New Limits on Exotic Spin-Dependent Interactions at Astronomical Distances.

Exotic spin-dependent interactions involving new light particles address key questions in modern physics. Interactions between polarized neutrons (n) and unpolarized nucleons (N) occur in three forms: g_{S}^{N}g_{P}^{n}σ·r, g_{V}^{N}g_{A}^{n}σ·v, and g_{A}^{N}g_{A}^{n}σ·v×r, where σ is the spin and g's are the corresponding coupling constants for scalar, pseudoscalar, vector, and axial-vector vertexes. If such interactions exist, the Sun and Moon could induce sidereal variations of effective fields in laboratories. By analyzing existing data from laboratory measurements on Lorentz and CPT violation, we derive new experimental upper limits on these exotic spin-dependent interactions at astronomical ranges. Our limits on g_{S}^{N}g_{P}^{n} surpass the previous combined astrophysical-laboratory limits, setting the most stringent experimental constraints to date. We also report new constraints on vector-axial-vector and axial-axial-vector interactions at astronomical scales, with vector-axial-vector limits improved by ∼12 orders of magnitude. We extend our analysis to Hari Dass interactions and obtain new constraints.

[Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai].

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 µg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 µg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

[Reproducibility evaluation of air-charged catheter for rest urethral pressure profilometry].

We retrospectively included 53 (9 males, 44 females) patients who underwent rest urethral pressure profilometry (RUPP) due to lower urinary tract symptoms (LUTS) in Beijing Chaoyang Hospital from May 2021 to March 2022. The age of patients was (55±16) (25-76) years old. The clinical diagnoses of the included patients with lower urinary tract symptoms were classified as: benign prostatic hyperplasia in 9 cases, interstitial cystitis in 1 case, stress urinary incontinence in 11 cases and non-obstructive dysuria in 32 cases. The full set of urodynamic examination was composed of bladder pressure measurement during the filling period, pressure flow study (PFS) and RUPP. All the urodynamic examination was performed by air-charged catheter (ACC) and corresponding equipment. All patients underwent RUPP measurements twice. The vesical pressure (Pves) values were (35.30±6.15), (35.81±5.91) cmH2O (1 cmH2O=0.098 kPa); the Pura@max were (141.91±36.53), (145.02±38.85) cmH2O; functional urethral length were (41.70±16.34), (42.55±16.40) mm; the maximum urethral closure pressure for the two RUPP measurements were (106.57±36.44), (109.41±39.27) cmH2O. There was no statistical difference between the two RUPP measurements (P>0.05). The reproducibility of the RUPP measurements obtained by ACC is good and deserves further study.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.

[Diagnostic value of urethral pressure profile for female bladder neck obstruction using air-charged catheters].

Objective: To evaluate the measurements of urethral pressure profile (UPP) using air-charged catheters (ACC) in women with bladder neck obstruction and to preliminarily analyze the diagnostic value of UPP based on ACC for female bladder neck obstruction. Methods: Retrospective inclusion of 63 female patients with bladder neck obstruction diagnosed in the Department of Urology of Beijing Chao-yang Hospital from September 2020 to December 2021 were included as the observation group, and 45 female patients who came to the hospital due to lower urinary tract symptoms with non-bladder neck obstruction during the same period were selected as the control group. All patients received urodynamic examination and UPP examination based on ACC, and urethral pressure measurements [M (Q1, Q3)] were compared between the two groups and analyzed the predictive value of the relevant measurements for female bladder neck obstruction. Results: The age of the observation group was 61 (47, 67) years and body mass index (BMI) was 24.1 (21.6, 27.9) kg/m2, the age of the control group was 65 (58, 71) years and BMI was 25.0 (22.8, 27.6) kg/m2. The urethral pressure at the bladder neck and urinary sphincter position in the observation group were higher than control group[104.00 (83.00, 124.00) cmH2O (1 cmH2O=0.098 kPa) vs 42.00 (31.00, 65.50) cmH2O, 125.0 (107.0, 154.0) cmH2O vs 99.0 (77.0, 124.0) cmH2O, P<0.001]. The results of the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of urethral pressure at the bladder neck position had the highest predictive value for female bladder neck obstruction (AUC: 0.946, 95%CI: 0.886-0.981, sensitivity: 87.3%, specificity: 91.1%), and the results of interaction point plot showed that the cut-off value was 72 cmH2O. The cut-off value of urethral pressure at the bladder neck position was used as positive cut-off value to predict female patients with bladder neck obstruction. Sixty-three patients with bladder neck obstruction were detected by UPP measurement using ACC in 59 cases (59/63, 93.7%) and the Kappa value was 0.774 (95%CI: 0.654-0.894), indicating that UPP had high consistency with pressure-flow study. Conclusions: UPP examination based on ACC can show the pressure values of the bladder neck and urethral sphincter position. When the urethral pressure of the bladder neck position is greater than 72 cmH2O, it is helpful for the diagnosis of female bladder neck obstruction and has guiding significance for the diagnosis and treatment of this disease.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

