Mechanistic Study on Palladium-Catalyzed Regioselective Oxidative Amination: Roles of Ammonium Salts.

Anti-Markovnikov selective oxidative amination reaction with simple alkenes is particularly promising but challenging because of the inherent electronic effect of the alkene substrate which is in favor of the Markovnikov product. In a recently reported Pd-catalyzed anti-Markovnikov oxidative amination reaction, the addition of quaternary ammonium salts is shown to be critical. We performed a comprehensive DFT study to elucidate the reaction mechanism and the origin of the regioselectivity, as well as the roles of the ammonium salts. Our results show that without and with the ammonium salts the reaction mechanisms are different. Detailed analyses indicate that the steric effects account for the switch of regioselectivity. The roles of the quaternary ammonium salts have been elucidated: (1) Me4NOAc plays the role of base in deprotonating the phthalimide and allows the reaction to proceed through a trans-aminopalladation mechanism; (2) Me4NCl facilitates the thermodynamically favorable transformation of Pd(OAc)2 to the palladate ([Pd(AcO)2Cl2]2-), which lessens the polarity of the carbon-carbon double bond, minimizes the inherent electronic effects, and leads to a steric-effect-controlled reaction; (3) Me4NCl is essential in decreasing the activation barrier in the rate-determining ligand exchange step by Cl- acting as a better leaving group (compared to AcO-).

Vitamin D deficiency may predict a poorer outcome of IgA nephropathy.

BACKGROUND: Experimental studies showed that 25-hydroxy-vitamin D [25(OH)D] deficiency (defined as 25-hydroxy-vitamin D < 15 ng/ml) has been associated with CKD progression. Patients with IgA nephropathy have an exceptionally high rate of severe 25(OH)D deficiency; however, it is not known whether this deficiency is a risk factor for progression of IgA nephropathy. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and certain clinical parameters and renal histologic lesions in the patients with IgA nephropathy, and to evaluate whether the 25(OH)D level could be a good prognostic marker for IgA nephropathy progression. METHODS: A total of 105 patients with biopsy-proven IgA nephropathy were enrolled between 2012 and 2015. The circulating concentration of 25(OH)D was determined using serum samples collected at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; a 30 % or more decline compared to the baseline). RESULTS: Mean eGFR decreased and proteinuria worsened proportionally as circulating 25(OH)D decreased (P < 0.05). The 25(OH)D deficiency was correlated with a higher tubulointerstitial score by the Oxford classification (P = 0.008). The risk for reaching the primary endpoint was significantly higher in the patients with a 25(OH)D deficiency compared to those with a higher level of 25(OH)D (P = 0.001). As evaluated using the Cox proportional hazards model, 25(OH)D deficiency was found to be an independent risk factor for renal progression [HR 5.99, 95 % confidence intervals (CIs) 1.59-22.54, P = 0.008]. CONCLUSION: A 25(OH)D deficiency at baseline is significantly correlated with poorer clinical outcomes and more sever renal pathological features, and low levels of 25(OH)D at baseline were strongly associated with increased risk of renal progression in IgAN.

Effect of active vitamin D on cardiovascular outcomes in predialysis chronic kidney diseases: A systematic review and meta-analysis.

