Pregnant outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer. / æŠ—ç€ä¸ç‚¹æŠ—ä½“é˜³æ€§æ‚£è€ ä½“å¤–å—ç²¾ç»“å±€åˆ†æž.

OBJECTIVES: To analyze the pregnant outcomes in patients with positive anti-centromere antibody (ACA) receiving in vitro fertilization (IVF) -embryo transfer (ET) and natural conception. METHODS: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received in vitro fertilization-embryo transfer therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnant outcomes were analyzed using self-matching analysis. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. RESULTS: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the double pronuclei rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immunosuppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant difference in miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. CONCLUSIONS: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Overexpression of Phosphoserine Aminotransferase (PSAT)-Enhanced Cadmium Resistance and Accumulation in Duckweed (Lemna turionifera 5511).

Cadmium (Cd) hampers plant growth and harms photosynthesis. Glutamate (Glu) responds to Cd stress and activates the Ca2+ signaling pathway in duckweed, emphasizing Glu's significant role in Cd stress. In this study, we overexpressed phosphoserine aminotransferase (PSAT), a crucial enzyme in Glu metabolism, in duckweed. We investigated the response of PSAT-transgenic duckweed to Cd stress, including growth, Glu metabolism, photosynthesis, antioxidant enzyme activity, Cd2+ flux, and gene expression. Remarkably, under Cd stress, PSAT-transgenic duckweed prevented root abscission, upregulated the expression of photosynthesis ability, and increased Chl a, Chl b, and Chl a + b levels by 13.9%, 7%, and 12.6%, respectively. Antioxidant enzyme activity (CAT and SOD) also improved under Cd stress, reducing cell membrane damage in PSAT-transgenic duckweeds. Transcriptomic analysis revealed an upregulation of Glu metabolism-related enzymes in PSAT-transgenic duckweed under Cd stress. Moreover, metabolomic analysis showed a 68.4% increase in Glu content in PSAT duckweed exposed to Cd. This study sheds novel insights into the role of PSAT in enhancing plant resistance to Cd stress, establishing a theoretical basis for the impact of Glu metabolism on heavy metal tolerance in plants.

SARS-CoV-2 infection in pregnant patients on TNFα inhibitor: Real-life data with a review of literature.

Tumor necrosis factor alpha (TNFα) is involved in the occurrence of negative pregnancy outcomes. The study aimed to evaluate the safety and efficacy of the immunosuppressive TNFα inhibitors (TNFαi) in the treatment of patients with a history of recurrent reproductive failure in the context of COVID-19 pandemics. We reviewed 85 patients who received TNFαi (certolizumab pegol) during Mainland China's first wave of COVID-19 pandemic, from 21st Nov 2022-11 th Jan 2023. We also collected corresponding data from 130 pregnant patients who never used TNFαi for comparison. There were no significant differences in the history of previous pregnancy loss, miscarriage, embryo implantation failure, comorbidities and doses of COVID-19 vaccination. 82.2% and 87.7% pregnant patients contracted primary COVID-19 with symptoms in TNFαi group and no-TNFαi group. Duration of symptoms was significantly longer in TNFαi group and the incidences of cough and lethargy was significantly higher in TNFαi group. Both groups reported similar severity to same-aged close contacts, similar rates of other symptoms and hospitalization. No deaths were reported. In the in vitro fertilization (IVF) subgroup, we achieved a biochemical pregnancy loss rate of 17.4%, miscarriage rate of 21.7%, ongoing pregnancy rate and live birth rate of 34.2%. COVID-19 did not influence the live birth rate. We concluded that TNFαi administration in pregnancy was not associated with increased susceptivity to and severity of COVID-19. However, TNFαi users showed more prominent symptoms and longer recovery time. The pregnancy outcomes with TNFαi in such high-risk group for pregnancy loss was satisfactory.

