GLUT1 is a highly efficient L-fucose transporter.

Understanding L-fucose metabolism is important because it is used as a therapy for several congenital disorders of glycosylation. Exogenous L-fucose can be activated and incorporated directly into multiple N- and O-glycans via the fucose salvage/recycling pathway. However, unlike for other monosaccharides, no mammalian L-fucose transporter has been identified. Here, we functionally screened nearly 140 annotated transporters and identified GLUT1 (SLC2A1) as an L-fucose transporter. We confirmed this assignment using multiple approaches to alter GLUT1 function, including chemical inhibition, siRNA knockdown, and gene KO. Collectively, all methods demonstrate that GLUT1 contributes significantly to L-fucose uptake and its utilization at low micromolar levels. Surprisingly, millimolar levels of D-glucose do not compete with L-fucose uptake. We also show macropinocytosis, but not other endocytic pathways, can contribute to L-fucose uptake and utilization. In conclusion, we determined that GLUT1 functions as the previously missing transporter component in mammalian L-fucose metabolism.

A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction.

SLC37A4 encodes an endoplasmic reticulum (ER)-localized multitransmembrane protein required for transporting glucose-6-phosphate (Glc-6P) into the ER. Once transported into the ER, Glc-6P is subsequently hydrolyzed by tissue-specific phosphatases to glucose and inorganic phosphate during times of glucose depletion. Pathogenic variants in SLC37A4 cause an established recessive disorder known as glycogen storage disorder 1b characterized by liver and kidney dysfunction with neutropenia. We report seven individuals who presented with liver dysfunction multifactorial coagulation deficiency and cardiac issues and were heterozygous for the same variant, c.1267C>T (p.Arg423∗), in SLC37A4; the affected individuals were from four unrelated families. Serum samples from affected individuals showed profound accumulation of both high mannose and hybrid type N-glycans, while N-glycans in fibroblasts and undifferentiated iPSC were normal. Due to the liver-specific nature of this disorder, we generated a CRISPR base-edited hepatoma cell line harboring the c.1267C>T (p.Arg423∗) variant. These cells replicated the secreted abnormalities seen in serum N-glycosylation, and a portion of the mutant protein appears to relocate to a distinct, non-Golgi compartment, possibly ER exit sites. These cells also show a gene dosage-dependent alteration in the Golgi morphology and reduced intraluminal pH that may account for the altered glycosylation. In summary, we identify a recurrent mutation in SLC37A4 that causes a dominantly inherited congenital disorder of glycosylation characterized by coagulopathy and liver dysfunction with abnormal serum N-glycans.

First report of root rot in Trichosanthes kirilowii (Chinese cucumber) caused by Fusarium sulawesiense in China.