AIM: Vitamin D deficient patients present an increased risk of cardiovascular disease. We conducted this systematic review and meta-analysis to evaluate the effect of active vitamin D analogue on cardiovascular outcomes in predialysis chronic kidney disease. METHODS: Pubmed, Embase, the Cochrane Library, CNKI, and article reference lists were searched for randomized controlled trials (RCTs) that compared active vitamin D analogues with placebo or no treatment for patients with predialysis chronic kidney disease. A meta-analysis was conducted using the standard methods consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Reviewer Manager Software, ver. 5.2, was used. RESULTS: Seven RCTs (five studies with paricalcitol and two studies with calcitriol, 731 patients) were included. Compared with control groups, active vitamin D reduced the incidence of cardiovascular events (RR, 0.27; 95% CI, 0.13-0.59), induced an increase in those with proteinuria reduction (RR, 1.9; 95% CI, 1.34-2.71), but did not alter left ventricular mass index and systolic function (MD, 0.42 g/m2.7 ; 95% CI, -0.23-1.07 g/m2.7 , P = 0.21 for left ventricular mass index and MD, -0.33; 95% CI, -0.74-0.07, P = 0.1 for left ventricular ejection fraction). Neither systolic blood pressure nor diastolic blood pressure was reduced by active vitamin D (MD, 0.3 mmHg; 95% CI, -4.95-5.56 mmHg; MD, -0.24 mmHg; 95% CI: -6.21-5.72 mmHg, respectively). Increased probability of hypercalcaemia after paricalcitol therapy was found (RR, 7.85; 95% CI, 2.92-21.10). CONCLUSION: Active vitamin D reduced the incidence of cardiovascular events and induced a reduction in proteinuria, but its long-term effect on cardiac structure and function needed further confirmation. Increased probability of hypercalcaemia after paricalcitol therapy was found.

Prevalence and risk factors associated with chronic kidney disease in a Zhuang ethnic minority area in China.

AIM: Numerous studies have examined and reported a high prevalence of chronic kidney disease (CKD) in the general population in various countries including China. However, the situation may be different in undeveloped rural minority regions in China because of China's economic diversity. The aim of the present study was to estimate the prevalence of CKD and to analyze its associated factors in a Zhuang ethnic minority area in Southwest China. METHODS: A cross-sectional survey of a rural minority area populated by people of Zhuang ethnicity in Southwest China using multistage, cluster random sampling methods was performed. The prevalence of indicators of kidney damage and CKD were calculated and risk factors associated with the presence of CKD were analyzed. RESULTS: In total, 7588 people participated in the study. After adjustment for age and gender, the prevalence of albuminuria, haematuria and reduced estimated glomerular filtration rate were 2.7%, 3.7%, and 2.2%, respectively. After adjustment for age and gender, the prevalence of CKD was 8.3%, while recognition of the disease was 3.6%. Independent risk factors associated with CKD were age, gender, and hypertension. Risk factors independently associated with kidney damage were age, gender, hyperuricaemia, and hypertension. CONCLUSION: Our data exhibited a lower prevalence and awareness of CKD in undeveloped rural minority regions, especially exhibited a low prevalence of albuminuria. This result attributed to the low prevalence of metabolic disorders in the local region. Risk factors associated with CKD in our study is similar to surveys in other regions of China.

Outcome of laparoscopy-guided hysteroscopic tubal catheterization for infertility due to proximal tubal obstruction.

STUDY OBJECTIVE: To determine pregnancy outcomes after laparoscopy-guided hysteroscopic tubal catheterization and to report its role in the era of in vitro fertilization. DESIGN: Clinical cases series (Canadian Task Force classification II-3). SETTING: Reproductive surgery center. PATIENTS: Patients with unilateral or bilateral proximal tubal obstruction as the only cause of infertility were included. INTERVENTIONS: Laparoscopy-guided hysteroscopic tubal catheterization. MEASUREMENTS AND MAIN RESULTS: Only the first spontaneous conception was considered. Cumulative conception rate (CCR) was calculated using Kaplan-Meier survival analysis. Of 168 women included, 107 (63.7%) had bilateral proximal obstruction and 61 (36.3%) had unilateral obstruction. The successful recanalization rate was 54.2% per tube and 61.9% per patient. In the 93 patients in whom at least 1 fallopian tube was successfully recanalized, 40 spontaneous pregnancies (43.0%) occurred within 24 months, of which 35 (37.6%) were intrauterine pregnancies and 28 (30.1%) resulted in live births. The CCR was 37.6% at 1 year and 43.7% at 2 years. Patients with unilateral obstruction in whom cannulation was successful had the highest CCR (60.7% at 2 years). CONCLUSION: Successful tubal cannulation led to significant improvement in the pregnancy rate, which suggests that women with a proximal tubal block could be considered for laparoscopy-guided hysteroscopic cannulation, which is still a viable alternative to in vitro fertilization.

