[Abdominal function and appearance of patients after repairing the extensive skin and soft tissue defects in the limbs with two types of lower abdominal tissue flaps].

Objective: To study the abdominal function and appearance of patients after repairing the extensive skin and soft tissue defects in the limbs with two types of lower abdominal tissue flaps. Methods: A retrospective clinical controlled study was conducted. From June 2016 to October 2022, 17 patients with extensive skin and soft tissue defects in the limbs who met the inclusion criteria were admitted to the Department of Bone Hand Microsurgery of Shandong Wendeng Orthopedic Hospital, including 2 males and 15 females, aged 21-60 years, with a defect ranging from 15.0 cm×10.0 cm to 23.0 cm×15.0 cm. According to the applied repair method, the patients were divided into deep inferior epigastric perforator (DIEP) flap group (9 cases) with the defect wound being repaired by the DIEP flap and muscle sparing transverse rectus abdominis myocutaneous (MS-TRAM) flap group (8 cases) with the defect wound being repaired by the MS-TRAM flap. On post surgery day (PSD) 1, 3, 5, 7, and 14, the blood supply of the tissue flaps was evaluated using a self-made tissue flap blood supply evaluation scale. At 12 months after surgery, the patients' satisfaction with the efficacy of tissue flap repair was evaluated using the satisfaction score standard for flap efficacy. Before surgery and at 3 and 12 months after surgery, a self-made abdominal wall strength evaluation scale was used to evaluate the strength of abdominal wall. At 12 months after surgery, a self-made abdominal appearance evaluation scale was used to evaluate the condition of abdominal scars, degree of abdominal symmetry, the appearance and restoration of umbilicus, abdominal protrusion during dressing, and formation of folds on both sides of the abdomen. Data were statistically analyzed with analysis of variance for repeated measurement, independent sample t test, paired sample t test, and Fisher's exact probability test. Results: On PSD 1, 3, 5, 7, and 14, there was no significant change in the blood supply score of tissue flaps of patients in the two groups, and there was no statistically significant difference between the two groups (P>0.05). At 12 months after surgery, the satisfaction ratio of patients in DIEP flap group with tissue flap repair efficacy was 8/9, which was close to 7/8 in MS-TRAM flap group (P>0.05). The preoperative abdominal wall strength of patients between the two groups was similar (P>0.05), while the abdominal wall strength of patients in DIEP flap group was significantly stronger than that in MS-TRAM flap group at 3 and 12 months after surgery (with t values of 3.09 and 3.02, respectively, P<0.05). Compared with the preoperative strength within each group, the abdominal wall strength of patients in DIEP flap group at 3 months after surgery and in MS-TRAM flap group at 3 and 12 months after surgery decreased significantly (with t values of 6.04, 9.71, and 2.91, respectively, P<0.05), which did not change significantly in DIEP flap group at 12 months after surgery (P>0.05). At 12 months after surgery, the scores of abdominal scars, degree of abdominal symmetry, the appearance and restoration of umbilicus, abdominal protrusion during dressing, and formation of folds on both sides of the abdomen of patients were similar between the two groups (P>0.05). Conclusions: Free transplantation of DIEP flap and MS-TRAM flap to repair the extensive skin and soft tissue defects in the limbs can achieve good repair results, including good blood supply of tissue flap and abdominal shape, and the patients' high degree of satisfaction with the efficacy of tissue flap repair. However, DIEP flap is superior to MS-TRAM flap in terms of long-term postoperative abdominal wall strength recovery, showing a broader prospect of application.

[Discussion on two common problems in renal transplantation donor-specificity discrimination of anti-human leukocyte antigen antibody].

Antibody-mediated rejection (AMR) is a key factor affecting the long-term survival of renal allografts. Donor-specific antibody (DSA) is the etiology of AMR. So it is very important to accurately detect DSA. The single antigen bead (SAB) method, which is widely used in clinical practice, is prone to miss DSA detection and underestimate its mean fluorescence intensity (MFI). In this paper, the probability of missed detection of two SAB reagents was calculated by comparing common HLA alleles in China population, and the in vitro effect of antibody cross reaction on MFI value of DSA was revealed. The authors emphasized the clinical significance of the above two problems, tried to manage them by using functional epitope (eplet) analysis and give some clinical examples. Finally, the limitations of this correction method were analyzed.

[Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion].

Objective: To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion. Methods: The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up. Results: The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %. Conclusions: TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

[Multiple pulmonary nodules with interstitial changes].

