Likelihood-based inference under nonconvex boundary constraints.

Likelihood-based inference under nonconvex constraints on model parameters has become increasingly common in biomedical research. In this paper, we establish large-sample properties of the maximum likelihood estimator when the true parameter value lies at the boundary of a nonconvex parameter space. We further derive the asymptotic distribution of the likelihood ratio test statistic under nonconvex constraints on model parameters. A general Monte Carlo procedure for generating the limiting distribution is provided. The theoretical results are demonstrated by five examples in Anderson's stereotype logistic regression model, genetic association studies, gene-environment interaction tests, cost-constrained linear regression and fairness-constrained linear regression.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens.

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

[Role of innate lymphoid cells in oral squamous cell carcinoma microenvironment].

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. It has a high incidence, strong invasion ability, easy metastasis, poor curative effect, and poor prognosis. Innate lymphoid cells (ILCs) are an important part of immune cells located in the mucosal barrier, which play an important role in the occurrence, development and outcome of tumors. ILCs are the key cells for decoding the regulatory mechanism of tumor microenvironment and the signatures for tumor progression. This paper reviewed the latest progress on ILCs, summarized the possible characteristics and functions of ILCs in the microenvironment of OSCC, and explored the relationship between ILCs and the occurrence, development and immunotherapy of OSCC.

Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[Annual review of bronchiectasis research in 2023].

This review focuses on the latest advances in bronchiectasis from October 1st, 2022 to September 30th, 2023, including the etiology, diagnosis, treatment, comorbidities, and management of bronchiectasis in order to provide a reference in clinical diagnosis and treatment, and future research of bronchiectasis for domestic peers.

[Comparison of short-term safety of two anastomotic techniques when resecting Siewert type II adenocarcinoma of the esophagogastric junction: a multicenter retrospective cohort study].

Objective: In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups. Results: There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant (t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ²=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences (Z=0.406, P=0.685). Conclusions: Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

The Therapeutic Effects of Noninvasive Brain Stimulation Combined with Cognitive Training in Elders with Alzheimer's Disease or Amnesic Mild Cognitive Impairment.

BACKGROUND: Recent studies have indicated that noninvasive brain stimulation combined with cognitive interval (NIBS-CI) improved cognitive function in people with Alzheimer's disease (AD) or Amnesic mild cognitive impairment (a-MCI). While previous interventions have demonstrated that a single targeted cognitive intervention can improve cognitive function, the outcomes of using both interventions simultaneously are less well-established. Therefore, this study aims to perform a meta-analysis to determine the effectiveness of NIBS-CI in treating cognitive impairment associated with AD and a-MCI, with the goal of obtaining novel insights into this combined intervention. METHODS: PubMed, Web of Science, ProQuest and Central Cochrane library databases were searched up to December 2022. The primary cognitive outcomes were extracted from the included article. A mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval were calculated by using random-effect models. RESULTS: Twelve studies with a total of 587 AD patients were included. The findings demonstrated that NIBS-CI significantly improved cognitive function of AD patients in cognitive outcomes (SMD = -0.52, 95%CI (-0. 93, -0.11)) and ADAS-COG (MD = -1.16, 95%CI (-1.69, -0.63)). The pooled results showed that NIBS-CI did not improve cognitive function of AD patients in short-time memory (SMD = 0.057, 95%CI (-0.13, 0.25), P = 0.56) and long-time memory (SMD = 0.001, 95%CI (-0.20, 0.20), P = 0.99). CONCLUSIONS: There is evidence for a positive effect of NIBS-CI on overall cognitive function of AD and a-MCI. Considering the limited sample size, it is important to interpret the findings related to memory with caution. To obtain more robust results, future studies should be conducted with larger sample sizes and incorporate objective neurophysiological and neuroimaging tools. These methodological enhancements will allow for a better understanding of the therapeutic targets and provide a more comprehensive assessment of the effects of NIBS-CI treatment.

[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

Effects of endometriosis on pregnancy outcomes in Fujian province.