Does ambient air pollutants increase the risk of fetal loss? A case-control study.

OBJECTIVE: To examine the associations between the ambient air pollution and early fetal loss. STUDY DESIGN: A retrospective case-control study was conducted. 959 fetal losses and 959 normal intrauterine pregnancies within 14 weeks of pregnancy in 15 general or obstetrics and gynecology hospitals were selected into case and control groups, respectively. Data based on hospital records and national pollution monitor station records were collected. Logistic regression model was conducted to examine the associations between 4 ambient air pollutants (SO2, PM10, NO2 and TSP) exposures and fetal loss. RESULTS: The ratio of fetal loss to termination of pregnancy for heating months (2.28 %) was significantly (P < 0.001) higher than that for the non-heating months (1.77 %). Logistic regression suggested that fetal loss within 14 weeks was associated with higher exposure to SO2 (OR = 19.76, 95 % CI 2.34-166.71) and TSP (OR = 2.04, 95 % CI 1.01-4.13) in the first month of pregnancy. CONCLUSION: Exposure to high levels of SO2 and TSP during the first month of pregnancy was associated with an increased risk of fetal loss in early pregnancy.

Red blood cell distribution width to albumin ratio associates with prevalence and long-term diabetes mellitus prognosis: an overview of NHANES 1999-2020 data.

Background: Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality. Methods: Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis. Results: Among non-DM (n=30,404) and DM (n=10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead (n=2,411) and surviving (n=6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width. Conclusions: The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients.

Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis.

BACKGROUND: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.

Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis.

AIM: Both enalapril and losartan are effective and widely used in patients with chronic kidney disease (CKD). This review aimed to evaluate the benefits of enalapril and losartan in adults with CKD. METHODS: PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, without language limitations, for randomized controlled trials (RCT), in which enalapril and losartan were compared in adults with CKD. Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, ver. 5.2, was used for meta-analysis. RESULTS: Of 318 citations retrieved, 17 RCT (14 parallel-group and three cross-over) met our inclusion criteria. The pooled analysis for parallel RCT showed that the effects of enalapril and losartan on blood pressure, renal function and serum uric acid (UA) were similar. Meta-analysis indicated that patients taking enalapril had a higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11-7.48; P=0.03). Sensitivity analysis showed good robustness of these findings. CONCLUSION: Enalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes.

[Related factors associated with pelvic adhesion and its influence on fallopian tube recanalization in infertile patients].