Trichosanthes kirilowii (Chinese cucumber) is one of the important perennial herbaceous vines in China, with putative pharmacological activities including anti-tumor and lowering blood lipids. In July 2022, T. kirilowii plants with brownish roots and chlorotic leaves were observed in several orchards in Qianshan, Anhui province, China (30°34'N, 116° 30'E). The disease incidence reached approximately 10% within an area spanning 20 ha, and was higher in poorly drained orchards. To investigate this root rot disease, five symptomatic plants were collected from the diseased orchards in Qianshan. Subsequently, small sections of the diseased roots were surface sterilized using 1% sodium hypochlorite and 75% ethanol for 45 seconds each. Then, sterilized roots were placed onto PDA (20% diced potato, 2% glucose, and 1.5% agar, and distilled water) and incubated at 28℃ in the dark for 6 days. A total of eight isolates with similar morphology were obtained and purified by single spore culturing. Two representative isolates (QSJ4 and QSJ5) were chosen for further analysis. When grown on PDA, the surface of each colony was white with dense aerial mycelium and pale orange color in the center with a white edge on the reverse side. Macroconidia produced on carnation leaf agar plates were falcate, slightly curved, and 3 to 5 septate, with papillate apical cells and indistinct basal cells. Macroconidia were 17.4-42.3 × 2.4-5.8 µm (n = 100). Microconidia were ellipsoidal in shape, slightly curved or not curved, and most were 1-septate, 9.6-16.7 × 1.5-3.8 µm (n = 40). The identity was determined by sequencing four loci (i. e., ITS, CAL, EF1-α and RPB2) from two representative isolates (Liu et al. 1999; O'Donnell et al. 1998, 2000; Reeb et al. 2004; White et al. 1990). Sequences were deposited in GenBank [ITS (OR267397, OR267398), CAL (OR296634, OR296635), EF1-α (OR296637, OR296638) and RPB2 (OR296640, OR296641)]. A phylogenetic analysis was performed with three loci (CAL, EF1-α, RPB2) comprising a concatenated dataset of 68 strains in the Fusarium incarnatum-equiseti species complex (Han et al., 2023). The results showed that isolates QSJ4 and QSJ5 clustered closely together with reference strains of F. sulawesiense. Pathogenicity tests were conducted by inoculating three-week-old healthy T. kirilowii seedings (cv. Wanlou No. 9) cultivated in substrate soil in pots with a diameter of 17 cm and a height of 10.5 cm. A 20 mL aliquot of spore suspension (106 conidia/mL) of F. sulawesiense was inoculated to the roots of potted seedlings by irrigation. Each strain was inoculated onto three seedlings. The potted seedlings were inoculated with sterile water as the negative control. Inoculated seedlings were incubated in a growth chamber at 25℃ and 75% relative humidity. After one week, typical symptoms of root necrosis and leaf chlorosis were observed on the inoculated seedlings. Disease symptoms were not observed on the control seedlings. All seedlings showing root necrosis and leaf chlorosis caused by the inoculations were subjected to fungal isolation, and the results showed that the reisolated colonies matched the inoculated ones for morphologies and ITS sequences. Fusarium sulawesiense has been previously reported to cause disease on Cucumis melo L. in Brazil (Medeiros Araujo et al. 2021), Musa acuminata Colla in south Sulawesi (Maryani et al. 2019), Luffa aegyptiaca Miller and Musa nana Lour. in China (Wang et al. 2019). To our knowledge, this is the first report of F. sulawesiense causing Fusarium root rot of T. kirilowii in China.

Time-Resolved Extensional Rheo-NMR Spectroscopy for Investigating Polymer Nanocomposites under Deformation.

Understanding the microstructure change of polymer nanocomposites (PNCs) under elongation deformation at the molecular level is the key to coupling structure-property relationships of PNCs. In this study, we developed our recently proposed in situ extensional rheology NMR device, Rheo-spin NMR, which can simultaneously obtain both the macroscopic stress-strain curves and the microscopic molecular information with the total sample weight of ∼6 mg. This enables us to conduct a detailed investigation of the evolution of the interfacial layer and polymer matrix in nonlinear elongational strain softening behaviors. A quantitative method is established for in situ analysis of (1) the fraction of the interfacial layer and (2) the network strand orientation distribution of the polymer matrix based on the molecular stress function model under active deformation. The results show that for the current highly filled silicone nanocomposite system, the influence of the interfacial layer fraction on mechanical property change during small amplitude deformation is quite minor, while the main role is reflected in rubber network strand reorientation. The Rheo-spin NMR device and the established analysis method are expected to facilitate the understanding of the reinforcement mechanism of PNC, which can be further applied to understand the deformation mechanism of other systems, i.e., glassy and semicrystalline polymers and the vascular tissues.

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.

Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed the loss of a single sialic acid. Western blotting on patient-derived fibroblasts revealed reduced COG3 and COG4. Further experiments showed delayed retrograde vesicular recycling in patient cells. This report adds to the knowledge of the COG-CDG network by providing collective evidence for a COG3-CDG rare disease trait and implicating a likely pathology of the disorder as the perturbation of Golgi trafficking.

A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation.

