[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

New radiofrequency ablation procedure for selective reduction in complicated monochorionic twin or triplet pregnancy using multistep, incremental expansion technique.

OBJECTIVE: Radiofrequency ablation (RFA) is the preferred approach for selective reduction in complex monochorionic (MC) multiple pregnancies owing to the ease of operation and minimal invasiveness. To optimize the RFA technique and reduce the risk of adverse pregnancy outcome resulting from the heat-sink effect of RFA therapy, we used an innovative RFA method, in which an electrode needle was expanded incrementally and stepwise. This study aimed to assess the efficacy and safety profile of this novel multistep incremental expansion RFA method for selective fetal reduction in MC twin and triplet pregnancies. METHODS: This was a single-center retrospective cohort study of all MC multiple pregnancies undergoing RFA between March 2016 and October 2022 at our center. The multistep RFA technique involved the use of an expandable needle, which was gradually expanded during the RFA procedure until cessation of umbilical cord blood flow was achieved. The needle used for the single-step RFA method was fully extended from the start of treatment. RESULTS: In total, 132 MC multiple pregnancies underwent selective reduction using RFA, including 50 cases undergoing multistep RFA and 82 cases undergoing single-step RFA. The overall survival rates were not significantly different between the multistep and single-step RFA groups (81.1% vs 72.3%; P = 0.234). Similarly, the rates of preterm prelabor rupture of the membranes within 2 weeks after RFA, procedure-related complications, spontaneous preterm delivery and pathological findings on cranial ultrasound, as well as gestational age at delivery and birth weight, did not differ between the two groups. However, there was a trend towards a prolonged procedure-to-delivery interval following multistep RFA compared with single-step RFA (median, 109 vs 99 days; P = 0.377). Moreover, the fetal loss rate within 2 weeks after RFA in the multistep RFA group was significantly lower than that in the single-step RFA group (10.0% vs 24.4%; P = 0.041). The median ablation time was shorter (5.3 vs 7.8 min; P < 0.001) and the median ablation energy was lower (10.2 vs 18.0 kJ; P < 0.001) in multistep compared with single-step RFA. There were no significant differences in neonatal outcomes following multistep vs single-step RFA. CONCLUSIONS: Overall survival rates were similar between the two RFA methods. However, the multistep RFA technique was associated with a lower risk of fetal loss within 2 weeks after RFA. The multistep RFA technique required significantly less ablation energy and a shorter ablation time compared with single-step RFA in selective fetal reduction of MC twin and triplet pregnancies. Additionally, there was a trend towards a prolonged procedure-to-delivery interval with the multistep RFA technique. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Analysis of typing conversion and perinatal outcomes in twins with selective intrauterine growth restriction of different subtypes].

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.

[Complicated lymphatic anomaly: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features, clinical manifestations and different diagnosis of patients with complicated lymphatic anomaly. Methods: The clinical and pathologic data of four patients with complicated lymphatic anomaly diagnosed and treated in Peking Union Medical College Hospital from January 2000 to December 2021 were collected and analyzed. Results: One Gorham-Stout disease case and three generalized lymphatic anomaly cases were included in this cohort. Patients' ages ranged from 7 to 32 years. There were three males and one female. The positions of biopsy included three bone biopsy and one bronchus biopsy. Microscopically, all cases showed diffuse enlarged lymphatic channels. At the same time, osteogenesis was obvious in Gorham-Stout disease case. Radiologically, cortical loss was seen in Gorham-Stout disease, and lytic bone confined to the medullary cavity presented in generalized lymphatic anomaly. The three generalized lymphatic anomaly cases also had coagulopathy, and two had effusion. Conclusions: The histologic feature of complicated lymphatic anomaly was diffuse lymphatic malformation, and the diagnosis depends on clinical and pathologic information. The treatment and prognosis of these diseases are different, and therefore it is necessary to understand their clinical and pathologic features and make the correct diagnosis.

[Consideration of diagnosing extremely well differentiated adenocarcinoma of gastrointestinal tract].

For gastrointestinal adenocarcinoma with excellent differentiation, some diagnostic names have emerged in recent years, which have overlapping and different meanings. Low-grade well differentiated adenocarcinoma and very well differentiated adenocarcinoma are terms for a group of adenocarcinomas with good differentiation and little cellular atypia, including a variety of histological types. It is suggested that specific histological types should be listed as far as possible in diagnosis, instead of using "low-grade well differentiated adenocarcinoma" or "very well differentiated adenocarcinoma" as a complete diagnosis. This kind of adenocarcinomas may lack cellular pleomorphism, so it is necessary to observe the structural atypia for diagnosis. At the same time, attention should be paid to the differentiation of reactive changes, low grade dysplasia, epithelial misplacement and other lesions.