[Efficacy analysis of selective genicular artery embolization in the treatment of knee pain secondary to osteoarthritis].

Objective: To evaluate the efficacy and safety of selective genicular artery embolization for the treatment of the knee pain secondary to osteoarthritis. Methods: From October 2020 to July 2021, 17 patients (23 knees) aged (68±7) years with moderate to severe knee pain secondary to knee osteoarthritis were prospectively included in the General Hospital of Ningxia Medical University. There were 6 males and 11 females included in this research. Patients were assessed with knee pain, stiffness, and function with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, using the Kellgren-Lawrence (K-L) grading to evaluate the severity of KOA, and using the Magnetic Resonance Knee Osteoarthritis Score (MOAKS) to evaluate the MR imaging characteristics of the affected knee. Selective genicular artery embolization (GAE) was performed in all patients. The patients were followed up for 6 months after the procedure. Patients were assessed with the VAS score and WOMAC scale at 1 d, 1 week and 1, 3 and 6 months after the procedure to evaluate the clinical outcomes, including the improvement of knee joint pain, stiffness and function, as well as the occurrence of adverse reactions. Results: Three to seven genicular artery branches were superselected and embolized in 23 knees, and 4 to 7 genicular artery branches were embolized in 7 patients with K-L grade 4. The clinical improvement was 95.6% (22/23) at 1 month, 86.9% (20/23) at 3 months, and 91.3% (21/23) at 6 months. Twenty-three knees completed the 6-month follow-up, and the VAS score, WOMAC pain score, and total WOMAC score at 1, 3, and 6 months after surgery were (2.5±1.3), (3.4±2.4), and (19.7±9.8) points, (3.0±1.8), (4.5±3.4), and (22.3±11.3) points, (2.8±1.5), (4.1±3.0), and (20.5±11.0) points, which were lower than the (6.6±0.9), (11.4±2.6) and (47.0±12.0) points at baseline (all P<0.001). During the follow-up period, 7 patients had adverse reactions: 3 cases had skin ecchymosis in the femoral artery puncture area, 4 cases had knee joint stiffness and pain within 1 day after operation, which were relieved spontaneously in 1 week, 6 patients had joint clicking during extension and flexion activities after operation, of which 3 cases subsided spontaneously within 3 months after operation. None of the patients had major procedure-related adverse events. Conclusion: GAE has a high clinical improvement rate and a low incidence of adverse reactions in the treatment of the pain secondary to knee osteoarthritis, which provides a new treatment option for patients who fail to respond to conservative treatment.

[Study on the etiological characteristics and prevention and control of adult community-acquired pneumonia in hospitalized patients in a hospital in Beijing from 2015 to 2019].

