Selective Inhibition of hsp90 Paralogs: Uncovering the Role of Helix 1 in Grp94-Selective Ligand Binding.

Grp94 is the endoplasmic reticulum paralog of the hsp90 family of chaperones, which have been targeted for therapeutic intervention via their highly conserved ATP binding sites. The design of paralog-selective inhibitors relies on understanding the protein structural elements that drive higher affinity in selective inhibitors. Here, we determined the structures of Grp94 and Hsp90 in complex with the Grp94-selective inhibitor PU-H36, and of Grp94 with the non-selective inhibitor PU-H71. In Grp94, PU-H36 derives its higher affinity by utilizing Site 2, a Grp94-specific side pocket adjoining the ATP binding cavity, but in Hsp90 PU-H36 occupies Site 1, a side pocket that is accessible in all paralogs with which it makes lower affinity interactions. The structure of Grp94 in complex with PU-H71 shows only Site 1 binding. While changes in the conformation of helices 4 and 5 in the N-terminal domain occur when ligands bind to Site 1 of both Hsp90 and Grp94, large conformational shifts that also involve helix 1 are associated with the engagement of the Site 2 pocket in Grp94 only. Site 2 in Hsp90 is blocked and its helix 1 conformation is insensitive to ligand binding. To understand the role of helix 1 in ligand selectivity, we tested the binding of PU-H36 and other Grp94-selective ligands to chimeric Grp94/Hsp90 constructs. These studies show that helix 1 is the major determinant of selectivity for Site 2 targeted ligands and also influences the rate of ATPase activity in Hsp90 paralogs.

A novel strategy for predicting the efficacy of temozolomide treatment for metastatic pheochromocytomas/paragangliomas.

BACKGROUND: There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment. METHODS: This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment. RESULTS: 62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ. CONCLUSIONS: This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application.

[Clinical analysis of robotic-assisted surgery in the treatment of large pheochromocytoma/paraganglioma: a study of 29 cases].

This study aimed to compare the safety and clinical efficacy of Da Vinci robotic surgery (control group) versus traditional laparoscopic surgery in the treatment of large (tumor size >6 cm) pheochromocytomas/paragangliomas. The evaluation was based on intraoperative metrics such as operative time, blood loss, conversion to open surgery rates, postoperative drain duration, and length of postoperative hospital stay. A retrospective analysis was conducted on 29 patients (14 males and 15 females) who underwent Da Vinci robotic surgery for large (greater than 6 cm) pheochromocytomas/paragangliomas from October 2019 to September 2023. The average maximum tumor diameter was (7.2±1.6) cm. During the same period, 32 patients underwent laparoscopic resection of challenging pheochromocytomas/paragangliomas.Data showed no significant differences between the two groups, except for the norepinephrine levels. Operative time, blood loss, conversion rate, postoperative drainage duration, and length of hospital stay were recorded and compared between the two groups. The differences between the groups were analyzed using the t-test, and the conversion rates were compared using the chi-square (χ²) test. All surgeries were successfully performed. One patient underwent a one-stage bilateral tumor resection. In the Da Vinci robotic surgery group, the average operative time was (76±32) minutes, compared to (106±45) minutes in the control group (P=0.003). The average intraoperative blood loss was (95±75) ml, compared to (160±90) ml in the control group (P=0.019). The conversion rate to open surgery was 2 cases (6.9%) in the robotic group compared to 5 cases (15.6%) in the control group (P=0.031). The average postoperative drainage duration was (3.0±1.0) days, compared to (3.5±1.5) days in the control group (P=0.128). The average length of hospital stay was (4.5±1.2) days, compared to (4.7±2.2) days in the control group (P=0.657). Postoperative pathological diagnosis confirmed pheochromocytoma or paraganglioma. Blood pressure normalized within 1 to 3 months postoperatively, with an average systolic blood pressure of (116±13) mmHg(1 mmHg=0.133 kPa）and diastolic blood pressure of (73±5) mmHg in the robotic surgery group. Follow-up for 3 to 40 months showed normal levels of blood catecholamines and no recurrence or metastasis on follow-up imaging studies, including chest, abdominal, and pelvic CT scans. The average levels of 3-methoxy-norepinephrine, 3-methoxy-epinephrine, and 3-methoxy-tyramine were (0.42±0.21) nmol/L (normal value≤1.05 nmol/L), (0.11±0.07) nmol/L (normal value≤0.32 nmol/L), and (0.017±0.006) nmol/L (normal value≤0.036 nmol/L), respectively. This study demonstrates that for the treatment of large pheochromocytomas/paragangliomas, the Da Vinci robotic technique offers advantages such as high-definition visualization, precise operation, and flexibility. These advantages enable the safe and efficient completion of surgeries, as evidenced by shorter operative times, less blood loss, and lower conversion rates.