The conserved oligomeric Golgi (COG) complex is involved in intracellular vesicular transport, and is composed of eight subunits distributed in two lobes, lobe A (COG1-4) and lobe B (COG5-8). We describe fourteen individuals with Saul-Wilson syndrome, a rare form of primordial dwarfism with characteristic facial and radiographic features. All affected subjects harbored heterozygous de novo variants in COG4, giving rise to the same recurrent amino acid substitution (p.Gly516Arg). Affected individuals' fibroblasts, whose COG4 mRNA and protein were not decreased, exhibited delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in sera and fibroblasts from affected subjects was not notably altered, but decorin, a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. In summary, we define a specific heterozygous COG4 substitution as the molecular basis of Saul-Wilson syndrome, a rare skeletal dysplasia distinct from biallelic COG4-CDG.

Chain dynamics and crystalline network structure of poly[R-3-hydroxybutyrate-co-4-hydroxybutyrate] as revealed by solid-state NMR.

The chain dynamics and crystalline network structure of poly[R-3-hydroxybutyrate-co-4-hydroxybutyrate] (P(3HB-co-4HB)) were systematically investigated by the combination of various solid-state NMR techniques. High-resolution 13C cross-polarization (CP) and direct-polarization (DP) MAS with selective recycle delay times were first used to check the presence or absence of the 4HB unit in the crystalline domain. The results show that the 4HB unit is excluded from the crystalline domain. Afterward, 1H MAS Nuclear Overhauser Effect Spectroscopy (NOESY) with different mixing times was used, which shows that no micro-phase separation exists in the amorphous domain. 1H magic-sandwich-echo (MSE)-FID at elevated temperature shows the absence of motions on a timescale of 100 µs and below in the crystalline domain, as evidenced by the invariant second moment M2 of the proton line shape. Finally, the crystalline based network density was characterized directly by magic and polarization echo (MAPE)-double quantum (DQ) NMR, which shows a significant decreasing tendency after 80 °C. Such a decreasing crystalline network density, together with the reduced relaxation time, results in the significant decrement of the maximum stretch ratio and modulus in the high-temperature region.

Network structure of swollen iodine-doped poly(vinyl alcohol) amorphous domain as characterized by low field NMR.

The network structure in the amorphous domain of swollen iodine-doped poly(vinyl alcohol) (PVA) was systematically investigated by low-field (LF) NMR techniques to reveal the PVA-iodine complex formation mechanism. Three PVA-iodine complexes were obtained under different iodine concentrations (ciodine) of KI/I2 solution: (i) ciodine < 0.1 M: PVA-I3-/I5- complex only exists in the non-crystalline region, (ii) 0.1 M < ciodine < 1 M: formation of PVA-I3- complex I, and (iii) ciodine > 1 M: formation of PVA-I3- complex II. It was found that there is no intermediate-magnitude chain motion of PVA under dyeing conditions to induce the substance exchange, as evidenced by the unchanged second moment M2 (∼1.2 × 104 m s-2) at elevated temperature (<380 K). The introduction of iodine ions can affect the chain mobility of the interphase and mobile regions. With increasing ciodine, the chain dynamics become more restricted, as detected by the faster decay of the T2 relaxometry results, which further accelerates the complexation process. The residual dipolar coupling strength, Dres, obtained by the more quantitative double-quantum (DQ) NMR, increases abruptly at ciodine > 1 M. This suggests more constraints form in the amorphous network for the PVA-I3- complex II system. The constant defects fraction further reveals that the complexation prefers to happen along the tie chains. These results supply a possible formation pathway for the PVA-iodine complexes.

A case report of community-acquired Raoultella ornithinolytica infection in a healthy, young individual.