OBJECTIVE: To investigate factors with pelvic adhesions and the effect of different degrees pelvic adhesions on fallopian tube recanalization in infertile patients. METHODS: Total of 527 infertile patients undergoing hysteroscopy and laparoscopic surgery in Affiliated Hospital of Chinese People's Armed Police Forces Logistics College were studied retrospectively. According to the extent of pelvic adhesions, tubal umbrella adhesions and atresia, 377 cases were classified into adhesion groups, including 73 cases in grade I, 221 cases in grade II, 75 cases in grade III and 8 cases in grade IV based on adhesion score. The 150 cases with no obvious pelvic adhesion were matched as control group. Among 8 cases with grade IV ahesion were exluded from ahesion group the relationship between pelvic adhesions and related history, abdominal lesions, tubal patency and the prognosis were studied. RESULTS: (1) Related factors: the frequency of pelvic adhesion and more than 7 years of infertility of 23.9% (88/369) in adhesion group were significantly higher than 12.0% (18/150) in control groups. (2) HISTORY: compared with the control group (12.7%, 19/150; 28.7%, 43/150; 11.3%, 17/150; 12.0%, 18/150; 17.3%, 26/150), patients with pelvic adhesions present more incidence abortion (23.6%, 87/369), uterine cavity operation (38.2%, 141/369), ectopic pregnancy (20.9%, 77/369), pelvic inflammatory disease (25.5%, 94/369) and abdominopelvic surgery (31.4%, 116/369). (3) Endoscopy exploration: the incidence of hydrosalpinx (24.7%, 91/369), tube distorted (15.7%, 58/369) and salpingostomy (72.9%, 269/369) in adhesion group were higher than those in control group (2.0%, 3/150; 4.0%, 6/150; 12.0%, 18/150), but relatively lower incidence of pelvic endometriosis lesions (5.7%, 21/369) and mesosalpinx cysts (16.3%, 60/369) than those in control group (16.0%, 24/150; 30.0%, 45/150). The rate of proximal tubal recanalization (59.5%, 91/153) in adhesion group was lower than 75.4% (52/69) in control group. However, the rate of distant tubal recanalization of 84.4%, (281/333) in adhesion group and; 13/15 in control group didn't show statistical difference. (4) PROGNOSIS: the rate of ectopic pregnancy of 9.7% (29/299) in adhesion group was significantly higher than 3.1% (4/128) in control group. Among cases with grade III adhesion exhibited the highest rate of ectopic pregnancy (13.0%, 7/54; OR = 4.62, 95%CI: 1.29 - 16.50). (5) Multivariate analysis: it was found that more than two drug abortions (OR = 3.29, 95%CI: 1.34 - 8.07), pelvic and(or) abdominal surgery history (OR = 2.20, 95%CI: 1.35 - 3.57) and pelvic inflammatory disease history (OR = 1.54, 95%CI: 1.21 - 1.97) were risk factors with pelvic adhesions. CONCLUSION: More than or equal to two drug abortion history, pelvic inflammatory disease and pelvic and abdominal surgery damage were important factors for pelvic adhesions of infertility patients, which may decrease the possibility of proximal tubal recanalization and increase ectopic pregnancy risk.

[The Chinese medicine syndrome features of ulcerative colitis by using fluorescence intensity of auto fluorescence imaging].

OBJECTIVE: To study the Chinese medicine (CM) syndrome features of ulcerative colitis (UC) by using fluorescence intensity (the ratio of green to red, G/R ratio) of auto fluorescence imaging, thus providing objective evidences for the CM syndrome typing of UC. METHODS: Totally 49 patients were recruited. They were typed as Dachang damp-heat syndrome (19 cases), Pi-Wei qi deficiency syndrome (30 cases), and the healthy control group (21 cases) on the bases of mucosal morphology of white light endoscopy (WLE) and the G/R ratio of AFI. RESULTS: Compared with the healthy control group (1.227 +/- 0.137), the G/R ratio in Dachang damp-heat syndrome (0.915 +/- 0.114) and Pi-Wei qi deficiency syndrome (1.147 +/- 0.137) decreased with statistical difference (P < 0.05, P < 0.01). Of them, it was lower in Dachang damp-heat syndrome group (P < 0.01). The case number was mainly dominated in moderate endoscopic index (EI) (11 cases) and severe EI (5 cases) in Dachang damp-heat syndrome group. The case number was mainly dominated in the remission phase (17 cases) and mild EI (7 cases) in Pi-Wei qi deficiency syndrome group. The G/R ratio of the remission phase was higher than that of the active phase (1.220 vs. 0.963, P < 0.01). There was statistical difference in the G/R ratio of the mild EI (1.044), the moderate EI (0.967), and the severe EI (0.830) (P < 0.01). CONCLUSIONS: The inflammation degree of Dachang damp-heat syndrome was more severe than that of Pi-Wei qi deficiency syndrome. AFI could better reflect the inflammation degree of UC.

Relationship between total testosterone, sex hormone-binding globulin levels and the severity of non-alcoholic fatty liver disease in males: a meta-analysis.