OBJECTIVE: Endometriosis is a common gynecological disease, affecting 5 to 10% of women of childbearing age. We analyzed pregnancy complications and neonatal outcomes of patients with pregnancies complicated with endometriosis. The aim of the study was to explore the effects of endometriosis on pregnancy and to evaluate the potential pregnancy risks associated with this disease. PATIENTS AND METHODS: The retrospective study included 3,809 parturients who were routinely examined, hospitalized and underwent cesarean section delivery in Fujian Maternal and Child Health Hospital from January 2014 to December 2020. Among them, 1,026 parturients were diagnosed with endometriosis after the cesarean section (endometriosis group), and 2,783 parturients without endometriosis comprised the control group. The endometriosis group was further divided into subgroups according to the severity of the disease: 882 parturients with stage Ⅰ or Ⅱ of endometriosis, and 144 parturients with stage Ⅲ or Ⅳ of endometriosis. General data of all patients and medical records of pregnancy complications and neonatal outcomes for each group were collected and retrospectively analyzed. RESULTS: There were no statistically significant differences in the age, gestational age, gestation, and parity times between all groups (p>0.05). The incidence of preeclampsia and placenta previa in the endometriosis group was higher than that in the control group (p<0.05). There was no significant difference in rates of other pregnancy complications, such as chronic hypertension with pregnancy, preeclampsia with chronic hypertension, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, gestational diabetes mellitus (GDM), pregestational diabetes mellitus (PGDM), intrahepatic cholestasis of pregnancy (ICP), premature rupture of membranes or placental abruption between the two groups. The incidence of placenta previa in the group of patients with stage III/IV endometriosis was higher than in patients with stage I/II endometriosis (p<0.05). However, there was no significant difference in the incidence of other pregnancy complications. The amount of postpartum hemorrhage (1,000-1,500 ml) in the endometriosis group was greater than that in the control group, and the difference was statistically significant (p<0.05). However, there was no significant difference in the incidence of postpartum hemorrhage in patients with pregnancies complicated with endometriosis at different stages. CONCLUSIONS: In pregnant women, endometriosis is associated with an increased incidence of placenta previa that correlates with the severity of the disease. Pregnant women with endometriosis have higher rates of preeclampsia and postpartum hemorrhage, compared to women without endometriosis.

[Application value of questionnaires in the screening obstructive sleep apnea syndrome in pregnancy across trimesters].

Objective: To evaluate the clinical utility value of questionnaires of Berlin, STOP, STOP-Bang (SBQ), Epworth Sleepiness Scale (ESS) in screening obstructive sleep apnea syndrome (OSAS) in pregnant women of different trimesters. Methods: Consecutive pregnant women at high risk for OSAS were enrolled from January, 2021 to April, 2022 at the obstetric clinic of Peking University People's Hospital. They completed questionnaires of Berlin, STOP, SBQ, ESS and also underwent an overnight polysomnography (PSG). To evaluate the accuracy of questionnaires of Berlin, STOP, SBQ, ESS, sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics (ROC) curve of these questionnaires in pregnancy across trimesters (Pregnancy 1-15 weeks was the first stage, pregnancy 16-27 weeks was the second stage, and pregnancy 28-40 weeks was the third stage) were calculated. Results: A total of 100 pregnant women [(34.5±4.3) years old (26-46 years old)] were included in this study, including 20, 35 and 45 pregnant women in the first, second and third trimester of pregnancy, respectively. Based on PSG results, 45 (45%) of 100 pregnant women were diagnosed with OSAS. The overall predictive values of the four questionnaires were not good, area under[AUC(95%CI)] the ROC curve ESS, Berlin questionnaire STOP and SBQ were 0.54(0.43, 0.66), 0.59 (0.47, 0.70), 0.62(0.51, 0.73) and 0.61 (0.49, 0.72), respectively, sensitivity was 35.6%, 65.9%, 48.9%, 28.9%, specificity was 71.7%, 52.5%, 73.6%, 92.5%. When categorized according to trimesters, the predicted values of the four questionnaires increased in the first trimester, the AUC (95%CI) of STOP questionnaire was 0.81 (0.61, 1.00), sensitivity was 75.0%, specificity was 87.5%. Conclusion: The overall predictive power of the four screening questionnaires is limited in pregnant women. But predictive value of STOP questionnaire is acceptable in the first trimester.

First observation of fluid-like eddy-dominant bursty bulk flow turbulence in the Earth's tail plasma sheet.

Turbulence is a ubiquitous phenomenon in neutral and conductive fluids. According to classical theory, turbulence is a rotating flow containing vortices of different scales. Eddies play a fundamental role in the nonlinear cascade of kinetic energy at different scales in turbulent flow. In conductive fluids, the Alfvénic/kinetic Alfvénic wave (AW/KAW) is the new "cell" of magnetohydrodynamic (MHD) turbulence (frozen-in condition). Wave energy, which has equal kinetic and magnetic energy, is redistributed among multiple-scale Fourier modes and transferred from the large MHD scale to the small kinetic scale through the collision of counter-propagating Alfvénic wave packages propagating along the magnetic field line. Fluid-like eddy-dominant plasma flow turbulence has never been found in space since the launch of the first satellite in 1957. In this paper, we report the first observation of eddy-dominant turbulence within magnetic reconnection-generated fast flow in the Earth's tail plasma sheet by the Magnetospheric Multiscale Spacecraft (MMS). In eddy-dominant turbulent reconnection jet, ions dominate the flow field while electrons dominate current and magnetic fluctuations. Our findings shed new light on the nonlinear kinetic and magnetic energy cascade in MHD turbulence.

[Effects of electric welding on hearing loss and respiratory damage].