BACKGROUND: Raoultella ornithinolytica is a Gram-negative bacillus that resembles Klebsiella. This bacterium is present in many soil and aquatic environments and is a major causative agent of healthcare-associated infections (HAIs) in medical staff. Clinically, it has been reported to contribute to nosocomial infections in patients that include but are not limited to gastrointestinal, skin, and genitourinary tract infections. These complications are most common in hospitalized patients with underlying immunodeficiency, multiple comorbidities, or those receiving invasive surgery. CASE PRESENTATION: We present a case of a 25-year-old patient with a R. ornithinolytica infection. The patient had no history of any disease. Her main complaints were high fever, a scattered maculopapular rash, and superficial lymph node enlargement (SLNE). Peripheral blood samples were collected for high-throughput sequencing analysis to identify pathogenic microorganisms. The results confirmed a R. ornithinolytica infection, which was treated successfully using meropenem. Loratadine was also administered to treat the patient's compromised skin condition caused by an allergic reaction. CONCLUSIONS: To our knowledge, this is the first case of a systemic maculopapular rash and superficial lymphadenopathy caused by a R. ornithinolytica infection acquired at the community level. Based on this case, we recommend a combination of antibiotic and antiallergic drugs to treat a R. ornithinolytica infection and associated allergic reaction to the bacteria.

Defining the clinical phenotype of Saul-Wilson syndrome.

PURPOSE: Four patients with Saul-Wilson syndrome were reported between 1982 and 1994, but no additional individuals were described until 2018, when the molecular etiology of the disease was elucidated. Hence, the clinical phenotype of the disease remains poorly defined. We address this shortcoming by providing a detailed characterization of its phenotype. METHODS: Retrospective chart reviews were performed and primary radiographs assessed for all 14 individuals. Four individuals underwent detailed ophthalmologic examination by the same physician. Two individuals underwent gynecologic evaluation. Z-scores for height, weight, head circumference and body mass index were calculated at different ages. RESULTS: All patients exhibited short stature, with sharp decline from the mean within the first months of life, and a final height Z-score between -4 and -8.5 standard deviations. The facial and radiographic features evolved over time. Intermittent neutropenia was frequently observed. Novel findings included elevation of liver transaminases, skeletal fragility, rod-cone dystrophy, and cystic macular changes. CONCLUSIONS: Saul-Wilson syndrome presents a remarkably uniform phenotype, and the comprehensive description of our cohort allows for improved understanding of the long-term morbidity of the condition, establishment of follow-up recommendations for affected individuals, and documentation of the natural history into adulthood for comparison with treated patients, when therapeutics become available.

Manipulation of Chain Entanglement and Crystal Networks of Biodegradable Poly(butylene adipate-co-butylene terephthalate) During Film Blowing through the Addition of a Chain Extender: An In Situ Synchrotron Radiation X-ray Scattering Study.

One prerequisite for the large-scale application of biodegradable polymers is the manipulation of macroscopic performances of commercially available biopolymers during processing according to different real service requirements. Herein, the microstructural evolution of poly(butylene adipate-co-butylene terephthalate) (PBAT) modified by chain extender during film blowing was investigated by in situ synchrotron radiation X-ray scattering to unveil the origin of different performances. The chain dynamics difference induced by the chain extender was first characterized by the rheological measurement and 1H Multiple Quantum (MQ) NMR. It shows that the terminal relaxation is significantly slowed down, while the locally segmental dynamics is not apparently changed. With the assistance of the custom-built film blowing apparatus, the microstructure right above the die exit (D = 13-165 mm) was in situ, simultaneously captured by small- and wide-angle scattering (SAXS/WAXS), where four distinct regimes can be defined. Only the PBAT melt signals are found in regime I, whereas the formation of the mesomorphic domains as shown by the SAXS streaks appearing in regime II. The crystal shows up in regime III, where the WAXS signal appears. A dramatic increment of the crystallinity is found in regime III, which contributes to the continuous increasing bubble modulus with the formation of the crystal-based network. Such a crystal-based network is filled with crystals in regime IV, where the diameter of the PBAT bubble remains constant. The addition of the chain extender is found to significantly influence the structural evolution within different regimes. These dynamics and structure information could supply general guidance for bubble stability improvement and modification of macroscopic performances of biodegradable polymer products.

Functional regions of the peroxin Pex19 necessary for peroxisome biogenesis.