Novel MEI1 mutations cause chromosomal and DNA methylation abnormalities leading to embryonic arrest and implantation failure.

This study presents a case of a female infertile patient suffering from embryonic arrest and recurrent implantation failure. The primary objective was to assess the copy number variations (CNVs) and DNA methylation of her embryos. Genetic diagnosis was conducted by whole-exome sequencing and validated through Sanger sequencing. CNV evaluation of two cleavage stage embryos was performed using whole-genome sequencing, while DNA methylation and CNV assessment of two blastocysts were carried out using whole-genome bisulfite sequencing. We identified two novel pathogenic frameshift variants in the MEI1 gene (NM_152513.3, c.3002delC, c.2264_2268 + 11delGTGAGGTATGGACCAC) in the proband. These two variants were inherited from her heterozygous parents, consistent with autosomal recessive genetic transmission. Notably, two Day 3 embryos and two Day 6 blastocysts were all aneuploid, with numerous monosomy and trisomy events. Moreover, global methylation levels greatly deviated from the optimized window of 0.25-0.27, measuring 0.344 and 0.168 for the respective blastocysts. This study expands the mutational spectrum of MEI1 and is the first to document both aneuploidy and abnormal methylation levels in embryos from a MEI1-affected female patient presenting with embryonic arrest. Given that females affected by MEI1 mutations might experience either embryonic arrest or monospermic androgenetic hydatidiform moles due to the extrusion of all maternal chromosomes, the genetic makeup of the arrested embryos of MEI1 patients provides important clues for understanding the different disease mechanisms of the two phenotypes.

Prioritizing ecological restoration in hydrologically sensitive areas to improve groundwater quality.

Greening is the optimal way to mitigate climate change and water quality degradation caused by agricultural expansion and rapid urbanization. However, the ideal sites to plant trees or grass to achieve a win-win solution between the environment and the economy remain unknown. Here, we performed a nationwide survey on groundwater nutrients (nitrate nitrogen, ammonia nitrogen, dissolved reactive phosphorus) and heavy metals (vanadium, chromium, manganese, iron, cobalt, nickel, copper, arsenic, strontium, molybdenum, cadmium, and lead) in China, and combined it with the global/national soil property database and machine learning (random forest) methods to explore the linkages between land use within hydrologically sensitive areas (HSAs) and groundwater quality from the perspective of hydrological connectivity. We found that HSAs occupy approximately 20 % of the total land area and are hotspots for transferring nutrients and heavy metals from the land surface to the saturated zone. In particular, the proportion of natural lands within HSAs significantly contributes 8.0 % of the variability in groundwater nutrients and heavy metals in China (p < 0.01), which is equivalent to their contribution (8.8 %) at the regional scale (radius = 4 km, area = 50 km2). Increasing the proportion of natural lands within HSAs improves groundwater quality, as indicated by the significant reduction in the concentrations of nitrate nitrogen, manganese, arsenic, strontium, and molybdenum (p < 0.05). These new findings suggest that prioritizing ecological restoration in HSAs is conducive to achieving the harmony between the environment (improving groundwater quality) and economy (reducing investment in area management).

Therapeutic vaccination with lentiviral vector in HBV-persistent mice and two inactive HBsAg carriers.