Objective: To investigate the occupational health status of electric welding workers and explore the effects of electric welding on hearing loss and respiratory damage. Methods: From August to December 2021, the cluster sampling method was used to select workers from an automobile manufacturer in Guangzhou City as research subjects: 636 welding workers in the welding workshop as the welding group, 757 assembly workers in the engine workshop and the final assembly workshop exposed to pure noise as the assembly group. Occupational disease hazard factors were detected for welding positions and assembly positions, and occupational health examination was carried out for research subjects. The occupational health status, the trends of hearing loss and respiratory abnormalities with working age were compared and analyzed between the two groups. Binary logistic regression was used to analyze the association between hearing loss and respiratory abnormalities in welding workers. Results: The excess rates of welding fumes, manganese and its compounds in the welding position were both 9.68% (3/31). Its noise exposure intensity [ (85.36±2.68) dB (A) ] and excess rate [48.39% (15/31) ] were not significantly different from those in the assembly position [ (84.86±3.28) dB (A) and 43.24% (16/37) ] (P>0.05). The results of the occupational health examination showed that the detection rates of hearing loss, digital radiography (DR) chest X-ray abnormality, alanine aminotransferase abnormality, deazelaic aminotransferase abnormality and white blood cell count abnormality of workers in the welding group were higher than those in the assembly group (P<0.05). The detection rates of hearing loss, DR chest X-ray abnormality, pulmonary ventilation abnormality in the welding group and the detection rate of hearing loss in the assembly group increased with the working age of the workers (P<0.05). The hearing loss detection rate and DR chest X-ray abnormality detection rate of the workers with ≥9 years working age in the welding group were both higher than those in the assembly group workers with same working age (P<0.05). The binary logistic regression analysis showed that abnormal pulmonary ventilation and abnormal DR chest X-ray were the risk factors for hearing loss in welding workers (OR=10.83, 95%CI: 7.31-16.06; OR=16.59, 95%CI: 5.72-48.10; P<0.05) . Conclusion: Hearing loss and respiratory damage are prominent problems among welding workers, and the detection rates of abnormality increase with the working age of the workers. Hearing loss in welding workers is associated with abnormal pulmonary ventilation and abnormal DR chest X-ray.

[Relationships between hypertensive disorders in pregnancy and obstructive sleep apnea syndrome].

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m2) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.

[Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study].

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

DNA binding properties and cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone.

OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.

The diagnostic accuracy of the IFLIP system for binocular visual function anomalies assessment.

OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of the intelligent flipper (IFLIP) system in identifying binocular vision anomalies. PATIENTS AND METHODS: This study comprised 70 participants aged 18 to 22. Participants underwent comprehensive eye assessments, including measurement of visual acuity, refraction, far and near cover test, stereopsis, and worth four dot test. The manual accommodation amplitude and facility, as well as the IFLIP system test, were also evaluated. The correlation between the indices of the IFLIP and manual accommodation tests was analyzed using multiple regression models, and the diagnostic ability of the IFLIP was characterized using Receiver Operating Curve (ROC) analysis. The significance level was 0.05. RESULTS: The mean age of the 70 participants was 20.03±0.78 years. The mean manual and IFLIP accommodation facilities were 12.00±3.70 cycle per minute (CPM) and 10.01±2.77 CPM, respectively. No correlation was found between the indices of the IFLIP system and manual accommodative amplitude. However, the regression model showed that the contraction/relaxation ratio of the IFLIP system was positively correlated to the manual accommodation facility, and the average contraction time was negatively correlated with the manual accommodation facility. The ROC analysis proposed a cut-off of 10.15 CPM monocularly for the IFLIP accommodation facility assessment. CONCLUSIONS: This study indicated that the parameters obtained by the IFLIP system and the manual accommodation facility were comparable, and the IFLIP system had good sensitivity and specificity in the assessment of the accommodation facility, thus may serve as a promising tool for screening and diagnosis of binocular visual function anomalies in clinical and community settings.

[The prospect and challenge of liquid biopsy in the diagnosis and treatment of chest malignancy].

In recent years, the incidence of chest malignant tumors in China has increased year by year, which has seriously threatened the health problems of people. Among them, early screening and intervention of patients with chest malignancies is the key to cancer prevention. Early detection, early diagnosis, and early treatment as the "three early prevention" of clinical practice are conducive to improve the survival rate of tumor patients. As a non-invasive and real-time reflection of tumor status, liquid biopsy has gradually received attention in clinical diagnosis and treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as liquid biopsy "Three carriages" are not only widely used in the diagnosis, monitoring and prognostic evaluation of chest malignancies, but also face many unknown challenges. In this article, the application of liquid biopsy in chest malignancies in recent years is elaborated in detail, which provides a reference for the formulation of clinical tumor prevention and diagnosis and treatment strategies.