The peroxins Pex19 and Pex3 play an indispensable role in peroxisomal membrane protein (PMP) biogenesis, peroxisome division, and inheritance. Pex19 plays multiple roles in these processes, but how these functions relate to the structural organization of the Pex19 domains is unresolved. To this end, using deletion mutants, we mapped the Pex19 regions required for peroxisome biogenesis in the yeast Pichia pastoris Surprisingly, import-competent peroxisomes still formed when Pex19 domains previously believed to be required for biogenesis were deleted, although the peroxisome size was larger than that in wild-type cells. Moreover, these mutants exhibited a delay of 14-24 h in peroxisome biogenesis. The shortest functional N-terminal (NTCs) and C-terminal constructs (CTCs) were Pex19 (aa 1-150) and Pex19 (aa 89-300), respectively. Deletions of the N-terminal Pex3-binding site disrupted the direct interactions of Pex19 with Pex3, but preserved interactions with a membrane peroxisomal targeting signal (mPTS)-containing PMP, Pex10. In contrast, deletion of the C-terminal mPTS-binding domain of Pex19 disrupted its interaction with Pex10 while leaving the Pex19-Pex3 interactions intact. However, Pex11 and Pex25 retained their interactions with both N- and C-terminal deletion mutants. NTC-CTC co-expression improved growth and reversed the larger-than-normal peroxisome size observed with the single deletions. Pex25 was critical for peroxisome formation with the CTC variants, and its overexpression enhanced their interactions with Pex3 and aided the growth of both NTC and CTC Pex19 variants. In conclusion, physical segregation of the Pex3- and PMP-binding domains of Pex19 has provided novel insights into the modular architecture of Pex19. We define the minimum region of Pex19 required for peroxisome biogenesis and a unique role for Pex25 in this process.

Salinicola tamaricis sp. nov., a heavy-metal-tolerant, endophytic bacterium isolated from the halophyte Tamarix chinensis Lour.

A Gram-stain-negative, rod-shaped bacterium, strain F01T, was isolated from leaves of Tamarix chinensis Lour. The isolate grew optimally at 30 °C, at pH 7.0 and with 5.0 % (w/v) NaCl, and showed a high tolerance to manganese, lead, nickel, ferrous ions and copper ions. The major fatty acids were C18 : 1ω7c and C16 : 0, and the predominant respiratory quinone was Q-9. Polar lipids were dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminoglycolipids and phospholipids. The DNA G+C content was 65.8 %. Based on multilocus phylogenetic analysis, strain F01T belonged to the genus Salinicola, with highest 16S rRNA gene sequence similarity to Salinicola peritrichatus CGMCC 1.12381T (97.7 %). The level of DNA-DNA hybridization between strain F01T and closely related Salinicola strains was well below 70 %. According to the phenotypic, genetic and chemotaxonomic data, strain F01T is considered to represent a novel species in the genus Salinicola, for which the name Salinicola tamaricis sp. nov. is proposed. The type strain is F01T (=CCTCC AB 2015304T=KCTC 42855T).

Larsenimonas suaedae sp. nov., a moderately halophilic, endophytic bacterium isolated from the halophyte Suaeda salsa.

A moderately halophilic, Gram-stain-negative, non-endospore-forming endophytic bacterium designated strain ST307T was isolated from the euhalophyte Suaeda salsa in Dongying, China. Strain ST307T was aerobic, rod-shaped, motile and orange-yellow-pigmented. The organism grew at NaCl concentrations of 0.6-20 % (w/v) (optimum 5-6 %, w/v), at temperatures of 5-45 °C (optimum 35 °C) and at pH 5-9 (optimum pH 7-8). It accumulated poly-ß-hydroxybutyric acid and produced exopolysaccharides. The major fatty acids were C18 : 1ω7c/C18 : 1ω6c, C16 : 0 and C16 : 1ω7c/C16 : 1ω6c. The predominant lipoquinone was ubiquinone Q-9. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, a glycoaminolipid and a phosphoglycoaminolipid. The DNA G+C content was 60.5 mol%. Phylogenetic analyses of 16S rRNA gene sequences and concatenated atpA, rpoD and secA gene sequences revealed that the strain represents a member of the genus Larsenimonas. The closest related type strain was Larsenimonas salina M1-18T. Mean DNA-DNA relatedness values between strain ST307T and the related species L. salina M1-18T, Chromohalobacter beijerinckii DSM 7218T, C. canadensis DSM 6769T, C. israelensis DSM 6768T, C. marismortui CGMCC 1.2321T, C. nigrandesensis DSM 14323T, C. salexigens DSM 3043T and C. sarecensis DSM 15547T were 15±2-45±1 %. On the basis of phenotypic, chemotaxonomic and molecular features, strain ST307T clearly represents a novel species of the genus Larsenimonas. The name Larsenimonassuaedae sp. nov. is proposed, with ST307T (=CGMCC 1.8902T=DSM 22428T) as the type strain.