[Progress in the diagnose and treatment of pulmonary arterial thrombosis in situ].

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Genome-wide association study identifies variants associated with semen volume in white-feathered broilers.

Semen is a measure of the reproductive efficiency of roosters, which affects the economic benefits of white-feathered broilers. Over the years, research in this field has mainly focused on hens, while there have been fewer studies on the reproductive traits of roosters. To identify the genes related to the semen traits of roosters, we used a chicken 55 K SNP chip to genetically type the white-feathered population (220) and performed imputation with resequencing data from 97 roosters. In total, 1 048 576 SNPs were obtained and used for genome-wide association analysis of semen volume, from which 197 genome-wide significant markers were identified, all within the interval of 13.82-16.12 Mb on chromosome 7. By combining our results with the biological functions of genes in the interval, four candidate genes were identified that potentially relate to semen volume: FAPP1, OSBPL6, SESTD1 and SSFA2. Our findings may provide a basis for further research on the genetic mechanism and marker-assisted selection of semen volume in white-feathered broilers.

Exploring artificial intelligence from a clinical perspective: A comparison and application analysis of two facial age predictors trained on a large-scale Chinese cosmetic patient database.

BACKGROUND: Age prediction powered by artificial intelligence (AI) can be used as an objective technique to assess the cosmetic effect of rejuvenation surgery. Existing age-estimation models are trained on public datasets with the Caucasian race as the main reference, thus they are impractical for clinical application in Chinese patients. METHODS: To develop and select an age-estimation model appropriate for Chinese patients receiving rejuvenation treatment, we obtained a face database of 10 529 images from 1821 patients from the author's hospital and selected two representative age-estimation algorithms for the model training. The prediction accuracies and the interpretability of calculation logic of these two facial age predictors were compared and analyzed. RESULTS: The mean absolute error (MAE) of a traditional support vector machine-learning model was 10.185 years; the proportion of absolute error ≤6 years was 35.90% and 68.50% ≤12 years. The MAE of a deep-learning model based on the VGG-16 framework was 3.011 years; the proportion of absolute error ≤6 years was 90.20% and 100% ≤12 years. Compared with deep learning, traditional machine-learning models have clearer computational logic, which allows them to give clinicians more specific treatment recommendations. CONCLUSION: Experimental results show that deep-learning exceeds traditional machine learning in the prediction of Chinese cosmetic patients' age. Although traditional machine learning model has better interpretability than deep-learning model, deep-learning is more accurate for clinical quantitative evaluation. Knowing the decision-making logic behind the accurate prediction of deep-learning is crucial for deeper clinical application, and requires further exploration.

COVID-19 pandemic and neonatal birth weight: a systematic review and meta-analysis.