Background: In recent years, many studies have reported the relationship between non-alcoholic fatty liver disease (NAFLD) and sex hormones, especially total testosterone (TT) and sex hormone-binding globulin (SHBG). However, the relationship between sex hormones and the severity of NAFLD is still unclear. Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to 31 August 2021. Values of weighted mean differences (WMDs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the relationship between TT, SHBG and the severity of NAFLD in males. Results: A total of 2995 patients with NAFLD from 10 published cross-sectional studies were included for further analysis. The meta-analysis indicated that the moderate-severe group had a lower TT than the mild group in males with NAFLD (WMD: -0.35 ng/ml, 95% CI = -0.50 to -0.20). TT and SHBG were important risk factors of moderate-severe NAFLD in males (ORTT = 0.79, 95% CI = 0.73 to 0.86; ORSHBG = 0.22, 95% CI = 0.12 to 0.39; p < 0.001). Moreover, when the analysis was limited to men older than age 50, SHBG levels were lower in those with moderate-severe disease (WMD: -11.32 nmol/l, 95% CI = -14.23 to -8.40); while for men with body mass index (BMI) >27 kg/m2, moderate-severe NAFLD had higher SHBG levels than those with mild disease (WMD: 1.20 nmol/l, 95% CI = -2.01 to 4.42). Conclusion: The present meta-analysis shows that lower TT is associated with the severity of NAFLD in males, while the relationship between SHBG and severity of NAFLD is still to be further verified.

Application value of coaxial puncture needle (technique) in ultrasound-guided puncture biopsy of peripheral pulmonary masses.

This study aims to investigate the effect of ultrasound (US)-guided coaxial puncture needle in puncture biopsy of peripheral pulmonary masses. In this retrospective analysis, 157 patients who underwent US-guided percutaneous lung biopsy in our hospital were divided into a coaxial biopsy group and a conventional biopsy group (the control group) according to the puncture tools involved, with 73 and 84 patients, respectively. The average puncture time, number of sampling, sampling satisfaction rate, puncture success rate and complication rate between the 2 groups were compared and discussed in detail. One hundred fifty-seven patients underwent puncture biopsy, and 145 patients finally obtained definitive pathological results. The overall puncture success rate was 92.4% ([145/157]; with a puncture success rate of 97.3% [71/73] from the coaxial biopsy group and a puncture success rate of 88.1% [74/84] from the conventional biopsy group (P < .05). For peripheral pulmonary masses ≤3 cm, the average puncture time in the coaxial biopsy group was shorter than that in the conventional biopsy group, and the number of sampling, sampling satisfaction rate and puncture success rate were significantly higher than those in the conventional biopsy group (P < .05). There was no significant difference in the complication rate between the 2 groups (P > .05). For peripheral pulmonary masses >3 cm, the average puncture time in the coaxial biopsy group was still shorter than that in the conventional biopsy group (P < .05). The differences between the 2 groups in the number of sampling, satisfaction rate of the sampling, the success rate of puncture and the incidence of complications were not significant (P > .05). US guided coaxial puncture biopsy could save puncture time, increase the number of sampling, and improve the satisfaction rate of sampling and the success rate of puncture (especially for small lesions) by establishing a biopsy channel on the basis of the coaxial needle sheath. It provided reliable information for the diagnosis, differential diagnosis and individualized accurate treatment of lesions as well.

Prenatal exposure to koumine results in cognitive deficits and increased anxiety-like behavior in mice offspring.

