and effective treatment for the low grade middle cerebral artery bifurcation wide-necked aneurysms.

[Efficacy and dosimetric analysis of (125)I seeds implantation for pelvic recurrent cervical cancer after radiotherapy under CT guidance].

Objective: To evaluate the relationship of dosimetry parameters and efficacy of (125)I seeds implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy(EBRT) under CT guidance. Methods: A retrospective analysis was made on 30 PRCC patients after EBRT in Peking University Third Hospital with (125)I seeds implantation under CT guidance. Postoperative plans were made to evaluate the dosimetric parameters. Kaplan-Meier method was used to calculate local progression free survival (LPFS) rate and overall survival (OS) rate, and Log-rank test and Cox regression were used for univariate and multivariate analysis. Results: The 1-year and 2-year LPFS rate was 39.4% and 22.5%, respectively. The 1-year and 2-year OS rate was 57.3% and 27.4%, respectively. On postoperative plan, D(90) was (132±47) Gy, D(100) was (51±24) Gy, V(100) was 88%±10%, V(150)was 69%±15%, V(200) was 51%±18%.LPFS time would be longer while D(90) ≥105 Gy or D(100) ≥ 55 Gy or V(100) ≥ 91% (all P<0.05). D(100) was significantly related to LPFS (P<0.05). But these dosimetry parameters got no effect on OS. Conclusions: LPFS time of (125)I seeds implantation for PRCC after EBRT under CT guidance would be longer when D(90)≥105 Gy or D(100)≥ 55 Gy, or V(100)≥ 91%. D(100) is an independent factor related to LPFS.

[Interventional treatment of symptomatic intracranial in-stent restenosis].

Objective: To assess the feasibility and safety of interventional treatment of symptomatic intracranial in-stent restenosis (SISR). Methods: Clinical data of 21 patients with SISR who underwent interventional treatment in the General Hospital of the PLA Rocket Force from January 2012 to May 2018 were retrospectively analyzed. Perioperative complications, angiographic and clinical follow-up results were recorded. Results: The success rate of treatment was 100%, including 21 lesions of SISR (7 at the V4 segment of the vertebral artery, 7 at the basilar artery, 5 at the M1 segment of middle cerebral artery, 2 at the internal carotid artery). The residual stenosis rate was preoperative 84±7, postoperative 30±14 respectively. Balloon angioplasty and stent implantation were performed in 10 patients (48.6%) and 11 patients (52.4%), respectively. After treatment, 1 patient experienced perforating event without neurological sequelae. Of the 11 patients (52.4%) completed angiography follow-up, 3 (3/11, 27.3%) ocurred restenosis and 1 was retreated. During clinical follow-up, 1 patients received intravenous thrombolysis for the symptom of acute cerebral infarction in territory of stenting artery, in-stent restenosis or occlusion was not demonstrated by emergency cerebral angiography. Conclusion: Interventional treatment of SISR is feasible and safe, however, further studies need to warrant the long-term effects.

[Hybrid surgery for complex symptomatic intracranial fistulas: a technical note].

Objective: To explore the efficacy of hybrid management of complex symptomatic intracranial fistulas in neurovascular hybrid operating room. Methods: From March 2014 to January 2015, 2 complex dural arteriovenous fistulas and 1 carotid cavernous fistulas were managed by hybrid surgeries in the PLA Rocket Force General Hospital.With first attempts with endovascular treatment failed, all cases were finally managed by hybrid surgery.Dural arteriovenous fistulas were approached via meningeal artery followed craniotomy.The carotid cavernous fistulas were treated by direct puncture into the left cavernous sinus after craniotomy. Results: Post-operative angiography demonstrated complete occlusion for 2 cases and nearly complete occlusion for 1 case.All 3 cases had no complications.On discharge 2 patients presented no symptoms and 1 greatly improved.Within the follow-up (1-33 months), 1 patient had recurrence after 21 months and received re-embolization with complete occlusion. Conclusion: Hybrid surgery is a promising method to manage complex intracranial fistulas.

[Retrospective analysis of the discharge outcome of external ventricular drainage and conservative treatment in patients with severe intraventricular hemorrhage].