BACKGROUND & AIMS: Immunotherapy for chronic hepatitis B virus (HBV) infection has not yet demonstrated sufficient efficacy. We developed a non-integrative lentiviral-vectored therapeutic vaccine for chronic hepatitis B and tested its antiviral effects in HBV-persistent mice and two inactive HBsAg carriers. METHODS: Lentiviral vectors (LVs) encoding the core, preS1, or large HBsAg (LHBs) proteins of HBV were evaluated for immunogenicity in HBV-naïve mice and therapeutic efficacy in a murine model of chronic HBV infection. In addition, two inactive HBsAg carriers each received two doses of 5×107 transduction units (TU) or 1×108 TU of lentiviral-vectored LHBs (LV-LHBs), respectively. The endpoints were safety, LHBs-specific T-cell responses, and serum HBsAg levels during a 24-week follow-up. RESULTS: In the mouse models, LV-LHBs was the most promising in eliciting robust antigen-specific T cells and in reducing the levels of serum HBsAg and viral load. By the end of the 34-week observation period, six out of ten (60%) HBV-persistent mice vaccinated with LV-LHBs achieved serum HBsAg loss and significant depletion of HBV-positive hepatocytes in the liver. In the two inactive HBsAg carriers, vaccination with LV-LHBs induced a considerable increase in the number of peripheral LHBs-specific T cells in one patient, and a weak but detectable response in the other, accompanied by a sustained reduction of HBsAg (-0.31 log10 IU/ml and -0.46 log10 IU/ml, respectively) from baseline to nadir. CONCLUSIONS: A lentiviral-vectored therapeutic vaccine for chronic HBV infection demonstrated the potential to improve HBV-specific T-cell responses and deplete HBV-positive hepatocytes, leading to a sustained loss or reduction of serum HBsAg. IMPACT AND IMPLICATIONS: Chronic HBV infection is characterized by an extremely low number and profound hypo-responsiveness of HBV-specific T cells. Therapeutic vaccines are designed to improve HBV-specific T-cell responses. We show that immunization with a lentiviral-vectored therapeutic HBV vaccine was able to expand HBV-specific T cells in vivo, leading to reductions of HBV-positive hepatocytes and serum HBsAg.

Three-dimensional architecture of granulosa cell derived from oocyte cumulus complex, revealed by FIB-SEM.

The oocyte cumulus complex is mainly composed of an oocyte, the perivitelline space, zona pellucida and numerous granulosa cells. The cumulus granulosa cells (cGCs) provide a particularly important microenvironment for oocyte development, regulating its growth, maturation and meiosis. In this study, we studied the internal structures and cell-to-cell connections of mouse cGCs using focused ion beam scanning electron microscopy (FIB-SEM). We reconstructed three-dimensional models to display characteristic connections between the oocyte and cGCs, and to illustrate various main organelles in cGCs together with their interaction relationship. A special form of cilium identified in granulosa cell was never reported in previous literature.

Corrigendum: Getting pregnant with congenital adrenal hyperplasia: assisted reproduction and pregnancy complications. A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fendo.2022.982953.].

The Role of Peritoneal Immunity in Peritoneal Endometriosis and Related Infertility.

Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms.

Dual laser-assisted hatching: an effective technique to salvage low-grade cleavage-stage embryos and harvest day 7 blastocysts.

To investigate whether repeating laser-assisted hatching (LAH) procedure on day 6 low-grade cleavage-stage embryos (LGCEs) helps blastulation. A total of 579 cycles with LGCEs from 2019 to 2022 was retrospectively reviewed. In 323 cycles, single LAH producing small holes (10 µm) was performed on LGCEs on day 4 (D4-LAH). In 256 cycles with persistent LGCEs despite D4-LAH, a repeat LAH procedure was performed on day 6 (Dual-LAH) with a bigger hole (30 µm). We compared day 7 blastocyst formation rate, usable blastocyst rate, and good grade blastocyst rate from these day 6 LGCEs between the two groups. Compared to the D4-LAH group, the Dual-LAH group had both higher day 7 blastocyst formation rate (9.4% vs. 3.0%, p < 0.001) and higher day 7 usable blastocyst rates (7.4% vs. 2.1%, p < 0.001). For persistent LGCEs despite single LAH, performing a repeat LAH on day 6 increased day 7 blastocyst formation rate.

The Antimicrobial Potential and Aquaculture Wastewater Treatment Ability of Penaeidins 3a Transgenic Duckweed.

