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BACKGROUND: The demand for telesurgery is rapidly increasing. Augmented reality (AR) remote surgery is a promising alternative, fulfilling a worldwide need in fracture surgery. However, previous AR endoscopic and Google Glass remotes remain unsuitable for fracture surgery, and the application of remote fracture surgery has not been reported. The authors aimed to evaluate the safety and clinical effectiveness of a new AR remote in fracture surgery. MATERIALS AND METHODS: This retrospective non-inferiority cohort study was conducted at three centres. Between 1 January 2018 and 31 March 2022, 800 patients who underwent fracture surgery were eligible for participation. The study enroled 551 patients with fractures (132 patellae, 128 elbows, 126 tibial plateaus, and 165 ankles) divided into an AR group (specialists used AR to remotely guide junior doctors to perform surgeries) and a traditional non-remote group (specialists performed the surgery themselves). RESULTS: Among 364 patients (182 per group) matched by propensity score, seven (3.8%) in the AR group and six (3%) in the non-remote group developed complications. The 0.005 risk difference (95% CI: -0.033 to 0.044) was below the pre-defined non-inferiority margin of a 10% absolute increase. A similar distribution in the individual components of all complications was found between the groups. Hierarchical analysis following propensity score matching revealed no statistical difference between the two groups regarding functional results at 1-year follow-up, operative time, amount of bleeding, number of fluoroscopies, and injury surgery interval. A Likert scale questionnaire showed positive results (median scores: 4-5) for safety, efficiency, and education. CONCLUSION: This study is the first to report that AR remote surgery can be as safe and effective as that performed by a specialist in person for fracture surgery, even without the physical presence of a specialist, and is associated with improving the skills and increasing the confidence of junior surgeons. This technique is promising for remote fracture surgery and other open surgeries, offering a new strategy to address inadequate medical care in remote areas.

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Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

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BACKGROUND: Magnesium (Mg) is both an essential macro-element and a known catalyst, and it plays a vital role in various physiological activities and mechanisms in relation to chronic kidney disease (CKD). However, epidemiological evidence involving this is limited and not entirely consistent. This study aims to explore the association of serum Mg concentrations with the risk of CKD among general Chinese adults. METHODS: A total of 8,277 Chinese adults were included in the wave of 2009 from the China Health and Nutrition Survey (CHNS). The primary outcome was the risk of CKD, which was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multivariable logistic regression model was used to examine the relationship of serum Mg concentrations with the risk of CKD. RESULTS: Included were 8,277 individuals, with an overall CKD prevalence of 11.8% (n = 977). Compared with the first quartile of serum Mg, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for participants in the second, third, and fourth quartiles of serum Mg were 0.74 (0.58, 0.93), 0.87 (0.69, 1.11) and 1.29 (1.03, 1.61), respectively. Similar results were observed in our several sensitivity analyses. Restricted cubic spline analysis demonstrated a nonlinear (similar "J"-shaped) association between serum Mg concentrations and the risk of CKD (Pnonlinearity <0.001), with a threshold at around a serum Mg value of 2.2 mg/dL. CONCLUSIONS: Our results suggested a similar "J"-shaped association between serum Mg concentration and the risk of CKD among Chinese adults. Further large prospective studies are needed to verify these findings.

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Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 µg/m3 increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.

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Fungi are considered among the most efficient microbial degraders of plastics, as they produce salient enzymes and can survive on recalcitrant compounds with limited nutrients. In recent years, studies have reported numerous species of fungi that can degrade different types of plastics, yet there remain many gaps in our understanding of the processes involved in biodegradation. In addition, many unknowns need to be resolved regarding the fungal enzymes responsible for plastic fragmentation and the regulatory mechanisms which fungi use to hydrolyse, assimilate and mineralize synthetic plastics. This review aims to detail the main methods used in plastic hydrolysis by fungi, key enzymatic and molecular mechanisms, chemical agents that enhance the enzymatic breakdown of plastics, and viable industrial applications. Considering that polymers such as lignin, bioplastics, phenolics, and other petroleum-based compounds exhibit closely related characteristics in terms of hydrophobicity and structure, and are degraded by similar fungal enzymes as plastics, we have reasoned that genes that have been reported to regulate the biodegradation of these compounds or their homologs could equally be involved in the regulation of plastic degrading enzymes in fungi. Thus, this review highlights and provides insight into some of the most likely regulatory mechanisms by which fungi degrade plastics, target enzymes, genes, and transcription factors involved in the process, as well as key limitations to industrial upscaling of plastic biodegradation and biological approaches that can be employed to overcome these challenges.