Objective: To investigate the discharge outcome of external ventricular drainage(EVD) and conservative treatment in patients with severe intraventricular hemorrhage (SeIVH). Methods: From January 2011 to December 2016, patients with SeIVH admitted to the General Hospital of the PLA Rocket Force and the Army General Hospital received EVD treatment and were classified as the treatment group. According to intraventricular hemorrhage volume and age, patients received conservative treatment were pair matched and classified as control group. Then we compared the clinical outcome of moderate disability or less degree of discharge (mRS ≤3) and death incidence (mRS 6) between two groups. Results: A total of 361 patients with IVH were treated during these six years. Among them, 75 cases were chosen as treatment group. Another 75 cases were pair matched as control group from 286 cases. At the time of admission, the ventricular hemorrhage volume of two groups were (55.8±22.7) ml and (53.7±23.3) ml (P=0.569) respectively. Cerebral hemorrhage volume were (23.6±5.3) ml and (24.0±5.4) ml (P=0.631). And the median Glasgow coma score (GCS) were 4[IQR(3, 7)] and 5[IQR(4, 7)](P=0.131). At the discharge time, there were 16% (12/75) patients scored mRS≤3 in treatment group, while 2.7% (2/75) in control group (P<0.005). The absolute risk reduction (ARR) was 13.3%, and the number needed to treat (NNT) was 7.5. The mortality rate of treatment group was 13.3% (10/75), much lower than that of the control group 41.1% (31/75, P<0.001). ARR was 27.8% and NNT was 3.6. Conclusion: Although the prognosis of SeIVH was poor, compared with conservative treatment, EVD treatment significantly improved the outcome of these patients. Randomized controlled trials are needed to validate the efficacy of EVD.

Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune thyroid diseases.

Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster. Genotyping of these SNPs was performed using matrix-assisted laser desorption / ionization-time-of-flight mass spectrometer (MALDI-TOF-MS) platform from Sequenom. The frequencies of allele A and AA+AG genotype of rs6543116 (ST2) in HT patients were significantly increased compared with those of the controls (P = 0.029/0.021, OR = 1.31/1.62). And in another SNP rs917997, AA+AG genotype presented an increased frequency in HT subjects compared with controls (P = 0.046, OR = 1.53). Furthermore, the haplotype GAGCCCG from ST2-IL18R1-IL18RAP gene cluster (rs6543116, rs1041973, rs1035130, rs3732127, rs1035127, rs2293225, rs917997) was associated with increased susceptibility to GD with an OR of 2.03 (P = 0.022, 95% CI = 1.07-3.86). Some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of HT and GD in Chinese Han population.

[Application of (125)I seeds combined with biliary stent implantation in the treatment of malignant obstructive jaundice].

OBJECTIVE: To study the feasibility and therapeutic effect of the application of (125)I seeds combined with biliary stent implantation on the treatment of malignant obstructive jaundice. METHODS: Fifty patients with malignant obstructive jaundice treated from September 2010 to February 2013 in Yantai Yuhuangding Hospital were included in this study. Among them, 24 patients received biliary stent implantation combined with (125)I seeds intraluminal brachytherapy as experimental group, and 26 were treated by biliary stent implantation as control group.The total bilirubin, direct bilirubin and tumor markers (CA-199, CA-242, CEA) before and after surgery, the biliary stent patency status was assessed, and the survival time was evaluated. RESULTS: The 24 patients in experimental group were implanted with 30 (125)I seeds successfully in a total of 450 seeds. Jaundice was improved greatly in both groups. The CA-199 and CA-242 after treatment in the experimental group were significantly decreased than that before treatment (P=0.003 and P=0.004). CEA was also decreased, but showed no statistical significance (P>0.05). There were no significant improvement comparing the CA-199, CA-242 and CEA before and 2 months after surgery in the control group (P>0.05). The rate of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (P=0.048). The mean biliary stent patency time in the experimental group was 9.84 months (range 1-15.5 months). The mean biliary stent patency time in the control group was 5.57 months (range 0.8-9 months). There was a significant difference between the two groups (P=0.018). The median survival time was 10.2 months in the experimental group and 5.4 months in the control group (P<0.05). CONCLUSION: (125)I seeds combined with biliary stent implantation can inhibit the proliferation of vascular endothelial cells and the growth of tumor effectively, and can prolong the biliary stent patency time and the survival time obviously for patients with malignant obstructive jaundice, therefore, is a safe and effective treatment in this malignancy.

[Effect of traditional Chinese medicine treatment as maintenance therapy on regulating the serum concentration of sCTLA-4 in patients with advanced non-small-cell lung cancer and its relationship with prognosis].