A 53-year-old female patient with pulmonary nodules for more than 3 years was admitted to Beijing Chao-Yang Hospital because of cough and sputum with shortness of breath after exercise for 4 months. In the first two and a half years, her pulmonary nodules remained stable, after that the nodules increased obviously with interstitial changes. After admission, a venous thromboembolic (VTE) event was quickly detected with a marked increase in D-dimer. Then, based on the clues of VTE examination, bronchoscopy, gastroscope, positron emission tomography-CT, head magnetic resonance and other examinations were performed. The final pathological diagnosis was lung adenocarcinoma, mainly solid with mucus secretion, with mediastinal hilar lymph node metastasis, intrapulmonary metastasis and gastric metastasis. Gene detection of lung and stomach histopathological tissues showed positive EML4-ALK fusion gene. The patient received therapies with crizotinib, alectinib in sequence and anticoagulation. After 20-month treatment, a telephone follow-up showed that there was no significant limitation in her daily activities.

[Establishment and comparison of three human multiple myeloma cell line transplantation models in mice].

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.

Association of Arterial Stiffness with Functional Disability and Mobility Limitation: The Rugao Longitudinal Ageing Study.

OBJECTIVES: Arterial stiffness is a common issue that may represent an indicator of vascular ageing. We aimed to investigate the association of arterial stiffness with the risk of functional disability and mobility limitation in older adults. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A total of 1699 older adults from the Rugao Longitudinal Ageing Study were included and analysed. MEASUREMENTS: Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Functional disability and mobility limitation were evaluated by the activities of daily living and the Timed Up and Go test, respectively. The associations of baPWV and risk of functional disability and mobility limitation were analysed using logistic regression models. Restricted cubic spline regressions were applied to estimate the possible nonlinear relationships between them. RESULTS: During the 3.5-year follow-up, 97 (10.00%) and 285 (31.11%) individuals were defined as new-onset functional disability and mobility limitation, respectively. After adjusting for confounding factors, elevated baPWV was significantly associated with a higher risk of incident functional disability (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.06-1.31) and mobility limitation (OR 1.08, 95% CI 1.01-1.16). Additionally, consistent results were obtained from the stratified analyses of the different subgroups. Multivariable restricted cubic spline regression analysis further demonstrated that a near-linear association occurred between baPWV and the risk of incident functional disability and mobility limitation (P-overall < 0.01, P-nonlinear >0.05). CONCLUSION: Arterial stiffness, as assessed by baPWV, was associated with the risk of functional disability and mobility limitation in this community-based cohort, and these associations were nearly linear.

[Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice].

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1ß levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1ß levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.

[The effect of red blood cell folate on the prognosis of high-risk human papillomavirus infection: a community-based cohort study].

Objective: To investigate the effect of red blood cell folate on the prognosis of high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 564 participants with low-grade cervical intraepithelial neoplasias (CINⅠ) were selected from the community-based married women cohort established in 2014. The general baseline information and factors related to HPV infection were collected. Meanwhile, HPV genotyping and levels of folate were measured. The subjects were divided into different levels of exposure group according to the folate levels and followed up for 24 months to observe the changes of HR-HPV infection status. There were four changes, including persistent infection, infection turned negative, from negative to positive and constant negative by comparing HR-HPV infection status at baseline and follow-up to 24 months. Results: 483 participators completed 24 months of follow-up observation, with a follow-up rate of 85.64% (483/564). The rates of persistent infection, infection turned negative, from negative to positive, and the constant negative were 52.45% (75/143), 47.55% (68/143), 19.71% (67/340), 80.29% (273/340), respectively. Our results demonstrated that the risk of persistent infection (aRR=2.50, 95%CI: 1.55-4.02) and from negative to positive (aRR=4.55, 95%CI: 2.52-8.23) in the low level of folate were significantly higher than that in the high level of folate, especially the risk of homotype persistent infection (aRR=2.72, 95%CI: 1.51-4.90). The risk of persistent infection (trend χ2=20.62, P<0.001), from negative to positive (trend χ2=31.76, P<0.001), persistent homotypic infection (trend χ2=20.09, P<0.001) increased with the decrease of red blood cell folate level. On the contrary, no similar results were found in persistent heterotypic infection. Conclusions: A low level of red blood cell folate could increase the risk of HR-HPV persistent infection and from negative to positive. In women with HR-HPV infection, the risk of persistent homotypic infection is higher.

Grain size dependent high-pressure elastic properties of ultrafine micro/nanocrystalline grossular.