With the development of aquaculture, wastewater treatment and diseases have been paid more and more attention. The question of how to improve the immunity of aquatic species, as well as treat aquaculture wastewater, has become an urgent problem. In this study, duckweed with a high protein content (37.4%) (Lemna turionifera 5511) has been employed as a feedstock for aquatic wastewater treatment and the production of antimicrobial peptides. Penaeidins 3a (Pen3a), from Litopenaeus vannamei, were expressed under the control of CaMV-35S promoter in duckweed. Bacteriostatic testing using the Pen3a duckweed extract showed its antibacterial activity against Escherichia coli and Staphylococcus aureus. Transcriptome analysis of wild type (WT) duckweed and Pen3a duckweed showed different results, and the protein metabolic process was the most up-regulated by differential expression genes (DEGs). In Pen3a transgenic duckweed, the expression of sphingolipid metabolism and phagocytosis process-related genes have been significantly up-regulated. Quantitative proteomics suggested a remarkable difference in protein enrichment in the metabolic pathway. Pen3a duckweed decreased the bacterial number, and effectively inhibited the growth of Nitrospirae. Additionally, Pen3a duckweed displayed better growth in the lake. The study showed the nutritional and antibacterial value of duckweed as an animal feed ingredient.

Visualizing in situ viral replication across the natural history of chronic HBV infection.

BACKGROUND AND AIMS: Chronic HBV infection evolves through different phases. Interactions between viral replication and the host immune response in the liver underlie the pathogenesis of this disease. The aim of this study was to directly visualize the HBV replication intermediates at a single-cell resolution inscribed on morphological changes corresponding to disease activity. METHODS: A set of archived formalin-fixed paraffin-embedded liver needle biopsies from treatment-naïve patients were collected and categorized into phases according to the American Association for the Study of the Liver Diseases (AASLD) guidelines. HBV RNA and DNA were detected using in situ hybridization assays. RESULTS: The hepatocytes were ubiquitously infected in subjects with immune tolerance, and their percentage was gradually decreased in immune-active and inactive chronic hepatitis B phases. HBV-infected hepatocytes were prone to localize close to fibrous septa. The subcellular distribution of signals was able to distinguish hepatocytes with productive infection from those harboring HBV integrants and transcriptionally inactive covalently closed circular DNAs. A smaller number of hepatocytes with productive infection and more harboring transcriptionally inactive covalently closed circular DNA or HBV integrants became apparent in the inactive chronic hepatitis B phase. CONCLUSION: An atlas of in situ characteristics of viral-host interactions for each phase is described, which sheds light on the nature of viral replication and disease pathogenesis among the phases of chronic HBV infection.

The impact of social identity conflict on planning horizons.

In the current increasingly complex environment, people often hold multiple social identities. For example, an Asian American may identify as both an American and an Asian descendant, and a mixed-race person may simultaneously identify with both races. Whenever the different identities are simultaneously activated and give conflicting behavioral direction, people experience social identity conflict. Seven studies, using both measured and manipulated social identity conflict in surveys, secondary data, and controlled experiments, showed that social identity conflict shortens one's planning horizon in future-oriented choices. This effect occurs because the conflict between one's multiple social identities undermines the clarity in self-perception, and in turn weakens the enduring sense of self in the temporal dimension. Consequently, it anchors people's planning horizon to a more proximate future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogues.

BACKGROUND: Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. METHODS: A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. RESULTS: Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. CONCLUSIONS: We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.

Preventing Growth Stagnation and Premature LH Surge Are the Keys to Obtaining a Viable Embryo in Monofollicular IVF Cycles: A Retrospective Cohort Study.