Objective: To evaluate the effect of traditional Chinese medicine (TCM) treatment as maintenance therapy on regulating the serum concentration of soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in patients with advanced non-small-cell lung cancer (NSCLC) and the relationship between sCTLA-4 and time to progression (TTP). Methods: This study was conducted as a prospective, randomized, controlled trial. 64 non-progressive patients who responded to initial therapy were randomized 1∶1 to the TCM arm (treated with cinobufacini injection, herbal decoction and Chinese acupoint application, n=32) or to the chemotherapy arm (n=32). Each cycle was 21 days. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient requested therapy discontinuation.The serum concentration of sCTLA-4 was detected by enzyme linked immunosorbent assay (ELISA) in the 64 patients with advanced NSCLC before and after two cycles of maintenance treatment. Cox regression was used to analyze the relative ratio for the risk of disease progression. Results: After 2 cycles of maintenance TCM treatment, the serum concentration of sCTLA-4 in patients with advanced NSCLC was (12.77±2.37 pg/ml), significantly lower than that before treatment (40.30±10.75)(P=0.013). After 2 cycles of maintenance chemotherapy, the serum concentration of sCTLA-4 was higher than that before treatment, but was not significantly different (44.48±10.12 vs. 46.64±11.21 pg/ml, P=0.612). After 2 cycles of maintenance treatment, TCM treatment can significantly bring down the serum concentration of sCTLA-4 compared to chemotherapy (12.77±2.37 vs. 46.64±11.21 pg/ml, P=0.004). The multivariate analysis indicated that sCTLA-4 levels and treatment regimen were independent prognostic factors for TTP (P<0.05 for both). Conclusions: Regulating the serum concentration of sCTLA-4 may be one of the mechanisms of TCM maintenance treatment of NSCLC. Trial registration Chinese Clinical Trial Register, ChiCTR-TRC-10001017.

[Management of 99 intracranial aneurysms in neurovascular hybrid operating room].

OBJECTIVE: To analyze the current status of intracranial aneurysms treated in neurovascular hybrid operating room. METHODS: In the neurovascular hybrid operating room of New Era Stroke Care & Research Center, the Second Artillery General Hospital PLA, from October 2013 to November 2015, 99 cases of intracranial aneurysms were managed by interventional treatment, open surgery, hybrid surgery or switched surgical procedures. RESULTS: Patients with intracranial aneurysms treated in neurovascular hybrid operating room achieved good clinical outcome. CONCLUSION: It is an ideal option to treat intracranial aneurysms in neurovascular hybrid operating room.

[Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Identification of new subtypes and potential genetic signatures in triple-negative breast cancer using weighted gene co-expression network analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Here, we used gene expression profiling to define new subtypes of TNBC, which may improve prevention and treatment through personalized medicine. MATERIALS AND METHODS: Gene expression profiles from the public datasets GSE76250, GSE61724, GSE61723, and GES76275 were subjected to co-expression analysis to identify differentially expressed genes (DEGs) between TNBC and non-TNBC tissues. Consistency clustering was used to define TNBC subtypes, whose correlation with gene modules was analyzed. Enrichment analysis was used to identify module genes' biological functions and pathways. Single-sample gene set enrichment analysis was used to assess immune cell infiltration in the different TNBC subtypes, and the ChAMP package was used to examine methylation sites in TNBC. RESULTS: A total of 4,958 DEGs in TNBC were identified, which showed the same expression differences across all datasets as in the dataset GSE76250 and clustered into 9 co-expression modules. TNBC samples clustered into two subtypes based on nine hub genes from the modules. Class I showed the most significant correlation with module 1, whose genes were related mainly to interleukin-1 response, while class II showed the most significant correlation with module 6, whose genes were related mainly to the transforming growth factor-ß pathway. Class I was significantly enriched in cell cycle and DNA replication, and tumors of this subtype showed lower immune cell infiltration than class II tumors. Tumor infiltration by Th2 cells correlated positively with the expression of MCM10 and negatively with the expression of PREX2. A greater methylation of CIDEC, DLC1, EDNRB, EGR2 and SRPK1 correlated with better prognosis. CONCLUSIONS: Class I TNBC, for which a useful biomarker is MCM10, may be associated with a worse prognosis than class II TNBC, for which PREX2 may serve as a biomarker.

[Analysis of risk factors and prognosis of cytomegalovirus infection post umbilical cord blood stem cell transplantation in children with primary immunodeficiency diseases].

Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×106 vs. 22.5 (13.2, 31.9)×106 copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×106 vs. 28.4 (24.1, 53.5)×106copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×106 vs. 25.9 (14.2, 12.2)×106copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×106 vs. 27.7 (19.7,51.8)×106copies/L, Z=-1.49, P=0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ2=4.76, P<0.05). The rate of CMV-seropositive recipients and Ⅱ-Ⅳ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ2=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ2=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ2=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ2=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4+ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×106 vs. 175.5 (108.3, 257.2) ×106/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8+T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade Ⅱ-Ⅳ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.