Objective: To explore the distribution characteristics of pathogens in adult patients with community-acquired pneumonia (CAP) and to provide basis for the diagnosis, treatment, prevention of CAP. Methods: 1 446 inpatients with CAP were prospectively enrolled in a third-class hospital in Beijing in recent 5 years (from January 2015 to December 2019). Respiratory tract samples were collected for smear, culture, nucleic acid, antigen and antibody detection to identify the pathogen of CAP. Mann-Whitney U test was used for continuous variables and χ2 test or Fisher's exact test was used for categorical data for statistical analysis. Results: Among the 1 446 patients, 822 (56.85%) patients were infected with a single pathogen, 231 (15.98%) patients were infected with multiple pathogens, and 393 (27.18%) patients were not clear about the pathogen. Influenza virus is the first pathogen of CAP (20.95%, 303/1 446), mainly H1N1 (8.51%, 123/1 446), followed by mycoplasma pneumoniae (7.19%, 104/1 446), Mycobacterium tuberculosis (5.33%, 77/1 446) and Streptococcus pneumoniae (5.05%, 73/1 446). The outbreak of H1N1 occurred from December 2018 to February 2019, and the epidemic of mycoplasma pneumoniae pneumonia was monitored from August to November 2019. Patients under 65 years old had high detection rates of Mycoplasma pneumoniae (14.41% vs. 2.41%, χ²=74.712,P<0.001), Streptococcus pneumoniae (8.16% vs. 2.99%, χ²=18.156, P<0.001), rhinovirus (6.08% vs. 3.56%, χ²=5.025, P<0.025), Chlamydia pneumoniae (5.90% vs. 1.15%, χ²=26.542, P<0.001) and adenovirus (3.13% vs. 0.92%, χ²=9.547, P=0.002). The severe disease rate of CAP was 14.66% (212/1 446), and the average mortality rate was 3.66% (53/1 446). The severe illness rate and mortality rate of bacterial-viral co-infection were 28.97% (31/107) and 19.63% (21/107), respectively. Conclusions: Influenza virus is the primary pathogen of adult CAP. Outbreaks of Mycoplasma pneumoniae and H1N1 were detected in 2018 and 2019, respectively. The remission rate and mortality rate of virus-bacteria co-infection were significantly higher than those of single pathogen infection. Accurate etiological basis not only plays a role in clinical diagnosis and treatment, but also provides important data support for prevention and early warning.

[Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology].

Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

[Analysis of PARP inhibitors induced anemia in advanced and relapsed epithelial ovarian cancer].

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

[Clinicopathological and survival analysis of 34 cases of uterine clear cell carcinoma].

Objective: To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC). Methods: UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS (P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS (P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients (P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage (P=0.009). Conclusions: The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

[Clinical characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease].

Objective: To study the clinical and etiological characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease(VP-COPD), and to identify the risk factors associated with poor prognosis. Methods: From August 1, 2017 to August 1, 2019, totally 235 patients in a general hospital in Beijing were prospectively enrolled in this research, and all patients were diagnosed with viral pneumonia by imaging and etiology. The patients were divided into VP-COPD group(n=60) and VP-nCOPD(viral pneumonia in non-COPD patients) group(n=175). Pathogen detection and clinical characteristics were compared between the two groups.Finally, the binomial logistic regression was used to explore the risk factors associated with severe VP-COPD. Results: Compared with the VP-nCOPD group, the VP-COPD group was older(76.5 vs 66.0 years, P=0.001), and the CURB-65 score(2 vs 1, P= 0.001) and the PSI score(111 vs 85, P<0.001) were higher at admission. Pseudomonas aeruginosa(χ²= 10.308, P= 0.001) and Staphylococcus aureus(χ²= 5.953, P=0.028) were the most common co-infection bacteria. In the VP-COPD group type Ⅱ respiratory failure was more common(23.3% vs 6.8%, P<0.001), the number of severely ill patients was larger(48.3% vs 30.3%, P=0.011), the length of hospital stay was longer(13 vs 8, P<0.001), and the mortality rate during hospitalization was higher(18.3% vs 7.4%, P=0.016) in the VP-nCOPD group. Multivariate analysis showed that the level of blood glucose(OR: 1.73, 95%CI: 1.22-2.44, P= 0.002) and pleural effusion(OR: 133.12, 95%CI: 7.57-2 340.36, P=0.001) were risk factors for severe VP-COPD patients. Conclusion: Viral pneumonia in patients with COPD tended to develop into severe cases and had a poor prognosis.