Koumine (KM) is a major alkaloid monomer in the traditional Chinese medicine herb Gelsemium elegans Benth that has exhibited therapeutic potential in clinical applications. However, the pharmacological toxicological mechanism of this drug has not been fully explored. The purpose of this study was to evaluate the impacts of KM administration at a therapeutic dose in offspring. On gestational day 0, mice were injected with KM once daily for 4 consecutive days. Male and female offspring were subjected to behavioral tests and neuropathological analyses from postnatal day 60. Prenatal KM exposure resulted in cognitive and memory impairments in the Morris water maze, Y-maze test, and novel object recognition test. The open field test and elevated plus maze test indicated that prenatal KM exposure induced anxiety-like behavior in offspring. Electrophysiological experiments demonstrated that KM exposure inhibited hippocampal long-term potentiation. Immunostaining for neurogenesis markers DCX and BrdU demonstrated that KM suppressed adult neurogenesis in the subgranular zone of the dentate gyrus. In addition, prenatal KM exposure induced a significant reduction in dendritic spine density in hippocampal neurons. Synaptic formation-related proteins were decreased in the KM group based on western blot. No sex differences in the effects of KM were observed. Collectively, our results indicate that prenatal KA exposure has detrimental neural effects on offspring. This study provides a preliminary preclinical toxicological assessment of the safety of KM use during pregnancy.

Psychological Profiles of Chinese Patients With Hemodialysis During the Panic of Coronavirus Disease 2019.

Background: Hemodialysis patients not only suffer from somatic disorders but are also at high risks of psychiatric problems. Early this year, the outbreak of coronavirus disease 2019 (COVID-19) has caused great panic and anxiety worldwide. The impact of this acute public health event on the psychological status of hemodialysis patients and its relationship with their quality of life have not been fully investigated. Methods: This study comprised two parts. The initial study enrolled maintenance hemodialysis patients treated in Ruijin Hospital for more than 3 months from March to May 2020 during the ongoing COVID-19 pandemic. Patients completed three questionnaires including the Impact of Events Scale-Revised (IES-R), General Health Questionnaire-28 (GHQ-28), and Kidney Disease Quality of Life (KDQOL) Short Form (SF). Follow-up study was performed from December 2020 to January 2021, when the pandemic of COVID-19 has been effectively contained in China. Only patients enrolled in the initial study were approached to participate in the follow-up study. Results: There were 273 maintenance dialysis patients enrolled in the initial study and 247 finished the follow-up study. For the initial study, the estimated prevalence of nonspecific psychiatric morbidity was 45.8% (125/273) by GHQ-28. By IES-R, 53/273 (19.4%) patients presented with total scores above 24 that reflected clinical concerns. We found a significant difference regarding KDQOL scores between patients with different stress response (IES-R) groups (p = 0.026). Our follow-up study showed that KDQOL and SF-36 scores were significantly improved in comparison with those in the initial study (p = 0.006 and p = 0.031, respectively). Though total scores of GHQ-28 and IES-R did not change significantly, some subscales improved with statistical significance. Furthermore, gender, education background, and duration of hemodialysis were three factors that may affect patients' mental health, quality of life, or health status while dialysis duration was the only variable that correlated with those parameters. However, these correlations were combined effects of the COVID-19 pandemic and the dialysis itself. Conclusions: We found a correlation between changes in the mental health status of dialysis patients and changes in their quality of life. These responses were also mediated by patients' psychosocial parameters. Our results urge the necessity of psychotherapeutic interventions for some patients during this event.

A novel possible strategy based on self-assembly approach to achieve complete periodontal regeneration.

Limitations of current regeneration modalities underscore the importance of restoring the three-dimensional (3D) microenvironment of periodontal development, which is able to elicit the intrinsic capacity of mesenchymal stem cells to proceed to engage in a redevelopment-like program. With increased attention for the potential therapeutic applications of periodontal ligament stem cells (PDLSCs) in periodontal regeneration, it has been proposed that bone marrow mesenchymal stem cells (BMMSCs) are very likely another cell source of physiological repair of periodontal tissues. With this in mind, enlightened from the research targeting the fabrication of laminar structures such as liver and kidney with heterotypic stratification of cell sheets, we proposed a novel possible strategy based on self-assembly approach, which is akin to the physiological phenomenon that occurs during organogenesis, to enhance complete reconstruction of functional complex periodontium-organ systems. We assumed that in this strategy, using the intrinsic capacity of monodispersed cells to self-assemble into a microtissue such as a 3D spheroid, bilayered cell pellet constructs comprising calcified bone-forming cell pellets (i.e., BMMSCs) and cementum/PDL-forming cell pellets (i.e., PDLSCs) would be fabricated in vitro in a tissue-mimicking way and then implanted into periodontal defects. We hypothesize that this novel strategy might open new options to reconstruct extended periodontal defects and then achieve the ultimate goal of predictable and complete regeneration of the periodontium.