OBJECTIVES: Lockdown was implemented in many countries during the pandemic, which led to myriad changes in pregnant women's lives. However, the potential impacts of the COVID-19 pandemic on neonatal outcomes remain unclear. We aimed to evaluate the association between the pandemic and neonatal birth weight. STUDY DESIGN: This was a systematic review and meta-analysis of the previous literature. METHODS: We searched the MEDLINE and Embase databases up to May 2022 and extracted 36 eligible studies that compared neonatal birth weight between the pandemic and the prepandemic period. The following outcomes were included: mean birth weight, low birth weight (LBW), very low birth weight (VLBW), macrosomia, small for gestational age (SGA), very small for gestational age (VSGA), and large for gestational age (LGA). Statistical heterogeneity among studies was assessed to determine whether a random effects model or fixed effects model was conducted. RESULTS: Of the 4514 studies identified, 36 articles were eligible for inclusion. A total of 1,883,936 neonates during the pandemic and 4,667,133 neonates during the prepandemic were reported. We identified a significant increase in mean birth weight (pooled mean difference [95% confidence interval (CI)] = 15.06 [10.36, 19.76], I2 = 0.0%, 12 studies) and a reduction in VLBW (pooled OR [95% CI] = 0.86 [0.77, 0.97], I2 = 55.4%, 12 studies). No overall effect was identified for other outcomes: LBW, macrosomia, SGA, VSGA, and LGA. There was publication bias for mean birth weight with a borderline significance (Egger's P = 0.050). CONCLUSION: Pooled results showed the pandemic was significantly associated with an increase in mean birth weight and a reduction in VLBW, but not for other outcomes. This review provided clues about the indirect effects of the pandemic on neonatal birth weight and more healthcare measures needed to improve neonatal long-term health.

[Multivariable analysis of tooth loss in subjects with severe periodontitis over 4-year natural progression].

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION: In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.

[Application effects of 3D visualization reconstruction technique in pheochromocytoma/ paraganglioma surgery].

To investigate the value of 3D visualization reconstruction technology in pheochromocytoma/paraganglioma surgery.The clinical data of 87 patients with pheochromocytoma/paraganglioma admitted to the Department of Urology of Peking Union Medical College Hospital between January 2019 and December 2022 were retrospectively analyzed, and 3D visualization model reconstruction was performed preoperatively in 47 patients [Group A:males was 24 cases,the age M(Q1, Q3)42.00(30.00, 54.00)]. while the remaining 40 patients [Group B: males was 23 cases,the age M(Q1, Q3) 44.00(30.25, 53.75)] was not. The maximum tumor diameter, operation time, intraoperative bleeding, drain retention time and postoperative hospital stay were compared between the two groups. Surgery was successfully completed in both groups. 37 (78.7%) patients in group A underwent laparoscopic surgery, 7 (14.9%) patients underwent open surgery, and 3 (6.4%) patients underwent laparoscopic-to-open surgery. Thirty-one (77.5%) patients in group B underwent laparoscopic surgery, 5 (12.5%) patients underwent open surgery, and 4 (10.0%) patients underwent laparoscopic to open surgery. There was a difference in the maximum diameter of the tumor between the two groups [(6.09±3.02) cm vs (5.32±1.76) cm, P<0.05], the retention time of the drainage tube was significantly shorter in group A compared with group B [(3.20±1.38) d vs (4.02±1.98) d, P<0.05], and the length of the hospital stay after surgery was significantly shorter [(5.75±2.12) d vs (6.49±3.37) d, P<0.05]. Comparison of operation time and intraoperative bleeding between the two groups showed no statistically significant difference (P>0.05).Two cases of postoperative anemia and one case of pulmonary atelectasis in group B patients improved before discharge. Conclusion when the tumor diameter is>6 cm or has a close relationship with the surrounding organs and blood vessels, the use of 3D visual reconstruction technology can formulate and implement a more accurate and safe surgical plan, shorten the retention time of the drainage tube and postoperative hospitalization time, which is conducive to the patient's postoperative recovery and reduce postoperative complications.

[Influence of disposable diaper dependence on emotional behavior and related factors of preschool-aged children].