[Clinicopathological characteristics and outcomes of 122 patients with colorectal cancer metastasize to the ovary].

Objective: To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer. Methods: A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis. Results: The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy (P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion: Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

[Diagnosis, treatment and prognosis of uterine serous carcinoma].

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.

The neutrophil to lymphocyte ratio as a novel predictor of asthma and its exacerbation: a systematic review and meta-analysis.

OBJECTIVE: It is widely known that the main white blood cell populations, and neutrophil to lymphocyte ratio (NLR), are involved in systemic inflammation. The usefulness of NLR measurements has been reported in patients with asthma. We performed a systematic review and meta-analysis of studies to investigate the relationship between the NLR and asthma and its exacerbations. MATERIALS AND METHODS: We systematically searched PubMed and Embase databases for studies (published between Jan 1, 1950 and Jan 2, 2020; no language restrictions) comparing the NLR values in patients with stable asthma or asthma exacerbations to healthy controls. We assessed pooled data by use of a random-effects model. RESULTS: Of 260 identified studies, 6 were eligible and were included in our analysis (N = 2418 participants). Compared with 439 healthy controls, 743 stable asthma patients in four studies showed significantly greater NLR values (standardized mean difference, SMD, 0.567, 95% CI 0.212-0.922; p = 0.002). Furthermore, compared with 1063 stable asthma patients, 402 asthma exacerbation patients yielded significantly greater NLR values (random effects SMD 1.335, 95% CI 0.429-2.241; p < 0.001). CONCLUSIONS: Our meta-analysis showed that the NLR values are a reasonable and easy-to-use marker for asthma and its exacerbations. Further studies, with larger sample sizes and more phenotypes, are required to establish its use as a predictive parameter in asthma.

[The preliminary clinical study on radical prostatectomy without preoperative prostate biopsy].

Objective: To investigate the feasibility and safety of minimally invasive radical prostatectomy for prostate cancer patients without preoperative prostate biopsy in the new era of the continuous development of comprehensive new imaging diagnostic mode and minimally invasive surgery technology. Methods: From August 2018 to October 2019, 17 patients with prostate cancer were enrolled in this study in the Cancer Hospital, Chinese Academy of Medical Sciences. All patients were highly suspected of prostate cancer by PSMA-PET/CT-based imaging diagnostic techniques and underwent 3D laparoscopic radical prostatectomy without prostate biopsy. The perioperative data, postoperative pathology, postoperative complications and follow-up results were recorded and analyzed. Results: The average age of 17 patients with prostate cancer was (65±7) years. The body mass index (BMI) average was (24.4±3.0) kg/m(2). The American Society of Anesthesiologists (ASA) score was 1 (1-2) and the Charlson comorbidity index (CCI) score was 1 (0-4). The preoperative value of PSA was (19±11) µg/L. The PSMA PET/CT showed abnormally high expression foci and the great possibility of prostate cancer for all the 17 patients. Prostate puncture biopsy: the results of prostate biopsy were negative in 3 cases. The digital rectal examination found that the prostate volume was Ⅰ or Ⅱ degree large, 10 cases touched hard and the nodule was touched in two cases. Three patients had undergone a previous prostate biopsy, but prostate cancer was not found. All the 17 operations were successfully performed without conversion to open surgery. The surgery time was (85±21) (range from 45 to 120) min, the estimated blood loss was (25±18) (range from5 to 100) ml, the time of intake of liquid diet was (14.3±4.4) h, the intestinal recovery time was (23±10) h, the postoperative activity time was (22±7) h, the drainage duration was (3.7±0.8) d, the postoperative hospital stay was (4.9±1.2) days, and the catheter removal time was (7.4±1.5) days. In the early postoperative period (within 30 days after surgery), no obvious complications occurred. The postoperative final pathology confirmed that all the 17 specimens were prostate cancer. After a median follow-up of 6.5 months, the patient's urinary control rate reached 81.3% at postoperative 1 month, 92.3% at postoperative 3 months after surgery, and the urinary control rate reached 100% at postoperative 6 months. Postoperative PSA value was (0.08±0.08) µg/L, significantly lower than preoperative PSA level (P<0.001). There was significant difference between the preoperative and postoperative QOL (Quality of life) score (57±5 and 47±5 respectively, P<0.001) which indicated that the patients' postoperative quality of life was greatly improved. Conclusions: It is safe and feasible to perform minimally invasive radical prostatectomy without preoperative prostate biopsy for patients with highly suspected prostate cancer by comprehensive diagnostic mode based on modern new imaging technology.