Role of long non-coding RNA MALAT1 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a pathological inflammatory condition of the lungs that is associated with high rates of mortality. Although long non-coding RNAs (lncRNAs) serve a role in lung diseases, their functions in COPD pathogenesis are relatively unknown. The present study aimed to assess the role of differentially expressed lncRNAs in COPD. Expression profile analysis of six lncRNAs in age-matched COPD and non-COPD tissues were conducted. Among the six tested lncRNAs, metastasis-associated in lung adenocarcinoma transcript 1 (MALAT1) was the most consistently overexpressed in COPD lung tissue specimens. To model COPD in vitro, human lung fibroblasts were treated with transforming growth factor-ß (TGF-ß) and MALAT1 was knocked down by small interfering RNA. This promoted cell viability and concurrently inhibited the expression of mesenchymal proteins, fibronectin and α-smooth muscle actin. In COPD, cell senescence is linked to the activation of mammalian target of rapamycin complex 1 (mTORC1). Upon gene silencing of MALAT1 in non-TGF-ß-treated cells, cells demonstrated constitutive activation of mTORC1, which was assessed by the protein expression levels of mTORC1 substrate S6 kinase (S6K1). By contrast, upon MALAT1 silencing in the TGF-ß-treated cells, mTORC1 activation was not suppressed, despite the mesenchymal cell markers protein expression levels being downregulated. Thus, lncRNA MALAT1 may represent a potent biomarker in COPD patients and may act as a target for both diagnostic and therapeutic purposes.

Impact of Somatic Mutations in Non-Small-Cell Lung Cancer: A Retrospective Study of a Chinese Cohort.

BACKGROUND: Somatic mutations are important biomarkers for selecting an optimal targeted therapy and predicting outcomes for non-small-cell lung cancer (NSCLC) patients that are often detected from tissue samples. However, tissue samples are not always readily available from these patients. The exploration of using circulating tumor DNA (ctDNA) to identify somatic mutations offers an alternative source that should be explored. METHODS: In this retrospective study, we included 280 patients diagnosed with adenocarcinoma between 2017 and 2018 in a hospital in eastern China. Tissue or ctDNA was collected, and a wide spectrum of somatic mutations was analyzed by targeted next-generation sequencing platforms. Associations among the mutation status, biomarkers, screening methods, disease stages, and interaction with treatment with overall survival (OS) were investigated. RESULTS: We found that the EGFR L858R mutation was the most frequently identified mutation in adenocarcinoma in this population by both methods, followed by KRAS (p=3.7e-09), PIK3CA (p=5e-04), and HER2 mutations (p=6.3e-03). We observed that EGFR mutations were significantly mutually exclusive with KRAS, HER2, and MET. FGFR1 mutations were significantly more abundantly detected in the ctDNA group. We found an interaction effect between EGFR mutation and target therapies. The ability of the targeted therapy to improve OS in patients with a single EGFR mutation (HR=0.069, p=0.07) approached significance, but this was not the case for the patients with more than one EGFR mutation or without an EGFR mutation (HR=0.813, p=0.725). Furthermore, the effect of chemotherapy was more predominant in the EGFR group in comparison to the control group. CONCLUSION: These findings provide useful information on the distribution of somatic mutations via different screening methods and how this related to the optimal treatment selection in Chinese patients with NSCLC.

[Investigation of long-term outcome for lung cancer of patients with neoadjuvant chemotherapy].