How LH levels influenced the outcomes of monofollicular IVF cycles using different stimulation protocols was controversial. In this single-center, retrospective study, we analyzed 815 monofollicular IVF cycles between 2016−2022 using natural cycle (NC), medroxyprogesterone acetate (MPA) or clomiphene citrate (CC) in addition to human menopausal gonadotropin (hMG), with or without GnRH antagonist. A viable embryo was obtained in 35.7% of all cycles. Growth stagnation and premature LH surge are two markedly negative factors for obtaining viable embryos (odds ratios of 0.12 [0.08−0.65], p < 0.0001 and 0.33 [0.26,0.42], p < 0.0001, respectively). NC/hMG cycles are prone to premature LH surge (40.4%), yielding a significantly lower opportunity of obtaining embryos (24.7%, p = 0.029). The administration of GnRH antagonist on the background of MPA resulted in a significant decrease in LH levels (from 2.26 IU/L to −0.89 IU/L relative to baseline, p = 0.000214), leading to a higher risk of growth stagnation (18.6%, p = 0.007). We hypothesized that the abrupt decline of LH might increase the risk of apoptosis in granulosa cells. We proposed a "marginal effect" framework to emphasize that the change of LH was the key to its bioactivity, rather than the traditional "window" concept with fixed cutoff values of a threshold and a ceiling.

Meta-analysis of robotic versus open pancreaticoduodenectomy in all patients and pancreatic cancer patients.

Purposes: To compare perioperative outcomes of robotic pancreaticoduodenectomy (RPD) to open pancreaticoduodenectomy (OPD) using evidence from cohort studies. Methods: Outcomes of interest include operative time, blood loss, R0 resection rate, lymph nodes harvested, overall complication rate, pancreatic fistula rate, delayed gastric emptying rate and 90-day mortality. Results: 6 prospective studies and 15 retrospective studies were included. Five of these studies were limited to patients with pancreatic cancer. Operative time was significantly longer in RPD (WMD: 64.60 min; 95% CI: 26.89 to 102.21; p = 0.001). Estimated blood loss was lower in RPD (WMD: -185.44 ml; 95% CI: -239.66 to -131.21; p < 0.001). Overall complication rates (OR: 0.66; 95% CI: 0.44 to 0.97; p < 0.001) and pancreatic fistula rate (OR: 0.67; 95% CI: 0.55 to 0.82; p < 0.001) were both lower in RPD. Length of hospital stay was longer in OPD (WMD: -1.90; 95% CI: -2.47 to -1.33). 90-day mortality was lower in RPD [odds ratio (OR): 0.77; 95% CI: 0.45 to 0.95; p = 0.025]. Conclusion: At current level of evidence, RPD is a safer alternative than OPD with regard to post-operative outcomes and blood loss. However, in terms of oncological outcomes RPD show no advantage over OPD, and the cost of RPD was higher. In general, RPD is now considered a reliable technology, but high-quality randomized controlled trial (RCT) studies are still needed to support this conclusion.

The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: a multicentre randomised controlled trial.

BACKGROUND & AIMS: The strategies of adding on or switching to peginterferon (PEG-IFN) improved the serological response rates in patients with chronic hepatitis B (CHB) who had previously experienced treatment with nucleos(t)ide analogues. However, robust data on which combination strategy is more effective remain lacking. METHODS: In this multicentre, parallel, open-label, randomised, controlled trial, patients with HBeAg-positive CHB who were treated with entecavir ≥2 years, and had hepatitis B surface antigen (HBsAg) <3000 IU/ml, HBeAg <200S/CO and HBV DNA <50 IU/ml were randomly assigned in a 1:1:1 ratio to add on PEG-IFN, switch to PEG-IFN or continue entecavir monotherapy for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48. RESULTS: A total of 153 patients were randomised into three treatment arms (50 in add-on, 52 in switch-to and 51 in monotherapy). Compared with continuous entecavir monotherapy, both add-on and switch-to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, p = 0.007; 19.2% vs. 2.0%, p = 0.005, respectively), HBeAg loss (24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013, respectively), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001, respectively), and higher HBsAg reduction (-0.90 vs. -0.06 log10 IU/ml, p < 0.001; -0.92 vs. -0.06 log10 IU/ml, p < 0.001, respectively) at week 48. The efficacy was comparable between add-on and switch-to arms (p > 0.05). Adverse events were mainly related to PEG-IFN but generally tolerable. CONCLUSION: In patients with CHB who achieved virological response with long-term entecavir, both adding on and switching to PEG-IFN are alternative strategies resulting in higher rates of HBeAg seroconversion and HBsAg reduction than continuous entecavir. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR-IPR-17012055).