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While exogenous metal/metalloid (metal) exposure has been associated with reduced human semen quality, no study has assessed the associations of exogenous metals in human spermatozoa with semen quality. Here, we developed a strategy to explore the associations between exogenous metals in spermatozoa at single-cell resolution and human semen quality among 84 men screened as sperm donors, who provided 266 semen samples within 90 days. A cellular atlas of exogenous metals at the single-cell level was created with mass cytometry (CyTOF) technology, which concurrently displayed 18 metals in more than 50 000 single sperm. Exogenous metals in spermatozoa at single-cell resolution were extremely heterogeneous and diverse. Further analysis using multivariable linear regression and linear mixed-effects models revealed that the heterogeneity and prevalence of the exogenous metals at single-cell resolution were associated with semen quality. The heterogeneity of lead (Pb), tin (Sn), yttrium (Y), and zirconium (Zr) was negatively associated with sperm concentration and count, while their prevalence showed positive associations. These findings revealed that the heterogeneous properties of exogenous metals in spermatozoa were associated with human semen quality, highlighting the importance of assessing exogenous metals in spermatozoa at single-cell resolution to evaluate male reproductive health risk precisely.

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Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.

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BACKGROUND: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. OBJECTIVE: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. METHODS: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility. RESULTS: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. CONCLUSION: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction.

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Cell phone use and radio-frequency electromagnetic radiation (RF-EMF) are rapidly increasing and may be associated with lower semen quality, yet results from epidemiological studies are inconclusive. Information on electronic devices use was collected through standard questionnaires from 1454 men aged 22-45 years old. Semen volume, sperm concentration, total sperm count, total motility, progressive motility, and normal morphology in repeated specimens were determined by trained clinical technicians. Percent changes [95% confidence intervals (CIs)] were estimated as (10ß-1) × 100 for electronic devices use associated with repeated sperm quality parameters in the linear mixed-effect models. After adjusting for multiple confounders, we found significant inverse associations of total duration of electronic devices use with sperm progressive motility and total motility, duration of cell phone and computer use with sperm concentration, progressive motility, and total motility (all P < 0.05). No significant association was found between cell phone/computer use alone and sperm quality parameters. Moreover, per hour increase of time spent on cell phone talking was associated with decreased sperm concentration and total count by an average of -8.0% (95% CI: -15.2%, -0.2%) and -12.7% (95% CI: -21.3%, -3.1%), respectively. Besides, daily calling time was associated with lower sperm progressive motility and total motility among those who used headsets during a call (P for interaction <0.05). In conclusion, our study suggested that more time spent on electronic devices use had a modest reduction effect on semen quality. Daily calling time was significantly associated with lower sperm concentration and total count, and using headsets during a call appeared to aggravate the negative association between daily calling time and sperm motility. Additional studies are needed to confirm these findings.

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Information on the association between tea drinking and semen quality is limited. Little is reported on whether tea drinking is benefit to sperm quality. This cross-sectional and longitudinal study was conducted between April 2017 and July 2018. Participants were healthy men who were screened as potential sperm donors recruited at the Hubei Province Human Sperm Bank of China. A structured questionnaires containing sociodemographic information, daily habits, sperm collection-related information was completed for each participant at interview. Repeated semen samples were taken to examine the sperm parameters, including sperm volume, sperm concentration, sperm count, progressive motility, and total motility. A total of 1385 men with 6466 sperm samples were included in this study. Two groups were compared: tea drinking men (389, 28.1%) and non-tea drinking men (996, 71.9%). Compared with subjects who never drink tea, the analyses showed that sperm concentration and total sperm count were higher in tea-consuming subjects. A 10-year period or more duration of tea drinking significantly increased semen concentrations by 16.27% (P < 0.05). Sperm concentration was increased in subjects with a frequency of tea drinking of 3 days or more per week (P < 0.05) or, among men who were occasional alcohol drinkers, when tea concentration was weak (P < 0.05). No evidence of trend effects (P for trend > 0.05) or interaction effects (P for interaction > 0.05) between tea consumption and sperm quality, respectively. Our findings provide evidence that tea drinking may improve male reproductive health. Long-term, frequent, weak tea drinking tends to increase sperm quality among men with low BMI or health-related behaviors like smoking or alcohol intake.

