Single-cell analysis reveals a unique microenvironment in peri-implantitis.

AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.

[UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children].

Objective: To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Methods: Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Results: Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G > A accounted for 37.5% (6/16), c.1456T > G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin (t = 5.539, P < 0.05), and indirect bilirubin (t = 5.312, P < 0.05). However, there was no significant difference in direct bilirubin levels (t = 1.223, P > 0.05) and age of onset (t = 0.3611, P > 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T > G homozygous mutations had the highest serum bilirubin levels. Conclusion: The common pathogenic variants of the UGT1A1 gene sequence are c.1456T > G, c.211G > A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

Clinical pharmacist intervention in contraindications of the co-administration of cefoperazone and ambroxol hydrochloride injection.

BACKGROUND: Clinical pharmacists identified contraindications in two cases concerning the co-administration of cefoperazone and ambroxol hydrochloride injection, prompting a thorough investigation. CASE PRESENTATION: Clinically, two cases of contraindications for the co-administration of cefoperazone and ambroxol hydrochloride injection were discovered. After the intervention and analysis by clinical pharmacists, the possible reason could be the precipitation of free alkali due to the immediate administration of ambroxol after the infusion of cefoperazone. Clinical pharmacists suggested avoiding the co-administration of the two and recommended flushing the intravenous lines with 5% glucose injection or 0.9% sodium chloride injection during intravenous infusion to prevent direct drug interaction causing precipitation, thereby reducing the occurrence of adverse events. No adverse events occurred after the intervention, and no harm was caused to the patients. CONCLUSIONS: The co-administration of cefoperazone and ambroxol hydrochloride injection can lead to the precipitation of free alkali, posing a risk of adverse events. Clinical pharmacists' intervention could prevent this interaction. This practice has been shown to be effective, with no subsequent adverse events reported.

[Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease].

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

[The study on biological exposure index of occupational exposure to arsenic and its inorganic compounds].

Objective: To establish biological exposure index (BEI) of occupational exposure to arsenic and its inorganic compounds through occupational epidemiology and the regression analysis of internal and external exposure of workers. Methods: In November 2021, 125 workers with occupational exposure to arsenic and its inorganic compounds and 49 office administrators in a non-ferrous metal smelter in Yunnan Province were selected as the exposure group and control group, respectively. Air samples from the workplace of the study subjects on weekdays were collected and arsenic concentrations were determined. Urine samples were collected in end-of-work weekend and high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect the levels of trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , monomethyl arsenic (MMA) and dimethyl arsenic (DMA) in urine. The correlations between arsenic concentration in the workplace air and arsenic species in urine of workers were analyzed. Arsenic exposure concentration and the level of urinary arsenic (ΣiAs+MMA+DMA) of workers was analyzed by linear regression and the BEI of arsenic and its inorganic compounds in the workplace was proposed based on the results of micronucleus test. Results: The median of time-weighted average concentration (C(TWA)) of arsenic in the workplace air of the exposure group was 0.0116 mg/m(3), and the over-standard rate was 71.2% (89/125) . The concentrations of iAs(3+), iAs(5+), inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) 、MMA、DMA and urinary arsenic in the exposure group were higher than those in the control group at the end of shift, and the differences were statistically significant (P<0.05) . The concentration of arsenic in the workplace air had the strongest correlation with the concentration of urinary arsenic at the end of the shift (r(s)=0.909, P<0.001) . The regression equation was lg (y) =7.662+2.968lg (x) (r=0.821, P<0.05) . According to the occupational exposure limit (OEL) of arsenic in China, the concentration of urinary arsenic in the end-of-work weekend was calculated to be 53.2 µg/L. Combined with the results of micronucleus test, the BEI of occupational exposure to arsenic and its inorganic compounds in the workplace was proposed to be 50 µg/L. Conclusion: The urinary arsenic in the end-of-work weekend can be used as a biomarker of occupational exposure to arsenic, and its BEI is recommended to be 50 µg/L.

[Correlation analysis of urinary arsenic species and health effect indicators of occupational arsenic exposure workers].

Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.

[Preliminary study on the effect of Echinococcus multilocaris on phenotypic transformations of glucose metabolism and polarization types in macrophages].