Objective: To investigate the influence of disposable diaper dependence (DDD) on emotional behavior and related factors of preschool-aged children. Methods: A total of 3 000 preschool-aged children from 16 kindergartens in Zhengzhou of Henan Province from October 2019 to March 2020 were selected and their parents were investigated by using a basic information questionnaire (including usage of disposable diapers), Strengths and Difficulties Questionnaire (SDQ) and Children's Sleep Questionnaire (PSQ). The differences in baseline and clinical data were compared between the DDD children and normal children, and multiple linear regression models were used to analyze the factors associated with emotional behavior in DDD children. Results: A total of 3 000 questionnaires were distributed and 2 775 (92.50%) were valid. The children ranged in age from 3 to 5 years, including 1 438 boys (51.82%) and 1 337 girls (48.18%). There were 98 (3.53%) children in DDD group and 2 677 (96.47%) children in normal group. The proportion of children living in cities in the DDD group was 58.16%, significantly higher than that of 41.84% in the normal children group (P<0.001). The abnormal detection rate of various factors in SDQ in DDD children, from high to low, were hyperactivity (n=14, 14.29%), peer communication problems (n=12, 12.24%), prosocial behavior (n=11, 11.22%), emotional symptoms (n=10, 10.20%) and conduct problems (n=7, 7.14%). The detection rates of abnormal total difficulty scores in DDD group and normal children were 7.14% (7 cases) and 0.78% (21 cases), respectively, with statistically significant differences (P<0.001). The proportions of emotional symptoms and hyperactivity disorder in DDD group were higher than those in normal group, and the differences were statistically significant (P<0.05). The PSQ score of children in DDD group was 3.01±2.02 which was not significantly different from the PSQ score of the normal group (2.71±2.10, P=0.157). The multi-factor analysis showed that caregiver's education level (ß=-1.135,95%CI:-1.910 to -0.359), urinary incontinence (ß=2.222, 95%CI: 1.105-3.339), fecal incontinence (ß=3.833, 95%CI: 2.691-4.975), urinary and fecal incontinence (ß=5.522, 95%CI: 4.145-6.899), and recurrent urinary tract infections(ß=3.523,95%CI: 1.798-5.248)were the independent influencing factors of emotional behavioral problems in DDD children (P<0.05). Conclusions: Children with DDD are more likely to have emotional behavioral problems than normal children. Caregiver's education level, urinary incontinence and recurrent urinary tract infections were influencing factors of emotional behavioral problems in DDD children.

Risk stratification for hepatocellular carcinoma of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) and the diagnostic performance of LR-5 and LR-M: a systematic review and meta-analysis.

AIM: To evaluate the risk stratification of hepatocellular carcinoma (HCC) and overall malignancies in different contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) categories, and to explore the diagnostic performance of LR-5 for HCC and LR-M for non-HCC malignancies. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Central databases were searched from 2016 to February 2021 for studies on CEUS LI-RADS v2016 and v2017. The proportion of HCC and overall malignancy in each LI-RADS category and the sensitivity, specificity, accuracy, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LR-5 and LR-M categories were determined using a random effects model. RESULTS: A total of 113 studies were retrieved and 10 studies were included. A total of 5,543 patients with 6,124 lesions were included, including 4,492 HCC. There was no HCC in LR-1, and the proportion of HCC in LR-2-5 increased with the increase of category. The proportion of HCC in LR-5 was 97%, and that in LR-M was 44%. The sensitivity, specificity, and accuracy of CEUS LR-5 for HCC were 0.76, 0.95, and 0.82, respectively, and the area under the SROC curve was 0.83. The sensitivity, specificity, and accuracy of CEUS LR-M for non-HCC malignancies were 0.81, 0.92, and 0.91, and the area under the SROC curve was 0.89. CONCLUSION: The risk of HCC increases gradually from LR-1 to LR-5, in which there was no HCC lesion in LR-1 and the proportion of HCC in LR-3 was 22%, lower than that reported in earlier studies. The proportion of HCC in LR-5 was 97% and that in LR-M was 44%. LR-5 has a high specificity of 95% for the diagnosis of HCC.

Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

WormBase: a modern Model Organism Information Resource.

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.

Impacts of COVID-19 pandemic on preterm birth: a systematic review and meta-analysis.