Biomimetic human eyes in adaptive lenses with conductive gels.

To investigate the imaging effect, adaptive robust lenses are prepared by sealing transparent liquid or gel. Lenses are fabricated using the negative-pressure method, which is a benefit for a stable biconvex shape. Under the action of an electric field, the soft lens deforms following the dielectric elastomer actuator (DEA). DE (dielectric elastomer) membranes expand in the plane perpendicular to the electric field lines. The toroidal driving area leads to a decrease in lens diameter and an increase in convex curvature. Therefore, the focal length of the lens becomes shorter. The experimental measurement utilizes the double focal length method. As a result, the largest focal length change that could be achieved was 44.7% (190 mm→105 mm) of the soft lens using a DEA with carbon grease electrodes. Furthermore, the ECG (electrocardiogram) conductive gel could replace traditional carbon grease for DEA electrodes in optics. This type of transparent electrode is creatively applied to a biomedical lens. Under the same conditions, the electrostriction rate in a DEA with ECG gel was achieved at 33%, which was greater than that of 28% in a DEA coupled with carbon grease electrode. Adaptive lenses have characteristics such as easy fabrication, low cost, and strong operability, and they possess great potential application value in biomedical feild.

The Swedish COG6-CDG experience and a comprehensive literature review.

Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in COG6 were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c.238G>A; p.Glu80Lys) is undescribed. On the other hand, a previously undescribed homozygous duplication (c.1793_1795dup) was deemed the cause of the disease. To confirm the pathogenicity of the variants, we treated patient and control fibroblasts with the ER-Golgi transport inhibitor Brefeldin-A and show that patient cells manifest a significantly slower anterograde and retrograde ER-Golgi transport.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

[Analysis of the risk factors related to prognosis of severe intra-abdominal infection in surgical intensive care unit].

OBJECTIVE: To investigate the risk factors related to prognosis of patients with severe intra-abdominal infection (SIAI) in surgical intensive care unit (SICU). METHODS: Clinical data of 69 patients with SIAI, who were hospitalized during January 2008 and April 2011 in SICU, were analyzed retrospectively. According to the outcome at discharge from SICU, 69 patients were divided into two groups: the survivors 42 cases; the deceased 27 cases. The potential risk factors of SIAI patients in SICU were analyzed by univariate analysis and logistic regression analysis. RESULTS: Univariate analysis showed that average acute physiology and chronic health evaluation II (APACHEII) scores (the survival group: 11.76 ± 3.48; the death group: 17.12 ± 4.50), inadequate treatment of intra-abdominal infection (3 survivors, 21 deceased), inadequate initial antibiotic treatment (3 survivors, 15 deceased) and septic shock (24 survivors, 27 deceased) were risk factors for mortality (all P < 0.01). Logistic regression analysis showed that average APACHEII scores over 15 [relative risk (RR): 6.846, P value: 0.044] and insufficient treatment of intra-abdominal infection (RR: 21.319, P value: 0.018) were the independent risk factors in SIAI patients in SICU. CONCLUSION: To decrease the mortality of SIAI patients in SICU, more attention should be paid to monitor APACHEII scores and to handle intra-abdominal infection adequately.