We have performed sound velocity and unit cell volume measurements of three synthetic, ultrafine micro/nanocrystalline grossular samples up to 50 GPa using Brillouin spectroscopy and synchrotron X-ray diffraction. The samples are characterized by average grain sizes of 90 nm, 93 nm and 179 nm (hereinafter referred to as samples Gr90, Gr93, and Gr179, respectively). The experimentally determined sound velocities and elastic properties of Gr179 sample are comparable with previous measurements, but slightly higher than those of Gr90 and Gr93 under ambient conditions. However, the differences diminish with increasing pressure, and the velocity crossover eventually takes place at approximately 20-30 GPa. The X-ray diffraction peaks of the ultrafine micro/nanocrystalline grossular samples significantly broaden between 15-40 GPa, especially for Gr179. The velocity or elasticity crossover observed at pressures over 30 GPa might be explained by different grain size reduction and/or inhomogeneous strain within the individual grains for the three grossular samples, which is supported by both the pressure-induced peak broadening observed in the X-ray diffraction experiments and transmission electron microscopy observations. The elastic behavior of ultrafine micro/nanocrystalline silicates, in this case, grossular, is both grain size and pressure dependent.

[Effect of dietary water-soluble vitamins on the poor prognosis of low-grade cervical intraepithelial neoplasia-a prospective cohort study].

Objective: To explore the effect of dietary water-soluble vitamins on the poor prognosis of low-grade cervical intraepithelial neoplasia (CINⅠ). Methods: A total of 564 participants with CINⅠ were selected from a community-based married women cohort established in 2014. The general baseline information was collected, and HPV genotyping was detected. A food frequency questionnaire was used to investigate dietary water-soluble vitamins' consumption and determine their exposure levels. The follow-up program was carried out for 12 months, and the regression, persistence, and progression of CINⅠ was determined according to histopathological results at 12-month. Results: The low-levels of dietary water-soluble vitamins could promote CINⅠ's persistence and progression, showing the increasing tendency of CINⅠ poor prognosis with the decrease of water-soluble vitamin levels. Especially folate, VB1, VB2, VB6, niacin, biotin, and VC (RR values were 15.22, 1.86, 1.92, 2.11, 2.98, 2.14, 2.19, respectively) played an important role. Considering the status of high-risk human papillomavirus (HR-HPV) infection, our results showed that the low levels of folate, niacin, biotin could promote the poor prognosis of CINⅠ. Conclusions: The low-level of dietary water-soluble vitamins could facilitate the poor prognosis of CINⅠ. In addition, folate, niacin, biotin were more effective on HR-HPV positive women.

[Prognosis of high-risk HPV infection and its influences by vaginal micro-environmental factors].

Objective: To describe the characteristics of high-risk human papillomavirus (HR-HPV) infection and its influences by vaginal micro-environmental factors. Methods: A total of 421 women with HR-HPV infection and normal cervix diagnosed by pathology were selected from a community cohort established earlier by our research group for a 24-month follow-up. The baseline data were collected at enrollment. The vaginal micro-environmental factors were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis. And the HPV was detected by using the flow-through hybridization technology. According to the HR-HPV infection status in baseline and 24 months of follow-up, with the prognosis characteristics of HR-HPV infection described, the impact of vaginal micro-environmental factors on the prognosis of HR-HPV infection was explored as well. Results: Among 390 HR-HPV infected women who completed 24 months of follow-up, the top five types of persistent HR-HPV infection rate appeared as HPV16 (24.1%), HPV58 (22.2%), HPV53 (21.7%), HPV52 (20.0%), and HPV39 (11.8%), respectively. The results showed that women with abnormal vaginal pH (aOR=1.74, 95%CI: 1.08-2.80), abnormal neuraminidase (aOR=2.70, 95%CI: 1.52-4.83), or abnormal leucocyte esterase (aOR=3.41, 95%CI: 2.13-5.44), the risk of HR-HPV persistent infection increased. The abnormalities of neuraminidase and leukocyte esterase could increase the risk of persistent infection of homotype and heterotypic HR-HPV. Conclusions: HPV16 was prone to persistent infection. Abnormalities of vaginal pH, neuraminidase, and leukocyte esterase might increase the risk of HR-HPV persistent infection. Both the abnormalities of neuraminidase and leukocyte esterase play an essential role in the HR-HPV persistent infection.

[The optimal model of diagnosis to low-grade cervical intraepithelial neoplasia by combined detecting vaginal micro-environmental factors, based on the high-risk HPV infection].