Getting pregnant with congenital adrenal hyperplasia: Assisted reproduction and pregnancy complications. A systematic review and meta-analysis.

Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to genitalia abnormalities, anovulation, unreceptive endometrium and metabolic disturbances. Despite those challenges, many live births have been reported. In this systematic review, we focused on the key to successful assisted reproduction strategies and the potential pregnancy complications. We did a systematic literature search of Pubmed, Medline and Scopus for articles reporting successful pregnancies in CAH other than 21-hydroxylase deficiency, and found 25 studies reporting 39 pregnancies covering deficiency in steroidogenic acute regulatory protein, 17α-hydroxylase/17,20-lyase, 11ß-hydroxylase, P450 oxidoreductase, cytochrome b5 and 3ß-hydroxysteroid dehydrogenase. We summarized various clinical manifestations and tailored reproduction strategy for each subtype. Furthermore, a meta-analysis was performed to evaluate the pregnancy complications of CAH patients. A total of 19 cross-sectional or cohort studies involving 1311 pregnancies of classic and non-classic CAH patients were included. Surprisingly, as high as 5.5% (95% CI 2.3%-9.7%) of pregnancies were electively aborted, and the risk was significantly higher in those studies with a larger proportion of classic CAH than those with only non-classical patients (8.43% (4.1%-13.81%) VS 3.75%(1.2%-7.49%)), which called for better family planning. Pooled incidence of miscarriage was 18.2% (13.4%-23.4%) with a relative risk (RR) of 1.86 (1.27-2.72) compared to control. Glucocorticoid treatment in non-classical CAH patients significantly lowered the miscarriage rate when compared to the untreated group (RR 0.25 (0.13-0.47)). CAH patients were also more susceptible to gestational diabetes mellitus, with a prevalence of 7.3% (2.4%-14.1%) and a RR 2.57 (1.29-5.12). However, risks of preeclampsia, preterm birth and small for gestational age were not significantly different. 67.8% (50.8%-86.9%) CAH patients underwent Cesarean delivery, 3.86 (1.66-8.97) times the risk of the control group. These results showed that fertility is possible for CAH patients but special care was necessary when planning, seeking and during pregnancy. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=342642, CRD42022342642.

[Expert statement on the construction criteria of critical care department in municipal and district designated hospitals under the pandemic prevention and control].

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that "dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.

A Novel Homozygous Missense Mutation of PIEZO1 Leading to Lymphatic Malformation-6 Identified in a Family With Three Adverse Pregnancy Outcomes due to Nonimmune Fetal Hydrops.

Lymphatic malformation-6 (LMPHM6) is a rarer form of nonimmune hydrops that often manifests as widespread lymphedema involving all segments of the body, namely, subcutaneous edema, intestinal/pulmonary lymphangiectasia, chylothoraces, and pleural/pericardial effusions. Here, we detected one rare and previously unobserved homozygous missense variant in PIEZO1 (c.5162C>G, p.Ser1721Trp) as a novel genetic cause of autosomal recessive LMPHM6, in a family with three adverse pregnancy outcomes due to nonimmune fetal hydrops. Although, the loss-of-function mutations such as those usually including nonsense, frameshift, splice site, and also fewer missense variants in PIEZO1 have been proved to lead to LMPHM6, among these, the biallelic homozygous mutations resulting in the loss of function of PIEZO1 have not been reported before. Here, we first strongly implicated impaired PIEZO1 function-associated LMPHM6 with a homozygous missense mutation in PIEZO1.