[Prenatal diagnosis and prognostic factors analysis of fetal sacrococcygeal teratoma].

Objective: To investigate the prenatal diagnosis and prognostic factors of fetal sacrococcygeal teratoma (SCT). Methods: A retrospective analysis was performed on 41 pregnant women who were diagnosed with fetal SCT by prenatal ultrasound at the Women's Hospital, Zhejiang University School of Medicine from January 2014 to September 2021. The prenatal imaging features and pregnancy outcomes, including tumor volume to fetal weight ratio (TFR), proportion of solid tumor, tumor growth rate (TGR), fetal hydrops, placentomegaly and polyhydramnios were analyzed. Receiver operating characteristic (ROC) curve was used to determine the critical values of TFR and TGR for predicting adverse fetal outcomes. Results: (1) Among the 41 pregnant women with fetal SCT, the diagnostic gestational week of ultrasound was (24.2±2.9) weeks (range: 18-28 weeks). Among them, 1 case progressed to fetal hydrops and induced labor at 22 weeks of gestation, 1 case developed intrauterine death and induced labor at 29 weeks of gestation, and 39 pregnancies continued until delivery. Among the 39 cases of continued pregnancy, 1 case underwent cesarean section at 31 weeks of gestation due to malignant polyhydramnios and increased fetal cardiothoracic ratio in the third trimester, 1 case underwent cesarean section at 32 weeks of gestation due to fetal heart failure, and 1 case underwent cesarean section at 32 weeks of gestation due to fetal heart failure and hydrops. The other 36 cases underwent surgical resection of tumor within 3 weeks after birth with good prognosis. (2) TFR>0.12 before 28 weeks of gestation could predict poor fetal prognosis, with a sensitivity of 100.0%, a specificity of 86.1% and an area under curve (AUC) of 0.922 (P<0.01). Among the fetuses with TFR>0.12, 5/10 had poor prognosis, while the fetuses with TFR≤0.12 all had good prognosis (100%,31/31), and the difference between the two groups was statistically significant (P<0.001). (3) TGR>48 cm3/week could predict poor fetal prognosis with a sensitivity of 100.0%, a specificity of 78.3% and an AUC of 0.880 (P<0.05). (4) Among the 28 SCT fetuses delivered in our hospital, the incidence rate of poor fetal prognosis was 0 (0/20) in those with solid tumor component<50%, and 5/8 in those with solid tumor component ≥50%, and the difference between the two groups was statistically significant (P<0.01). The incidence rate of poor fetal prognosis was 2/2 in those with placentomegaly (all with fetal hydrops), and 12% (3/26) in those without placentomegaly. The risk of poor fetal prognosis was 8.67 times higher in those with placentomegaly than those without placentomegaly, and the difference between the two groups was statistically significant (P<0.05). The incidence rate of poor fetal prognosis in those with polyhydramnios was 3/7, and 10% (2/21) in those without polyhydramnios, but there was no statistically significant difference between the two groups (P>0.05). Conclusion: TFR combined with solid tumor morphology, TGR, and presence of placentomegaly could predict the adverse pregnancy outcomes of fetal SCT.

[Preliminary clinical experience of the novel transcatheter aortic valve system Prizvalve® for the treatment of severe aortic stenosis].

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.

[Analysis of molecular and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the intensive care unit].

To investigate the carbapenemases distribution of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the intensive care unit, and the clinical characteristics between carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) and carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP) were compared. A total of 53 non-repetitive CRKP strains isolated from 49 patients in the intensive care unit of the Second Affiliated Hospital of Xi'an Jiaotong University from May 2020 to March 2021 were retrospectively studied. The carbapenemase inhibitor enhancement test was used for screening carbapenemase-producing strains, and the string test was carried out to screen the hypermucoviscosity phenotype. Using PCR to detect five main carbapenemase genes (blaKPC-2, blaNDM, blaIMP , blaVIM and blaOXA-48-like), common serotype (K1 and K2) and virulence gene (rmpA and iutA). Treated the strains with both rmpA and iutA genes as hypervirulent Klebsiella pneumonia (hvKP), and the whole genome sequencing of CR-hvKP was completed. At the same time, the clinical data of 49 patients were sorted out, and the differences in clinical characteristics of CR-hvKP and CR-non-hvKP infected patients were compared using the independent sample t test, Mann-Whitney U test, chi-square test or Fisher's exact probability test. CRKP isolated from the intensive care unit were extensively drug resistance and still had a good sensitivity to polymyxin B and tigecycline. Producing carbapenemases were the main resistance mechanism of CRKP (52/53, 98.1%). Of the 53 CRKP strains, except for 1strain that did not detect carbapenemase, at least one carbapenemase resistance gene was detected in the remaining 52 CRKP strains, of which 45 strains carried an enzyme, including 36 blaKPC-2 (36/53, 67.9%), 8 blaNDM (8/53, 15.1%), 1 blaIMP (1/53, 1.9%), and 7 strains carried with both blaKPC-2 and blaNDM (7/53, 13.2%). String test and virulence gene showed that 7 CR-hvKP strains (13.2%) were detected in 53 CRKP strains, and two of which were hypermucoviscosity phenotype. Sequencing results revealed that CR-hvKP were mainly ST11 type. Almost all patients with CR-hvKP infection were over 60 years old (7/7), with invasive treatment (7/7), pulmonary infection with hypermucoviscosity phenotype (2/7) and high mortality (5/7); and the percentage of neutrophils in patients with CR-hvKP infection (86.44±4.70) % was higher than those patients with CR-non-hvKP infection (78.90±19.15) %, the difference was statistically significant (t=-2.225, P=0.032). The CR-hvKP strains in the intensive care unit mainly produced KPC-2 enzyme, with K2 capsular serotype and ST11 type. It is necessary to strengthen the monitoring and control of the CR-hvKP strain to prevent the co-evolution of drug-resistant and hypervirulent strains.