OBJECTIVE: To evaluate and analyze prognostic factors for surgical treatment of patients with neoadjuvant chemotherapy. METHODS: Records of 256 patients who underwent operation after chemotherapy for lung cancer from June 1995 to May 2007 were reviewed retrospectively. Potential prognostic factors which were univariately and multivariately analyzed by COX proportional hazard regression model, included gender, age, p-TNM stage, size of tumor, metastasis of lymph node, histological type and operation extent. Kaplan-Meier method was used for survival curve and rate. However, survival difference was calculate by Log-rank test. RESULTS: Eleven patients (4.3%) developed postoperative complications. Two hundred and thirty-six patients (92.2%) underwent radical resection (169 for lobectomies, 53 for pneumonectomies and 14 for extended resections). On the contrary, 20 cases had palliative resection. The overall 1-, 3- and 5-year survival rate was 79.3%, 38.7% and 27.0% respectively. Age, p-TNM stage, size of tumor, metastasis of lymph node and type of operation were valued as prognostic factors in COX univariate analysis, p-TNM stage (OR = 1.323, 95% CI: 1.068 to 1.641, P = 0.017) and age (OR = 1.562, 95% CI: 1.148 to 2.125, P = 0.005) were identified independent prognostic factors in COX multivariate analysis. CONCLUSIONS: Long-term outcome for lung cancer of patients with neoadjuvant chemotherapy are encouraging, p-TNM stage and surgical type are the crucial prognostic factors for surgical treatment of patients with neoadjuvant chemotherapy.

[Increased postprocedural neutrophil count is an independent predictive factor of poor prognosis in acute ST elevation myocardial infarction patients treated with percutaneous coronary intervention].

OBJECTIVE: The aim of the study was to evaluate the prognostic value of the postprocedural neutrophil count in patients with first acute ST elevation myocardial infarction (STEMI) treated with successful primary percutaneous coronary intervention (PCI). METHODS: A total of 226 consecutive STEMI patients underwent successful primary PCI were enrolled. Electrocardiograms were recorded before PCI and 2 hours after PCI. Neutrophil counts were measured within 12 hours after PCI. All patients were followed up for 2 years. Logistic regression analysis was used to evaluate predictive values of postprocedural neutrophil for ST-segment resolution (STR) after PCI and for death, non-fatal myocardial infarction and heart failure at 30 days and 2 years post PCI. Time-to-event analyses were performed using the Kaplan-Meier survival curves in patients with various ranges of postprocedural neutrophil counts. RESULTS: Postprocedural neutrophil count ranged from 2.83x10(9)/L to 18.74x10(9)/L, first quartile, median and fourth quartile were 5.66x10(9)/L, 7.38x10(9)/L and 9.34x10(9)/L respectively. Multivariable logistic analysis showed that when postprocedural neutrophil count increased 1x10(9)/L, the risk of non-STR increased 2.28 fold (OR: 2.28, P=0.009), the risk of death (OR: 1.63, P=0.010) and heart failure (OR: 1.16, P=0.035) at 30 days increased 1.63 and 1.16 folds respectively, and the risk of death (OR: 1.29, P=0.003) and heart failure (OR: 1.20, P=0.007) at 2 years increased 1.29 and 1.20 folds respectively, but the risk of non-fatal myocardial infarction was not affected by postprocedural neutrophil count. Furthermore, the patients with postprocedural neutrophil count>or=9.34x10(9)/L had significant lower 30-day (89.1% vs. 99.1% vs. 98.2%, P=0.010) and 2-year (82.4% vs. 96.1% vs. 96.3%, P=0.003) survival rates compared with the patients with postprocedural neutrophil count from 5.66x10(9)/L to 9.33x10(9)/L and the patients with postprocedural neutrophil count<5.66x10(9)/L (all P<0.05). CONCLUSION: Postprocedural neutrophil count is an independent predictor of short- and long-term death and heart failure in first acute STEMI patients treated with successful primary PCI.