[Analysis of treatment and prognosis of 59 cases of vulvar melanoma].

Objective: To assess the treatment and prognosis of vulvar melanoma. Methods: A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months). Results: (1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy，one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant （P<0.01）. The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups (P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma (P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma (P<0.01). Conclusions: The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.

[Endoscopic combined ultrasound-guided access vs. ultrasound-guided access in endoscopic combined intrarenal surgery].

OBJECTIVE: To compare the outcomes of endoscopic combined ultrasound-guided access (EUGA) with the conventional ultrasound-guided access (UGA) to achieve percutaneous renal access in endoscopic combined intrarenal surgery (ECIRS). METHODS: A retrospective review of 53 patients undergoing ECIRS to treat upper urinary tract calculi between January 2017 and October 2019 was con-ducted. All of the cases were of complex upper urinary tract stones larger than 2 cm in diameter. The com-plex stone situations, such as multiple renal calyces calculi or staghorn calculi necessitated ECIRS. Under general anesthesia, the patients were placed in the galdakao-modified supine valdivia (GMSV) position, thus allowing both antegrade and retrograde accesss. The patients were divided to UGA and EUGA groups according to the protocol of achieving percutaneous renal access. In 28 cases, endoscopic combined ultrasound-guided accesss were obtained. Puncture and dilation were performed under direct flexible ureteroscopic visualization, while percutaneous renal access of 25 cases were performed with the conventional technique employing ultrasound guidance. Demographic and perioperative information, such as stone burden, presence of hydronephrosis and number of calyces involved was compared. Primary outcomes included total operative time, renal access time, repeat puncture, hemoglobin level, perioperative complications, and stone-free rate. RESULTS: No major intra-operative complication was recorded in all the 53 ECRIS. No significant difference was observed between the groups in age and gender. There was no significant difference in body mass index[BMI (29.21±3.14) kg/m2 vs.(28.53±2.56) kg/m2], stone burden (37.68±6.89) mm vs. (35.53±6.52) mm, number of calyces involved 2.72±0.68 vs. 2.86±0.71, presence of hydronephrosis (56.0% vs. 46.4%), total operative time (93.0±12.2) min vs. (96.8±14.2) min, hemoglobin level reduction (6.56±2.16) g/L vs. 97.54±2.64) g/L, stone-free rate (92.0% vs. 92.8%), hospital stay (5.52±0.59) d vs. (5.64±0.62) d, perioperative complication rate (8.0% vs. 7.2%). Two patients in EUGA group experienced perioperative complications (one urinary tract infection and one hematuria) while two patients in UGA group experienced perioperative urinary tract infection. None in both groups received blood transfusion. The patients undergoing EUGA had shorter renal access time [(4.0±0.7) min vs. (6.8±2.6) min, P < 0.01] and less repeat puncture (0 vs. 4 cases, P < 0.05). CONCLUSION: EUGA is an optimal technique to establish percutaneous renal access in ECIRS, which minimizes access time and repeated procedures.