Objective To investigate the clinical effect of posterior femoral composite tissue flap pedicled with inferior gluteal artery for repair of huge sacrococcygeal pressure injuries.Methods The clinical data of 11 patients with huge sacrococcygeal pressure injuries admitted to our hospital were retrospectively analyzed,with a mean wounds area of(205.3±15.3)cm2,and the depth of the wounds all reached the sacrococcygeal bone surface with partial sacrococcygeal necrosis.The inferior gluteal artery and its perforating branch were investigated with ultrasonic Doppler flow detector before operation,the posterior femoral composite tissue flap pedicled with inferior gluteal artery was designed according to the wound surface,and then the chronic sacrococcygeal wound was repaired.The operation time,intraoperative blood loss,wound healing,postoperative skin flap survival and occurrence of complications were recorded.The skin flap color,temperature and two-point discernability were monitored to evaluate skin flap sensory sensitivity.The visual analog scale(VAS)was used to evaluate the satisfaction of appearance.Results The operation time of patients was(2.8±0.1)hours and the intraoperative blood loss was(235.4±10.2)mL.The posterior femoral composite tissue flap pedicled with inferior gluteal artery of all the 11 patients survived.The distal part of the flap was necrotic in 1 case,which healed well after local debridement and suturing by amplification;other wounds healed well in the first stage without complications such as infection,fat liquefaction or hematoma.The skin flap has good color,soft texture,and good elasticity,with good healing in the donor area.There were significant differences in the skin flap temperature,two-point discernability and VAS score of appearance satisfaction between 12 months after operation and other time points(P＜0.05).Conclusion The posterior femoral composite tissue flap pedicled with inferior gluteal artery has a constant blood supply,without damage to the main blood vessels.It can be transposed at anterograde or retrograde direction,with simple operation and less damage,which can reconstruct flap sense,and has significant clinical efficacy in repairing huge sacrococcygeal pressure injuries.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).

【Objective】 To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. 【Methods】 The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. 【Results】 The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. 【Conclusion】 There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.