OBJECTIVE: To investigate the effects of Echinococcus multilocularis on the phenotypic transformations of glucose metabolism, polarization types and inflammatory responses in macrophages, so as to provide insights into elucidation of echinococcosis pathogenesis. METHODS: Bone marrow cells were isolated from C57BL/6J mice at ages of 6 to 8 weeks, and induced into bone marrow-derived macrophages (BMDMs) with mouse macrophage colony-stimulating factor (M-CSF), which served as controls (BMDMs-M0). BMDMs-M0 induced M2 macrophages by interleukin-4 for 24 hours served as the IL-4 induction group, and BMDMs-M0 co-cultured with 2.4 ng/mL E. multilocularis cystic fluid (CF) served as the BMDM-CF co-culture group, while BMDMs-M0 co-cultured with E. multilocularis protoscolex (PSC) at a ratio of 500:1 served as the BMDM-PSC co-culture group. The types of polarization of BMDMs co-cultured with E. multilocularis CF and PSC were analyzed using flow cytometry, and the expression of macrophage markers, inflammatory factors, and glucose metabolism-related enzymes was quantified using fluorescent quantitative real-time PCR (qPCR) and Western blotting assays. RESULTS: There were significant differences among the four groups in terms of Arginase-1 (Arg1) (F = 1 457.00, P < 0.000 1), macrophages-derived C-C motif chemokine 22 (Ccl22) (F = 22 203.00, P < 0.000 1), resistin-like α (Retnla) (F = 151.90, P < 0.000 1), inducible nitric oxide synthase (iNOS) (F = 107.80, P < 0.001), hexokinase (HK) (F = 9 389.00, P < 0.000 1), pyruvate kinase (PK) (F = 641.40, P < 0.001), phosphofructokinase 1 (PFK1) (F = 43.97, P < 0.01), glucokinase (GK) (F = 432.50, P < 0.000 1), pyruvate dehydrogenase kinases1 (PDK1) (F = 737.30, P < 0.000 1), lactic dehydrogenase (LDH) (F = 3 632.00, P < 0.000 1), glucose transporter 1 (GLUT1) (F = 532.40, P < 0.000 1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (F = 460.00, P < 0.000 1), citrate synthase (CS) (F = 5 642.00, P < 0.01), glycogen synthase1 (GYS1) (F = 273.30, P < 0.000 1), IL-6 (F = 1 823.00, P < 0.000 1), IL-10 (F = 291.70, P < 0.000 1), IL-1ß (F = 986.60, P < 0.000 1), and tumor necrosis factor (TNF)-α (F = 334.80, P < 0.000 1) and transforming growth factor (TGF)-ß mRNA expression (F = 163.30, P < 0.001). The proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-PSC co-culture group [(22.87% ±1.48%) vs. (1.70% ±0.17%); t = 24.61, P < 0.001], and the proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-CF co-culture group [(20.07% ±0.64%) vs. (1.93% ±0.25%); t = 45.73, P < 0.001]. The mRNA expression of M2 macrophages markers Arg1, Ccl22 and Retnla was significantly higher in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01), and no significant difference was seen in the mRNA expression of the M1 macrophage marker iNOS among the three groups (P > 0.05), while qPCR assay quantified higher mRNA expression of key glycolytic enzymes HK, PK and PFK, as well as inflammatory factors IL-10, IL-1ß, TNF-α and TGF-ß in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01). Western blotting assay determined higher HK, PK and PFK protein expression in the BMDM-PSC co-culture group than in the control group (all P values < 0.05), and qPCR quantified higher GLUT1, GAPDH and IL-6 mRNA expression in the BMDM-CF co-culture group than in the control group (all P values < 0.05), while higher HK, PK and PFK protein and mRNA expression (all P values < 0.01), as well as lower IL-6 and TNF-α and higher TGF-ß mRNA expression (both P values < 0.05) was detected in the IL-4 induction group than in the control group. Glycolytic stress test showed no significant difference in the extracellular acidification rate (ECAR) of mouse BMDM among the control group, IL-4 induction group and BMDM-PSC co-culture group (F = 124.4, P < 0.05), and a higher ECAR was seen in the BMDM-PSC co-culture group and a lower ECAR was found in the IL-4 induction group than in the control group (both P values < 0.05). CONCLUSIONS: Treatment of E. multilocularis CF or PSC mainly causes polarization of BMDM into M2 macrophages, and phenotypic transformation of glucose metabolism into high-energy and high-glycolytic metabolism, and affects inflammatory responses in BMDM.

The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study.

BACKGROUND: H101, an innovative oncolytic adenovirus, has shown potential in modifying the tumor microenvironment from immunologically 'cold' to 'hot'. When combined with nivolumab, a programmed cell death protein 1 inhibitor, this synergy may offer substantial therapeutic benefits beyond the capabilities of each agent alone. PATIENTS AND METHODS: In this pilot study, we assessed the efficacy and safety of combining H101 with nivolumab in advanced hepatocellular carcinoma (HCC) patients who failed prior systemic therapy. The participants received initial oncolytic virus (OV) pretreatment with intratumoral H101 injections (5.0 × 1011 vp/0.5 ml/vial, two vials per lesion) on days 1 and 3. Combination therapy started on day 8, with H101 administered every 2 or 4 weeks and nivolumab (240 mg) injections every 2 weeks. Treatment continued up to 12 months or until disease progression, intolerable toxicity, consent withdrawal, or study conclusion. The primary endpoint was the objective response rate (ORR). RESULTS: Between March 2020 and March 2022, 18 of 21 screened patients were assessable, showing an ORR of 11.1% [two cases of partial response (PR) and five cases of stable disease], with extrahepatic injections often leading to favorable outcomes. The disease control rate stood at 38.9%, with a 6-month survival rate of 88.9%. Median progression-free survival was 2.69 months, and overall survival (OS) was 15.04 months. Common adverse events included low-grade fever (100%) and pain related to centesis (33.3%), and no grade 3/4 events were reported. Significantly, local H101 injection showed potential in reversing immune checkpoint inhibitor resistance, evidenced by over 2.5 years of extended OS in PR cases with low α-fetoprotein. Additionally, decreasing neutrophil-to-lymphocyte ratio during OV pretreatment may predict positive outcomes. CONCLUSIONS: This study demonstrates the potential efficacy of combining H101 with nivolumab in treating refractory advanced HCC, with well-tolerated toxicities.