[Clinical features and perinatal outcomes of 48 cases of pregnancy complicated with placental cystic lesions].

Objective: To investigate the clinical characteristics and perinatal outcomes of pregnancy with placental cystic lesions. Methods: A retrospective study was carried out on 48 pregnant women diagnosed as pregnancy complicated with placental cystic lesions from January 2000 to January 2020 at the Women's Hospital, Zhejiang University School of Medicine. The clinical features, pathological diagnosis and perinatal outcome were analyzed. Results: The age of 48 cases was (30±5) years, and the diagnostic gestational week of ultrasound was (24±8) weeks. Twenty-five cases in which showed a cystic mass at the fetal surface were diagnosed as placental cyst. The live birth rate was 100% (25/25) and the premature birth rate was 20% (5/25). Twenty-three cases showed "honeycomb like" cystic echo. Cystic lesions of 10 cases were located in the uterine cavity connected with the margin of the normal placenta, and finally diagnosed as hydatidiform mole and coexisting fetus (HMCF). Six cases of HMCF terminated pregnancy, and the live birth rate was 4/10, the premature delivery rate was 2/4. Cystic lesions of 13 cases were located in the placenta substance, and finally diagnosed as 4 cases of placental mesenchymal dysplasia (PMD) and 9 cases of focal chorionic edema; the live birth rate was 6/13 and the premature delivery rate was 4/6. The median hCG was lower in focal chorionic edema group [80 kU/L (60-110 kU/L)] than in the groups of HMCF [240 kU/L (180-430 kU/L)] and PMD [360 kU/L (210-700 kU/L)], and the differences were statistically significant (all P<0.01). Conclusions: For pregnancy complicated with placental cystic lesions, prenatal ultrasound should be performed to evaluate the shape, location and blood flow of the lesions. Maternal serological examination and invasive prenatal diagnosis are helpful for prenatal diagnosis and treatment. Due to the difference of perinatal outcomes, maternal and fetal complications, individualized pregnancy management should be carried out.

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice.

BACKGROUND: Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. RESULTS: A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. CONCLUSIONS: These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

[Clinical and genetic characteristics of patients with chronic enteropathy associated with SLCO2A1 gene].

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.

[Clinical characteristics and microbiome analysis in patients with anti-programmed cell death protein 1 related colitis].

Objective: To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis. Methods: Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse. Results: The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutes decreased with Bacteroidetes increasing in phylum level; while the Bacteroides increased with Ruminococcaceae decreasing in genus level. Lactobacillus was the potentially beneficial genus. Conclusion: Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

[Different viral doses of cytomegalovirus infection in the left and right colons].

Objective: To compare the differences in the detection rates of cytomegalovirus (CMV) infection between the left and right colons for guiding endoscopic biopsy-sites. Methods: The cases of colonic CMV infection confirmed by histology at the Peking Union Medical College Hospital from July 2015 to July 2018 were collected and analyzed. Splenic curvature was used as the dividing point between the left and right colons. The CMV inclusions were identified histologically, and the CMV infected cells were detected using immunohistochemistry (EnVision method). The numbers of infected cells in the left and right colons were compared by histological and immunohistochemical results. A total of 731 patients were identified. Ten of the 731 patients had histological specimens of both left and right colons and were confirmed with CMV EnVision immunohistochemical study. There were 25 biopsy or resection specimens. Seven patients were male and 3 were female, and their ages ranged from 29 to 66 years, with a median age of 55 years. All of the 10 patients were also diagnosed with ulcerative colitis. Results: The number of the cells infected with CMV in the left colon was 115 (1-41), while that in the right colon was 76 (0-51). In 8/10 cases, the number of CMV infected cells in the left colon was more than that in the right colon. Conclusions: The study on the biopsies and resection specimens suggests that CMV infection is mostly present in the left colon. The left colon thus might be an important endoscopic biopsy-site for the cases with suspicion of CMV infection.