OBJECTIVES: The COVID-19 pandemic has significantly affected healthcare systems and daily well-being. However, the reports of the indirect impacts of the pandemic on preterm birth remain conflicting. We performed a meta-analysis to examine whether the pandemic altered the risk of preterm birth. STUDY DESIGN: This was a systematic review and meta-analysis of the previous literature. METHODS: We searched MEDLINE and Embase databases until March 2022 using appropriate keywords and extracted 63 eligible studies that compared preterm between the COVID-19 pandemic period and the prepandemic period. A random effects model was used to obtain the pooled odds of each outcome. The study protocol was registered with PROSPERO (No. CRD42022326717). RESULTS: The search identified 3827 studies, of which 63 reports were included. A total of 3,220,370 pregnancies during the COVID-19 pandemic period and 6,122,615 pregnancies during the prepandemic period were studied. Compared with the prepandemic period, we identified a significant decreased odds of preterm birth (PTB; <37 weeks' gestation; pooled odds ratio [OR; 95% confidence interval (CI)] = 0.96 [0.94, 0.98]; I2 = 78.7%; 62 studies) and extremely PTB (<28 weeks' gestation; pooled OR [95% CI] = 0.92 [0.87, 0.97]; I2 = 26.4%; 25 studies) during the pandemic, whereas there was only a borderline significant reduction in the odds of very PTB (<32 weeks' gestation; pooled OR [95% CI] = 0.93 [0.86, 1.01]; I2 = 90.1%; 33 studies) between the two periods. There was significant publication bias for PTB. CONCLUSION: Pooled results suggested the COVID-19 pandemic was associated with preterm birth, although there was only a borderline significant reduction for very PTB during the pandemic compared with the prepandemic period. Large studies showed conflicting results, and further research on whether the change is related to pandemic mitigation measures was warranted.

Combined effects of multi-land use decisions and climate change on water-related ecosystem services in Northeast China.

Land use intensification and climate change have resulted in substantial changes in the provision of ecosystem services, particularly in China that experienced sharp increases in population growth and demands for goods and energy. To protect the environment and restore the degraded ecosystems, the Chinese government has implemented multiple national ecological restoration projects. Yet, the combined effects of climate change and land use and land cover change (LULCC) over large spatial scales that brace multiple land use decisions and great environmental heterogeneity remain unclear. We assessed the combined effects of LULCC and climate change on water-related ecosystem services (water provision and soil conservation services) from 1990s to 2020s in Northeast China using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. We found that water yield decreased by 9.78% and soil retention increased by 30.51% over the past 30 years. LULCC and climate change exerted negative effects on water yield whereas they both enhanced soil retention; LULCC interacted with climate change to have relatively small inhibitory effects on water yield and large facilitation effects on soil retention. Changes in water yield were mainly attributed to climate change, while soil retention was largely influenced by LULCC and its interaction with climate change. Our research highlights the importance of land use decisions and its interactive effects with climate change on ecosystem services in a heavily disturbed temperate region, and provides important information to inform future land management and policy making for sustaining diverse ecosystem services and ensuring human wellbeing.

[Pay attention to lower urinary tract dysfunction and the clinical application of urodynamic studies in children].

Lower urinary tract dysfunction (LUTD) is the dysfunction of bladder and urethra during bladder filling and voiding phase. There are two general categories: neurogenic and non-neurogenic. It can cause upper urinary tract damage if left untreated. Urodynamic study (UDS) can objectively detect the function of detrusor and sphincter of urethra as well as predict the damage of LUTD to upper urinary tract. However, the development of UDS for children in China has not been popularized, which affects the accurate diagnosis and the treatment of LUTD. This article reviewed the importance of paying attention to LUTD and promoting the clinical application of UDS in children, so as to improve the diagnosis and treatment of LUTD in children.

[Risk factors of postoperative voiding dysfunction in children with congenital anorectal malformation].

This study analyzed the clinical data of children with anorectal malformation (ARM)who underwent surgery from 2006 to 2021, and explored the related factors of postoperative voiding dysfunction (VD).A total of 60 children including 51 males and 9 females, aged 4-15 years, were enrolled. During follow up, normal voiding function were found in 43 cases, VD in 17 cases. It was found that middle to high clinical classification (OR＝6.732, 95%CI:1.854-24.443), multiple surgeries (OR＝3.712, 95%CI:1.133-12.160), associated spinal deformity (OR＝3.297, 95%CI:1.029-10.566) and abnormal postoperative defecation (OR＝4.971, 95%CI:1.387-17.816) were the risk factors of VD after ARM (all P<0.05). Urodynamic study and early intervention should be carried out in children with VD after ARM surgery.

[Analysis of video-urodynamic and clinical features of non-neuropathic lower urinary tract dysfunction in children].

