Immunotherapy had completely changed the treatment for patients with advanced non-small cell lung cancer.However,due to its low response rate as a monotherapy,many patients had not been able to benefit from the treatment.The combination of immunotherapy with anti-angiogenic drugs and chemotherapy might have helped to address this issue,and the regimen of atezolizumab with bevacizumab,carboplatin,and paclitaxel(ABCP)had been approved as a first-line treatment for advanced metastatic non-small cell lung cancer,holding great potential for application.This review had summarized the antitumor mechanisms of the ABCP regimen,had concluded the current status of its clinical application for different subgroups and treatment sequences,the safety and cost-effectiveness of the regimen,as well as the possibilities for alternative drug choices within the ABCP regimen and the development of new drugs,providing a reference for the personalized application of the ABCP regimen in patients with non-small cell lung cancer.

Objective: To investigate the safety and feasibility of performing right colectomy via a transvaginal approach. Methods: This was a retrospeltive cohort study. Data of 30 patients who had undergone transvaginal laparoscopic right colectomy (transvaginal group) and 23 women who had undergone laparoscopic right colectomy (laparoscopic group) from January 2019 to March 2022 in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital were collected retrospectively. The inclusion criteria for the transvaginal group were as follows: (1) post-menopausal woman; (2) transverse diameter of the tumor < 6 cm; and (3) diagnosis of benign polyps that were unresectable by endoscopy, mucinous tumors of the appendix, or confirmed right colon cancer not requiring D3 lymphadenectomy. The inclusion criteria for the laparoscopic group were as follows: (1) pathologically confirmed adenocarcinoma or high-grade intraepithelial neoplasia; (2) lesion located from the cecum to the right third of the transverse colon; and (3) clinically stage T1-4NanyM0. The exclusion criteria for the laparoscopic group were as follows: (1) distant metastasis discovered during surgical exploration; (2) multiple organ resection required or R0 resection not possible; or (3) conversion to open surgery required. Safety was evaluated on the basis of intra- and post-operative complications. Feasibility was assessed by postoperative recovery and quality of operative specimen. The body mass index was lower in the transvaginal than the laparoscopic group (22.0±3.1 kg/m² vs. 24.1±2.6 kg/m², t=2.617, P=0.012). Results: Among the 30 transvaginal laparoscopic right colectomies, 26 were pure transvaginal surgeries, three required laparoscopic assistance because of difficulties with anastomosis (n=2) or abdominal adhesions (n=1), and one required conversion to laparoscopic surgery because of vascular injury. Compared with the laparoscopic group, the transvaginal group had a longer surgery time (175.0 [147.5, 216.3] minutes vs. 120.0 [100.0, 120.0] minutes, U=63.000, P<0.001) and more blood loss (30.0 [10.0, 50.0] ml vs. 23.0 [10.0, 20.0] ml, U=208.000, P=0.011). The incidence of intraoperative complications (16.7% [5/30) vs. 0, P=0.061] was comparable between the two groups. In the transvaginal group, the sites of intraoperative injuries were bladder (n=3), ileocecal artery (n=1), and right uterine artery (n=1). The incidence of postoperative complications (20.0% [6/30] vs. 17.4% [4/23], χ²<0.001,P>0.999) was also comparable between the two groups. Clavien-Dindo grade III postoperative complications occurred in two patients in the transvaginal group (one patient had a pelvic hematoma that required embolization; the other had a vesico-vaginal fistula that required surgery). Postoperative visual analogue scale scores were significantly lower (P<0.001) in the transvaginal group. Times to first flatus, ambulation, and first intake and duration of postoperative hospital stay were comparable between the two groups (P>0.05). The proportion of specimens of moderate quality was 83.3% (25/30) in the transvaginal group and 100% (23/23) in the laparoscopic group; this difference is not significant (P=0.061). Among patients who underwent D2 lymph node dissection, the number of lymph nodes examined was comparable between the transvaginal (n=23) and laparoscopic groups (n=7) (18 [15, 27] vs. 20 [16, 29], U=69.500, P=0.589). Conclusion: Transvaginal right colon surgery is associated with less postoperative pain than laparoscopic surgery, but is not yet the preferred alternative because of the incidence of surgical complications.
Humans ; Female ; Retrospective Studies ; Cohort Studies ; Feasibility Studies ; Treatment Outcome ; Postoperative Complications/epidemiology* ; Laparoscopy ; Colectomy