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Accumulating epidemiological evidence shows that handgrip strength provides predictive potential in physical, mental, and reproductive health status. However, the associations between handgrip strength and semen characteristics have not been explored. We recruited 1382 eligible men at the Hubei Province Human Sperm Bank (Wuhan, China) who had their handgrip strength measured at recruitment and provided 6458 repeated semen specimens within a 6-month period. Semen characteristics, including semen volume, sperm motility parameters (immotility, nonprogressive motility, and progressive motility), and sperm concentration, were assessed. Mixed-effect models and restricted cubic spline functions were applied to investigate the relationship of handgrip strength with repeated measurements of semen characteristics. After adjusting for confounding factors, the mixed-effect models revealed that handgrip strength was positively associated with semen volume, sperm concentration, progressive motility, total motility, and total count (all P for trend < 0.05). Compared to men in the lowest quartile, those in the highest quartile of handgrip strength had higher semen volume, sperm concentration, progressive motility, total motility, and total count, with measurements of 14.2% (95% confidence interval [CI]: 5.9%-23.2%), 19.5% (95% CI: 7.3%‒33.1%), 9.5% (95% CI: 3.4%‒15.9%), 8.8% (95% CI: 3.2%‒14.6%), and 36.4% (95% CI: 18.9%‒56.5%), respectively. These positive dose-response relationships were further confirmed in restricted cubic splines, where handgrip strength was modeled as a continuous variable. Handgrip strength, as an indicator of muscular function and strength, was positively associated with semen characteristics in a dose-dependent manner.

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OBJECTIVE: To investigate the association between mitochondrial DNA copy number (mtDNAcn) and semen quality. DESIGN: A cross-sectional study. SETTING: Hubei Province Human Sperm Bank of China (from April 2017 to July 2018). POPULATION: A total of 1164 healthy male sperm donors with 5739 specimens. MAIN OUTCOME MEASURES: Real-time quantitative polymerase chain reaction (RT-PCR) was used to measure sperm mtDNAcn. We also determined semen volume, concentration and motility parameters (progressive motility, nonprogressive motility and immotility). METHODS: Mixed-effect models and general linear models were uses. RESULTS: After adjusting for relevant confounding factors, mixed-effect models revealed diminished sperm motility (progressive and total), concentration, and total count across the quartiles of mtDNAcn (all P < 0.05). Compared with men in the lowest quartile, men in the highest quartile of mtDNAcn had lower progressive sperm motility, total motility, concentration and total count of -8.9% (95% CI -12.7% to -5.0%), -8.0% (95% CI -11.6% to -4.4%), -42.8% (95% CI -47.7% to -37.4%), and - 44.3% (95% CI -50.1% to -37.7%), respectively. These inverse dose-response relationships were further confirmed in the cubic spline models, where mtDNAcn was modelled as a continuous variable. CONCLUSIONS: We found that mtDNAcn was inversely associated with semen quality in a dose-dependent manner. Our results provide novel clues that sperm mtDNAcn may serve as a useful predictor of human semen characteristics. TWEETABLE ABSTRACT: Sperm mitochondrial DNA copy number was markedly associated with diminished sperm motility (progressive and total), concentration and total count.