Objective: To analyze the incidence of early severe complications following bariatric and metabolic surgery and the experience of their diagnosis, treatment, and risk factors. Methods: In this retrospective observational study, the clinical data of 4255 patients who underwent bariatric and metabolic surgery between May 2010 and May 2022 in the Department of Bariatric and Metabolic Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. Among these patients, 1125 were male and 3130 were female. The mean age and body mass index (BMI) of the patients at the time of operation were 31.3±4.5 years and 36.5±6.4 kg/m², respectively. Regarding surgical type, 2397 patients underwent sleeve gastrectomy (SG), 489 underwent Roux-en-Y gastric bypass (RYGB), 1028 underwent sleeve gastrectomy plus jejunojejunal bypass (SG+JJB), and 341 underwent single anastomosis duodenal switch (SADS). The inclusion criteria were patients (1) with a Clavien-Dindo grade of ≥III; (2) who were undergoing SG, RYGB, SG-JJB, or SADS; and (3) who had complete clinical data. The exclusion criteria were patients (1) undergoing revisional surgery and (2) other operations during the bariatric and metabolic surgery. The Clavien-Dindo classification was used to analyze the incidence of early severe postoperative complications and their prognosis. Early severe postoperative complications were defined as Clavien-Dindo ≥ III complications within 30 days after surgery. Meanwhile, multivariate logistic regression model was used to identify risk factors of the complications. Results: Summary of early severe complications following bariatric and metabolic surgery: (1) of the 4255 patients, 22 (12 male and 10 female) exhibited early severe complications (0.52%). The mean age and BMI of these patients were 41.1±9.9 years and 36.9±8.2 kg/m², respectively. Preoperatively, 7 patients had hypertension, 10 had type 2 diabetes mellitus, 1 had respiratory failure, and 1 had heart failure. The severe complications included 9 patients (0.21%) with grade IIIa, 11 (0.26%) with grade IIIb, 1 (0.02%) with grade IVa, and 1 (0.02%) with grade V complications. The incidences of severe postoperative complications in the different surgical procedures were 0.17% for SG (4/2397), 0.61% for RYGB (3/489), 0.58% for SG+JJB (6/1028), and 2.64% for SADS (9/341). The common severe complications were leakage (0.28%, 12 patients), bleeding (0.14%, 6 patients), and obstruction (0.05%, 2 patients). (2) Management of complications: Grade IIIa complications (including eight patients with leakage and one with severe inflammation) were treated with antibiotics, nasogastric and nutritional tube placements, and CT-guided drainage. For grade IIIa complications, five patients with bleeding were treated with reoperation, and all the patients recovered; four patients with leakage were treated with reoperation, wherein three were converted to RYGB and one patient underwent resuturing of the leakage site; two patients with obstruction were treated with adhesiolysis. The patient with grade IVa complication (including respiratory failure complicated with acid aspiration) was treated in the ICU. For the grade V complication, bleeding in a patient with SG+JJB was treated with reoperation, which confirmed the bleeding of short gastric vessels. Unfortunately, the patient died. (3) Risk factor analysis of early severe complications: univariate analysis detected that sex, age, type 2 diabetes mellitus, operation time, and surgical type were associated with postoperative complications (P<0.05). However, multivariate analysis indicated that an age of ≥31.3 years (odds ratio [OR] = 5.423, 95% confidence interval [CI]: 1.004-29.278, P=0.049) and surgical type (SADS: OR = 19.758, 95%CI: 5.803-67.282, P<0.001; RYGB: OR = 9.752, 95%CI: 2.456-38.723, P=0.001; SG+JJB: OR = 5.706, 95%CI: 1.966- 16.559, P=0.001) were independent risk factors of early severe complications following bariatric and metabolic surgery. Conclusion: Bariatric and metabolic surgery is safe. Its common postoperative complications include leakage, bleeding, and obstruction, which require early detection, diagnosis, and treatment to improve treatment outcomes. Age and surgical type are independent risk factors of early severe complications following bariatric and metabolic surgery.
Adult ; Anti-Bacterial Agents ; Bariatric Surgery/adverse effects* ; Diabetes Mellitus, Type 2/surgery* ; Female ; Gastrectomy/methods* ; Gastric Bypass/adverse effects* ; Humans ; Male ; Obesity, Morbid/surgery* ; Postoperative Complications/epidemiology* ; Respiratory Insufficiency/etiology* ; Retrospective Studies ; Risk Factors ; Treatment Outcome

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

Grade evaluation method of quality constant is a kind of grading method for Chinese medicinal materials and decoction pieces,combining the external morphological index and internal content index. This method was used in this paper for grade evaluation of Gardeniae Fructus. By measuring the morphological and content indexes of 14 batches of Gardeniae Fructus,a method for calculating the quality constant of fruits was established,and the grade evaluation criteria were formed. At the same time,the NO inhibition effect of different grades of Gardeniae Fructus samples on RAW264. 7 cells induced by LPS was determined to investigate the relationship between the quality grade and pharmacodynamics of decoction pieces. The results showed that the quality constants of Gardeniae Fructus decoction piece samples ranged from 1. 46 to 4. 42. If the percentage quality constant ≥80% was classified into first-class,50%-80%as second-class and the rest as third-class,the quality constant was ≥3. 54 for first-class,2. 21-3. 54 for second-class and <2. 21 for third-class Gardeniae Fructus decoction pieces. The pharmacodynamic results showed that the pharmacodynamic intensity was positively correlated with the grade,which also proved the rationality of the grade evaluation method of quality constant.
Animals ; Drugs, Chinese Herbal ; analysis ; standards ; Fruit ; chemistry ; Gardenia ; chemistry ; Mice ; Quality Control ; RAW 264.7 Cells

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.
Adult Germline Stem Cells/metabolism* ; Animals ; Cell Proliferation/physiology* ; Gene Knockdown Techniques ; Male ; Mice ; Proteome ; Repressor Proteins/metabolism* ; Testis/metabolism* ; Wnt Signaling Pathway/physiology*

OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.