Objective: To analyze the video-urodynamic(VUDS) and clinical features of non-neuropathic lower urinary tract dysfunction (NNLUTD) in children. Methods: Children diagnosed with NNLUTD in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were included. Children with neurological, rectal dysfunction and anatomical abnormalities were excluded. VUDS and urinalysis were performed in all children who were divided into 4 groups accordingly: normal group (Normal group), detrusor overactivity group(DO group), detrusor sphincter dyssynergia group (DSD group) and detrusor underactivity group (DU group). VUDS and clinical features, vesicoureteral reflux (VUR) and urinary tract infections (UTI) were analyzed. Results: A total of 173 children were included in this study, including 103 males and 70 females, aged (7.2±3.3) years. VUDS showed that 46 cases (26.6%) were in Normal group, 63 cases (36.4%) in DO group, 39 cases (22.5%) in DSD group and 25 cases (14.5%) in DU group. Compared with Normal group and DO group, the proportion of VUR in DSD group and DU group was significantly higher [18(46.2%) and 11(44.0%) vs 7(15.0%) and 14(22.2%), all P<0.05],and the proportion of male children was significantly higher than that of female children with VUR only in DO group [12(32.4%) vs 2(7.7%), P=0.020 ]; Compared with DO group, the proportion of UTI in DSD group and DU group was significantly higher [16(41.0%) and 12(48.0%) vs 12(19.0%), all P<0.05], and the proportion of female children was significantly higher than that of male children with UTI in normal group, DO group and DU group [9(45.0%) vs 4(15.4%), 8(30.8%) vs 4(10.8%)and 7(87.5%) vs 5(29.4%), all P<0.05]. The maximum detrusor pressure in DSD group was significantly higher than that in Normal group, DO group and DU group [(95±47) vs (43±18), (56±18) and (12±9)cmH2O, all P<0.05, 1 cmH2O=0.098 kPa).Compared with Normal group and DO group, post void residual in DSD group and DU group was significantly increased [(58±38) and (70±62) vs (8±8) and (8±7)ml, all P<0.05], and the proportion of lower bladder compliance was significantly increased [(15(38.5%) and 11(44%) vs 1(2.2%) and 10(15.9%), all P<0.05]. Compared with normal group, the maximum bladder capacity of DO, DSD and DU group were all significantly decreased [(178±61), (184±81) and (194±93) vs (256±92)ml, all P<0.05]. The proportion of urgency had significant difference in the four groups [13(28.3%) in Normal group, 41(65.1%) in DO group, 22(56.4%) in DSD group and 11(44.0%) in DU group, P=0.001], and the proportion of dysuria had significant difference too [5(10.9%) in Normal group, 18(28.6%) in DO group, 20(51.3%) in DSD group and 15(60.0%) in DU group, P<0.001]. Conclusions: Children with 4 different conditions of NNLUTD have distinct video-urodynamic features. The higher ratio of VUR and UTI in DSD and DU children may be associated with reduced bladder compliance and increased post void residual. VUDS is useful for the diagnosis and treatment of refractory children with NNLUTD.

[Evaluation of the efficacy of a new variable frequency stimulation sacral neuromodulation in the treatment of detrusor hyperactivity with impaired contractility].

A total of 16 detrusor hyperactivity with impaired contractility (DHIC) patients who received 12 weeks remote variable frequency stimulation (VFS) were enrolled at the First Affiliated Hospital of Zhengzhou University from September 2020 to February 2021. The voiding diary, symptom score scales and incidence of complications were completed and recorded at baseline, constant frequency stimulation (CFS) and VFS phases. Compared with the CFS phase, voiding times, urge incontinence times and daily catheterization volume were reduced; average voiding amount and functional bladder capacity increased; and the quality of life score and mental health questionnaire assessment were improved in the VFS phase(all P<0.05). In the end, among all 16 patients, there were 14 whose symptoms had improved, and there were no new complications such as pain or infection at the implantation site, electrode displacement, and electric shock sensation in the stimulation area. VFS-SNM can not only improve the DHIC patients' lower urinary tract symptoms during storage and urination period, but also improve the patients' quality of life and satisfaction of the therapy.