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OBJECTIVE: To explore the association between depression and semen quality and the mediating role of oxidative stress. DESIGN: Cross-sectional study with repeated measures of semen quality. SETTING: Human Sperm Bank of Hubei Province, People's Republic of China. PATIENT(S): From April 2017 to July 2018, we recruited 1,000 potential sperm donors who completed the Beck Depression Inventory questionnaire and had measures of oxidative stress biomarkers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Severity of depression was evaluated by the Beck Depression Inventory scores (0-4, no depression; 5-13, mild depression; 14-20, moderate depression; and 21 or greater, severe depression). The urinary concentrations of 8-hydroxy-2-deoxyguanosine, 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α (8-isoPGF2α) were measured to reflect oxidative stress status. Repeated semen quality parameters (n = 5,880) were examined by trained professional technicians according to the World Health Organization laboratory manual. Associations between depression, oxidative stress, and repeated measures of semen quality parameters were evaluated using linear or mixed-effects models with adjustment for potential confounders. Mediation analysis was performed to test the potential mediating role of oxidative stress. RESULT(S): A total of 391 (39.1%) men were classified as mild depression, 67 (6.7%) as moderate depression, and 19 (1.9%) as severe depression. Inverse dose-response relationships between severity of depression and semen quality parameters were found. Compared with men without depression (n = 523), those with severe depression had a 25.26% (95% confidence interval, -38.65%, -8.93%) lower semen volume, 37.04% (-55.37%, -11.20%) lower total sperm count, 13.57% (-23.17%, -2.78%) lower total motility, and 15.08% (-25.09%, -3.72%) lower progressive motility; men with moderate depression also had a 12.28% (-21.16%, -2.40%) lower semen volume and 23.56% (-36.50%, -7.97%) lower total sperm count. We found a positive dose-response relationship between severity of depression and urinary 8-isoPGF2α concentrations. However, we found no evidence that the associations between depression status and semen quality were mediated by oxidative stress markers. CONCLUSION(S): In the study of Chinese male sperm donors, men with depression had worse semen quality parameters, including semen volume, sperm concentration, total sperm count, total motility, and progressive motility. Although depression was positively associated with urinary 8-isoPGF2α concentrations, depression-semen quality associations were not mediated by oxidative stress.

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The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL-1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL-1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1ß, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

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BACKGROUND: Essential elements such as iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), and molybdenum (Mo) are necessary for reproductive health. However, their associations with human semen quality remain inconclusive. OBJECTIVES: To investigate the associations of urinary Fe, Co, Cu, Zn, Se, Rb, Sr, and Mo concentrations with semen quality in healthy men screened as potential sperm donors and identify critical windows of susceptibility. METHODS: 1428 healthy men provided 3766 urine and 6527 semen samples, which were measured for urinary essential element concentrations and sperm quality parameters, respectively. Linear mixed models and cubic spline curves were used to evaluate associations between urinary essential elements and semen quality. Multiple informant models were used to identify potential critical windows of susceptibility. RESULTS: Linear mixed models and cubic spline curves showed positive dose-response relationships between urinary Zn and sperm concentration and total count and between urinary Mo and total sperm count [all False Discovery Rate (FDR) adjusted p-value for trend < 0.05]. In the multiple-element linear mixed models, the men in the highest versus lowest quartiles of urinary Zn and Mo had a higher sperm concentration of 17.5% (95% CI: 2.8%, 34.2%; p-value for trend = 0.006) and total sperm count of 18.3% (95% CI: 1.4%, 38.0%; p-value for trend = 0.027), respectively. Urinary Zn was also positively associated with total sperm count in a dose-dependent manner (p-value for trend = 0.036), though the percentile difference in total sperm count between men in the highest and lowest quartile was not statistically significant (16.4%, 95% CI: -1.7%, 37.9%). These associations appeared to be stronger when urinary Zn and Mo were measured at 0-9 days before the date of semen examination (i.e., corresponding to epididymal storage). CONCLUSIONS: Higher urinary Zn and Mo, particularly during the period of epididymal storage, were associated with greater sperm production.

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A single measurement of organophosphate flame retardant (OPFR) metabolites in a spot sample is often used in epidemiological studies to estimate individual exposures. Over seven consecutive days, we collected 661 spot samples, including 127 first morning voids (FMVs) and 123 simulated 24-h collections, from 20 healthy adults and analyzed for eight OPFR metabolites. Intraclass correlation coefficients (ICCs) were calculated to evaluate the variability of the analyzed metabolites. In spot samples group, serial measurements of OPFR metabolites showed poor reproducibility (0.0422 ≤ ICC ≤ 0.349), and the within-day variability was the main contributor of the total variability. The estimated ICCs based on different correction methods for urine dilution (i.e., specific gravity-adjusted, creatinine-adjusted, and creatinine as a covariate) were similar, but varied according to gender and body mass index. Uniformly low sensitivities (0.417-0.633) were observed when using a single FMV or spot sample to predict the 1-week highly (top 33.0%) exposed volunteers. Therefore, using a single urinary measurement to predict chronic exposure to OPFRs can lead to a high degree of classification errors. When multiple urine samples are collected, considering the sampling type, the time of collection, and demographic characteristics may provide a more complete approach to assess exposure to diverse OPFRs.