Objective: To investigate the diagnostic value of different vaginal micro-environmental factors in low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and determine the optimal model in high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 926 women, including 623 with normal cervical (NC) condition and 303 CINⅠ patients, had undergone pathological examinations, and were enrolled in the study. All the women were from a community previously established cohort. Vaginal cleanliness, pH, H2O2, ß-glucuronidase, coagulase, sialidase, and leukocyte esterase (LE) were detected by the combined detection method aerobic vaginitis/bacterial vaginosis in vaginal secretions. HPV genotyping was performed by using the flow-through hybridization technology. The data were analyzed by SAS 9.2 and SPSS 23.0. Results: The vaginal cleanliness, pH, sialidase, and LE were determined as the representative vaginal micro-environment factors by principal component analysis. Based on logistic regression theory to analyze the ROC curve, the results showed that the highest sensitivity was with pH value (76.2%), and the highest specificity was with sialidase (90.9%). The area under ROC curve were higher in combination detection modes of sialidase+LE (0.714), pH+sialidase+LE (0.719), vaginal cleanness+sialidase+LE (0.713) and pH+vaginal cleanness+sialidase+LE (0.709). According to HR-HPV infection status, the TOPSIS method was used to analyze the combined detection optimal model. Specifically, we found that the best diagnostic model was pH+sialidase +LE (Ci=0.585) in the HR-HPV positive group and vaginal cleanness+sialidase+LE (Ci=0.641) in the negative group. Conclusions: The combined detection of vaginal microenvironment factors could be used for auxiliary diagnosis for CINⅠ. It would be more effective when detecting pH, sialidase, and LE in HR-HPV positive women while vaginal cleanness, sialidase, and LE in HR-HPV negative women at the same time.

[Effects of polycyclic aromatic hydrocarbons exposure on prognosis of high risk human papillomavirus infection: a prospective cohort study].

Objective: To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) exposure on the prognosis of high risk human papillomavirus (HR-HPV) infection. Methods: In this prospective study, 564 patients with low-grade cervical intraepithelial neoplasia confirmed by pathology were selected from the natural cohort population established by our research group in Shanxi province in 2014. Based on the baseline data of demographic characteristics and factors related to HPV infection, the concentrations of 1-hydroxypyrene in urine samples of the patients were determined by high performance liquid chromatography to define the exposure level of PAHs. At baseline survey and follow-up after 24 months, flow-through hybridization was used to detect HPV infection types, and to evaluate the prognosis of HR-HPV (persistent infection, negative conversion, positive conversion and persistent negative status). Results: Of the 564 subjects, 483 completed the follow-up, with a follow-up rate of 85.6% (483/564). Among them, the persistent infection rate was 52.4% (75/143), the persistent homotype infection rate was 35.7% (51/143), the negative conversion rate was 47.6% (68/143), the positive conversion rate was 19.7% (67/340), and the persistent negative rate was 80.3% (273/340). The follow-up results showed that the persistent infection rate (aRR=3.22, 95%CI: 1.85-5.62) and positive conversion rate (aRR=2.84, 95%CI: 1.64-4.94) of HR-HPV in high PAHs exposure group were higher than those in low PAHs exposure group, while the persistent negative rate (aRR=0.55, 95% CI: 0.43-0.70) of HR-HPV in high PAHs exposure group were lower than those in low PAHs exposure group. Based on restrictive cubic spline analysis, the results showed that the effects of PAHs exposure on persistent HR-HPV infection and persistent homotype infection showed an ascending linear dose-response relationship, while on HR-HPV positive conversion and persistent negative status showed an ascending and declining nonlinear dose-response relationship respectively (P<0.01). Conclusions: High PAHs exposure could promote persistent HR-HPV infection and persistent homotypic infection. Reducing PAHs exposure might conducive to HR-HPV continuous negative maintenance. Active prevention and control of PAHs exposure is of great significance to prevent HR-HPV infection and persistent infection.

[Relationship between serum folate and CIN1 prognosis and its interaction with HR-HPV infection].

Objective: To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection. Methods: From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection. Results: Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant (Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group (P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning (OR=0.422, 95%CI: 0.238-0.750), frequency of changing underwear (OR=0.574, 95%CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95%CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95%CI: 4.024-17.445), HR-HPV infection (OR=1.852, 95%CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95%CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95%CI: 0.279-0.824), synergy index was 2.632 (95%CI: 1.239-5.588), aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95%CI: 4.878-16.807). Conclusion: Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

Experimental semi-autonomous eigensolver using reinforcement learning.

The characterization of observables, expressed via Hermitian operators, is a crucial task in quantum mechanics. For this reason, an eigensolver is a fundamental algorithm for any quantum technology. In this work, we implement a semi-autonomous algorithm to obtain an approximation of the eigenvectors of an arbitrary Hermitian operator using the IBM quantum computer. To this end, we only use single-shot measurements and pseudo-random changes handled by a feedback loop, reducing the number of measures in the system. Due to the classical feedback loop, this algorithm can be cast into the reinforcement learning paradigm. Using this algorithm, for a single-qubit observable, we obtain both eigenvectors with fidelities over 0.97 with around 200 single-shot measurements. For two-qubits observables, we get fidelities over 0.91 with around 1500 single-shot measurements for the four eigenvectors, which is a comparatively low resource demand, suitable for current devices. This work is useful to the development of quantum devices able to decide with partial information, which helps to implement future technologies in quantum artificial intelligence.

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.