Comparison of different dosages of propofol combined with its equivalent alfentanil in outpatient abortion: a prospective, double-blinded, randomized trial.

OBJECTIVE: This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. PATIENTS AND METHODS: The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 µg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality. RESULTS: The ED50 and the ED95 values of alfentanil were 3.37 µg·kg-1 (95% CI: 2.58-3.97 µg·kg-1) and 4.68 µg·kg-1 (95% CI: 4.04-9.32 µg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes. CONCLUSIONS: The combination of 2.5 mg·kg-1 propofol and 4.68 µg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 µg·kg-1 alfentanil without increasing additional risks associated with anesthesia.

Application of tensor fascia lata perforator flap in head and neck reconstruction.

The aim of this study was to describe the authors' experience in head and neck reconstruction with the tensor fascia lata perforator flap (TFLPF). Between April 2009 and August 2020, 16 patients underwent head and neck reconstruction with a TFLPF. The flaps were designed in a vertical or transverse fashion based on perforators traveling along the medial or lateral aspect of the posterior edge of the tensor fascia lata muscle. Clinical details and postoperative results were recorded and analyzed. The size of the flap ranged from 7 × 5 cm2 to 25 × 9 cm2. The perforators were mostly septocutaneous (11 patients), allowing a simple and straightforward dissection of the perforator and TFLPF in most patients. There were either one or two perforators in all cases. The overall flap survival rate was 100%. All of the flaps healed uneventfully with no delayed wound healing or donor site dysfunction. Follow-up ranged from 18 to 120 months, during which all patients experienced satisfactory functional and aesthetic results, without serious complications at either the recipient or donor site. The TFLPF is a pliable and reliable flap that could be a first choice in selected head and neck reconstruction cases.

Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

Predictive value of hematological parameters in cirrhotic patients with open umbilical hernia repair.

PURPOSE: Patients with liver cirrhosis sometimes suffer from high recurrence rates and postoperative complications. We previously reported that platelet-related hematological parameters are associated with the outcomes after incisional herniorrhaphy, and aim to evaluate the predictive value of these criteria in cirrhotic patients undergoing open umbilical herniorrhaphy. METHODS: This is a retrospective study. The data of 95 cirrhotic patients undergoing open umbilical herniorrhaphy were analyzed. Patients were grouped based on the recurrence and defined hematological values. Platelet-multiple-lymphocyte index (PLM), neutrophil-leukocyte ratio, lymphocyte-monocyte ratio, platelet-neutrophil ratio, systemic immune-inflammation index, and aspartate aminotransferase-leukocyte ratio values were calculated based on preoperative blood analyses. The outcomes were obtained from hospital records and follow-up calls to patients. RESULTS: Using cutoff values acquired by the Youden Index, we found a PLM value < 27.9, and the history of inguinal herniorrhaphy were revealed to be statistically significant in the recurrence based on univariant and multivariant analyses (p < 0.05). We further divided patients into two groups based on the cutoff value of PLM and found that a PLM value < 27.9 was significantly associated with the recurrence of incisional hernias (p = 0.018) and the occurrence of postoperative foreign sensation (p = 0.044), and tended to result in other postoperative complications such as cardiopathy, respiratory infection, hypoproteinemia, and hepatic diseases (p = 0.089). CONCLUSION: The preoperative hematological values, especially PLM, may indicate the outcomes in cirrhotic patients after open umbilical herniorrhaphy. Accurate identification of risks may alert the intraoperative and postoperative care for patients.

The generation of genuine quadripartite Einstein-Podolsky-Rosen steering in an optical superlattice.

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.

Biomarkers, signaling pathways, and programmed cell death in acute lung injury and its treatment with Traditional Chinese Medicine: a narrative review.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening, high-mortality lung diseases associated with acute and severe inflammation of the lungs. However, research on diagnostic markers and signaling pathways associated with ALI/ARDS is lacking, and no specific drug therapy is available for ALI/ARDS. Therefore, in this study, biomarkers and signaling pathways associated with ALI/ARDS were summarized to provide a reference for future clinical and research work. A review of Traditional Chinese Medicine for the treatment or prevention of ALI/ARDS is also presented to provide a reference for further development of Traditional Chinese Medicine. In summary, this review will help raise awareness of ALI/ARDS and provide insight into the future exploitation of Traditional Chinese Medicine.