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BACKGROUND: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. METHODS: We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9·5 109/L) or lymphopenia (<1·1 109/L). FINDINGS: Normal or decreased number of leukocytes (≤9·5 109/L), lymphopenia (<1·1 109/L), eosinopenia (<0·02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95·0%, 52·2%, 74·7% and 86·7% of COVID-19 patients, much higher than 87·2%, 28·8%, 31·3% and 45·2% of the controls, respectively. The eosinopenia produced a sensitivity of 74·7% and specificity of 68·7% for separating the two groups with the area under the curve (AUC) of 0·717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67·9% and specificity of 78·2% (AUC=0·730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). INTERPRETATION: The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination.

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PURPOSE: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

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BACKGROUND: Trihalomethanes (THMs) have demonstrated adverse effects on male reproductive systems in experimental animals, but human evidence has been inconsistent. Prior researches have been limited by small sample sizes and inadequate exposure assessment. OBJECTIVES: To investigate the association between blood THMs and repeated measurements of semen quality parameters among 1199 healthy men screened as potential sperm donors. METHODS: We recruited healthy men presenting to the Hubei Province Human Sperm Bank from April to December 2017. At study entry, each participant provided a spot blood sample which was used to quantify blood concentrations of four THMs: chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM). The summary measures of exposure for brominated THMs (Br-THMs; molar sum of BDCM, DBCM and TBM) and total THMs (TTHMs; molar sum of TCM and Br-THMs) were also calculated. We used multivariable linear regression models to estimate the cross-sectional associations of tertiles of blood THM concentrations with semen quality parameters measured at study entry, and mixed-effect models to estimate the longitudinal associations accounting for repeated measures of semen quality, adjusting for relevant confounding factors. RESULTS: In the cross-sectional analysis, several inverse dose-response relationships were observed across tertiles of blood TCM concentrations and sperm count, total motility and progressive motility, and between blood DBCM, and Br-THMs, and TTHMs and sperm count and concentration. The inverse associations of blood TCM, DBCM, Br-THMs and TTHMs with sperm count were confirmed in the longitudinal, repeated measure analysis. CONCLUSION: Our results suggest that exposure to THMs from drinking water may be related to decreased semen quality in young healthy men.

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BACKGROUND: Short sleep duration and poor sleep quality are increasingly prevalent in modern society and may be associated with impaired semen quality, yet studies are inconclusive. OBJECTIVES: To investigate the reproducibility of semen quality parameters among 842 healthy men screened as potential sperm donors and explore the associations of sleep duration and quality with repeated measures of semen quality parameters. METHODS: We assessed sleep duration (night sleep and daytime napping) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) among 842 healthy men screen as potential sperm donors. We examined sleep characteristics in relation to repeated measurements (n = 5601) of semen parameters using linear mixed-effects models. RESULTS: High degrees of within-individual variability were found for total and progressive sperm motility with intraclass correlation coefficient (ICC) of 0.20 and 0.22, respectively; while fair-to-good reproducibilities were observed for sperm volume, concentration, and total count (ICC = 0.54, 0.62, and 0.50, respectively). Compared to men with total sleep duration of 8.0-8.5 h/day (h/d), men who slept less than 6.0 h/d and higher than 9.0 h/d had lower sperm volume of 12% [95% confidence interval (CI): -22%, -0.68%] and 3.9% (95% CI: -7.3%, -0.44%), respectively. Compared to men with night sleep duration of 7.5-8.0 h/d, men who slept less than 6.0 h/d had lower total and progressive sperm motility of 4.4% (95 CI:-8.4%, -0.24%) and 5.0% (95% CI: -9.2%, -0.48%), respectively. Compared to men who reported good sleep quality (total PSQI score ≤5.0), those reporting poor sleep quality (total PSQI score >5.0) had lower total sperm count, total motility, and progressive motility of 8.0% (95% CI: -15%, -0.046%), 3.9% (95% CI: -6.2%, -1.5%), and 4.0% (95% CI: -6.5%, -1.4%), respectively. CONCLUSIONS: Both long and short sleep duration and poor sleep quality were associated with impaired semen quality parameters. The high within-individual variability of total and progressive sperm motility suggests that a single measurement may result in a moderate degree of classification error.

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