[Endoscopic features and clinical correlation analysis of 24 patients with Cronkhite-Canada syndrome].

Objective: To clarify the endoscopic changes prior to corticosteroid therapy in Cronkhite-Canada syndrome (CCS) patients and to explore the correlation between endoscopic features and clinical characteristics. Methods: A total of 24 CCS patients who were hospitalized in Peking Union Medical College Hospital from January 1999 to June 2019 and underwent gastroscopy and colonoscopy before corticosteroid therapy were retrospectively enrolled. The endoscopic images were re-interpreted. The demographic characteristics, clinical manifestations, laboratory tests and histopathological data were collected and analyzed. Results: Of all 24 patients, 15 (62.5%) were male and 9(37.5%) were female, with an average age of (59±10) years and disease course of 6 (1~36) months. Based on the endoscopic findings, the percentages of stomach, colon, duodenum, rectum and terminal ileum involvement were 100%, 100%, 95.7%, 66.7% and 50.0% respectively. Gastric involvement was more severe in the lower part of the body and the antrum of the stomach, while the cardia and the fundus were spared in 5 (20.8%) cases. Colonic involvement was more severe in the right colon. No patient showed remarkable esophageal involvement. The typical appearance under endoscopy were diffuse mucosal hyperemia and edema with polyps or nodular changes. The lesions may have mulberry-like or imbricate changes in severe cases. Lymphatic dilation in the duodenum was found in 47.8% patients. Most of the polyps were pedunculated or sub-pedunculated, with occasionally seen sessile polyps in the colon. The pit patterns of the 12 resected colon polyps in 11 patients could be classified as Kudo type Ⅲ(S), Ⅲ(L), Ⅳ and Ⅴ(I), among which 2 tubular adenomas had the Kudo type Ⅲ(L). Other resected polyps were hyperplastic polyps or CCS polyps. The disease duration prior to diagnosis was positively correlated with the maximum diameter of colon polyps (r=0.625, P=0.006). Serum albumin levels in patients with whole stomach involvement were significantly lower than those in patients with cardia spared [(29±8) g/L vs (37±5) g/L, P=0.034]. Conclusions: The typical initial endoscopic finding of CCS is multiple polyps or nodular changes on the background of diffuse hyperemia and edema lining the gastric, duodenal and colonic mucosa. Lymphatic dilatation in the duodenum could also be found. Some endoscopic features are correlated to clinical characteristics.

[Analysis of influencing factors of endometrial disease of patients with breast cancer after operation].

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

[The 471st case: duodenal ulcer, mucor infection, and elevated IgG(4)].

Mucor infection is rarely reported in non-immunocompromised population, especially in isolated gastrointestinal tracts. IgG(4)-related diseases (IgG(4)-RD) have been recognized in recent years, but secondary causes of IgG(4) elevation should be differentiated. We reported a young man with duodenal mass and ulcer and high serum IgG(4) level. Histological biopsy of the mass revealed positive mucor mycelium and infiltration of IgG(4) positive plasma cells. Serum IgG(4) decreased to normal range after surgical resection and systemic antifungal treatment. This case suggests that isolated mucor mycosis infection can develop in the digestive tract and mimics as IgG(4)-related disease.

Oxygen Electromigration and Energy Band Reconstruction Induced by Electrolyte Field Effect at Oxide Interfaces.

Electrolyte gating is a powerful means for tuning the carrier density and exploring the resultant modulation of novel properties on solid surfaces. However, the mechanism, especially its effect on the oxygen migration and electrostatic charging at the oxide heterostructures, is still unclear. Here we explore the electrolyte gating on oxygen-deficient interfaces between SrTiO_{3} (STO) crystals and LaAlO_{3} (LAO) overlayer through the measurements of electrical transport, x-ray absorption spectroscopy, and photoluminescence spectra. We found that oxygen vacancies (O_{vac}) were filled selectively and irreversibly after gating due to oxygen electromigration at the amorphous LAO/STO interface, resulting in a reconstruction of its interfacial band structure. Because of the filling of O_{vac}, the amorphous interface also showed an enhanced electron mobility and quantum oscillation of the conductance. Further, the filling effect could be controlled by the degree of the crystallinity of the LAO overlayer by varying the growth temperatures. Our results reveal the different effects induced by electrolyte gating, providing further clues to understand the mechanism of electrolyte gating on buried interfaces and also opening a new avenue for constructing high-mobility oxide interfaces.