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.
Humans ; Male ; Adolescent ; Adult ; Female ; Protein Kinase Inhibitors/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Treatment Outcome ; Retrospective Studies ; Dasatinib/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Thrombocytopenia

ObjectiveCentral nervous system （CNS） infiltration commonly occurs in children with acute lymphoblastic leukemia （ALL）. Early subclinical CNS infiltration in pediatric ALL is hard to detect with conventional methods. This study aimed to investigate the changes of brain structure volume parameters based on Synthetic MRI （SyMRI） in pediatric ALL without clinically diagnosed CNS infiltration. MethodsThirty-six ALL and twenty-nine typically developing （TD） children were prospectively collected and all underwent SyMRI. The Synthetic MR software was used to obtain brain volumetric parameters including total white matter volume （WMV）， gray matter volume （GMV）， cerebrospinal fluid （CSF） volume， etc. and their within-group differences were assessed by analysis of covariance. The Spearman correlation analysis was used to examine the correlation between biological characteristics and statistically significant brain volume parameters. ResultsALL children showed increased CSF volume （P_{FDR-corrected} = 0.009） and decreased GMV （P_{FDR-corrected} = 0.027） when compared to TD children. We also found a moderately negative association between GMV/intracranial volume and risk classification in pediatric ALL （rs = -0.380， P = 0.022）. ConclusionsPediatric ALL without clinically diagnosed CNS infiltration presented with accumulation of CSF and reduction of gray matter. The brain volumetric changes in subclinical CNS infiltration of pediatric ALL provides a new attempt for exploring the underlying mechanism and early detection of CNS infiltration in pediatric ALL.

ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （P_{FDR-corrected} = 0.048） and increased Dzassoc value （P_{FDR-corrected} = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （P_{FDR-corrected} < 0.001）. ALPS-index was negatively associated with the risk classification （r_s = -0.47， P = 0.018） as well as immunophenotype （r_s = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.

Objective: To explore the incidence and risk factors of postoperative surgical site infection (SSI) after colon cancer surgery. Methods: A retrospective case-control study was performed. Patients diagnosed with colon cancer who underwent radical surgery between January 2016 and May 2021 were included, and demographic characteristics, comorbidities, laboratory tests, surgical data and postoperative complications were extracted from the specialized prospective database at Department of General Surgery, Peking Union Medical College Hospital. Case exclusion criteria: (1) simultaneously multiple primary colon cancer; (2) segmental resection, subtotal colectomy, or total colectomy; (3) patients undergoing colostomy/ileostomy during the operation or in the state of colostomy/ileostomy before the operation; (4) patients receiving natural orifice specimen extraction surgery or transvaginal colon surgery; (5) patients with the history of colectomy; (6) emergency operation due to intestinal obstruction, perforation and acute bleeding; (7) intestinal diversion operation; (8) benign lesions confirmed by postoperative pathology; (9) patients not following the colorectal clinical pathway of our department for intestinal preparation and antibiotic application. Univariate analysis and multivariate analysis were used to determine the risk factors of SSI after colon cancer surgery. Results: A total of 1291 patients were enrolled in the study. 94.3% (1217/1291) of cases received laparoscopic surgery. The incidence of overall SSI was 5.3% (69/1291). According to tumor location, the incidence of SSI in the right colon, transverse colon, left colon and sigmoid colon was 8.6% (40/465), 5.2% (11/213), 7.1% (7/98) and 2.1% (11/515) respectively. According to resection range, the incidence of SSI after right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy was 8.2% (48/588), 4.5% (2/44), 4.8% (8 /167) and 2.2% (11/492) respectively. Univariate analysis showed that preoperative BUN≥7.14 mmol/L, tumor site, resection range, intestinal anastomotic approach, postoperative diarrhea, anastomotic leakage, postoperative pneumonia, and anastomotic technique were related to SSI (all P<0.05). Multivariate analysis revealed that anastomotic leakage (OR=22.074, 95%CI: 6.172-78.953, P<0.001), pneumonia (OR=4.100, 95%CI: 1.546-10.869, P=0.005), intracorporeal anastomosis (OR=5.288, 95%CI: 2.919-9.577,P<0.001) were independent risk factors of SSI. Subgroup analysis showed that in right hemicolectomy, the incidence of SSI in intracorporeal anastomosis was 19.8% (32/162), which was significantly higher than that in extracorporeal anastomosis (3.8%, 16/426, χ(2)=40.064, P<0.001). In transverse colectomy [5.0% (2/40) vs. 0, χ(2)=0.210, P=1.000], left hemicolectomy [5.4% (8/148) vs. 0, χ(2)=1.079, P=0.599] and sigmoid colectomy [2.1% (10/482) vs. 10.0% (1/10), χ(2)=2.815, P=0.204], no significant differences of SSI incidence were found between intracorporeal anastomosis and extracorporeal anastomosis (all P>0.05). Conclusions: The incidence of SSI increases with the resection range from sigmoid colectomy to right hemicolectomy. Intracorporeal anastomosis and postoperative anastomotic leakage are independent risk factors of SSI. Attentions should be paid to the possibility of postoperative pneumonia and actively effective treatment measures should be carried out.
Case-Control Studies ; Colonic Neoplasms/surgery* ; Humans ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection/etiology*

Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan（DSS） on angiotensin Ⅱ （AngⅡ）/transient receptor potential cation channel 6 （TRPC6） pathway in nephrotic syndrome （NS） rats. Method:In animal experiments， doxorubicin （4 mg·kg^-1 for the 1^st week and 2 mg·kg^-1 for the 2^nd week） was injected twice to the tail vein of rats to induce NS model in 160 rats， which were then randomly divided into model group （normal saline）， losartan group （30 mg·kg^-1·d^-1）， and low-（4.3 g·kg^-1·d^-1）， medium-（8.6 g·kg^-1·d^-1）， and high-dose （17.2 g·kg^-1·d^-1） DSS groups. Besides， a normal group was also set. After intervention for four weeks， ultrastructure changes of the kidney were identified by transmission electron microscopy （TEM）. The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin （CaN） in plasma. Western blot was used to detect the protein expression of TRPC6， angiotensin Ⅱ type 1 receptor （AT1R）， podocyte slit diaphragm-specific protein （Nephrin）， and cysteine-aspartic acid protease-3 （Caspase-3） in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments， AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group， an AngⅡ group， an AngⅡ+SAR7334 （TRPC6-specific inhibitor） group， an AngⅡ+5%DSS group， an AngⅡ+10%DSS group， and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6， AT1R， Nephrin， and Caspase-3 in podocytes. Result:Compared with the normal group， the model group showed increased 24-hour urine protein content （P<0.01） and AngⅡ and CaN in plasma （P<0.01）， incomplete glomerular structure， the extensive fusion of podocyte process with elevated fusion rate （P<0.01）， increased expression distribution of AT1R and TRPC6 in the renal cortex， and up-regulated protein expression of AT1R， TRPC6， and Caspase-3 in renal tissues （P<0.01）， and reduced Nephrin protein expression （P<0.01）. Compared with model group， the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content （P<0.01） and the content of AngⅡ and CaN in plasma （P<0.01）， improved glomerular structure， reduced fusion rate of podocyte process （P<0.01）， diminished expression distribution of TRPC6 and AT1R in the renal cortex， declining protein expression of AT1R， TRPC6 and Caspase-3 in renal tissues （P<0.01）， and elevated Nephrin protein expression （P<0.01）. Additionally， compared with the normal podocytes， AngⅡ-stimulated podocytes showed increased protein expression of AT1R， TRPC6 and Caspase-3 （P<0.01）， and decreased expression of Nephrin （P<0.01）. Compared with the AngⅡ group， the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R， TRPC6， and Caspase-3 （P<0.01） and increased protein expression of Nephrin （P<0.01）. Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.
Dasatinib/therapeutic use* ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Pyrimidines/therapeutic use* ; Retrospective Studies ; Treatment Outcome

A 51-year-old woman presented with metachronous tumor development in bilateral breasts, thyroid, and endometrium. Additional signs and symptoms fulfilled the National Comprehensive Cancer Network criteria for Cowden syndrome. Immunohistochemistry showed loss of PTEN expression in all tumors. Single nucleotide variants, 647 germline variants (including one each in PTEN and MSH3), and 21 somatic mutations within exons were detected in all tumors after whole-exome sequencing. There were 0, 11, and 46 specific somatic mutations in bilateral breasts, thyroid, and endometrial cancers, respectively.Although PTEN mutation is key to the development of Cowden syndrome, DNA repair dysfunction might be the initial driver of mutations. Fewer mutations were required to induce initial bilateral breast carcinomas, with subsequent thyroid and endometrial carcinomas requiring more mutations for induction. When genetic screening is unavailable, breast cancer patients with clinical manifestations of Cowden syndrome must be carefully assessed for secondary malignancies, such as thyroid and endometrial carcinomas.