[Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease].

Objective: To analyze the clinical characteristics of patients with Vibrio vulnificus infection, share diagnosis and treatment experience, and establish a rapid diagnosis procedure for this disease. Methods: This study was a retrospective case series study. From January 2009 to November 2022, 11 patients with Vibrio vulnificus infection who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of Guangdong Provincial People's Hospital Affiliated to Southern Medical University. The gender, age, time of onset of illness, time of admission, time of diagnosis, route of infection, underlying diseases, affected limbs, clinical manifestations and signs on admission, white blood cell count, hemoglobin, platelet count, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, procalcitonin, albumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and blood sodium levels on admission, culture results and metagenomic next-generation sequencing (mNGS) results of pathogenic bacteria and the Vibrio vulnificus drug susceptibility test results during hospitalization, treatment methods, length of hospital stay, and outcomes of all patients were recorded. Comparative analysis was conducted on the admission time and diagnosis time of patients with and without a history of exposure to seawater/marine products, as well as the fatality ratio and amputation of limbs/digits ratio of patients with and without early adequate antibiotic treatment. For the survived patients with hand involvement, the hand function was assessed using Brunnstrom staging at the last follow-up. Based on patients' clinical characteristics and treatment conditions, a rapid diagnosis procedure for Vibrio vulnificus infection was established. Results: There were 7 males and 4 females among the patients, aged (56±17) years. Most of the patients developed symptoms in summer and autumn. The admission time was 3.00 (1.00, 4.00) d after the onset of illness, and the diagnosis time was 4.00 (2.00, 8.00) d after the onset of illness. There were 7 and 4 patients with and without a history of contact with seawater/marine products, respectively, and the admission time of these two types of patients was similar (P>0.05). The diagnosis time of patients with a history of contact with seawater/marine products was 2.00 (2.00, 5.00) d after the onset of illness, which was significantly shorter than 9.00 (4.25, 13.00) d after the onset of illness for patients without a history of contact with seawater/marine products (Z=-2.01, P<0.05). Totally 10 patients had underlying diseases. The affected limbs were right-hand in 8 cases, left-hand in 1 case, and lower limb in 2 cases. On admission, a total of 9 patients had fever; 11 patients had pain at the infected site, and redness and swelling of the affected limb, and 9 patients each had ecchymosis/necrosis and blisters/blood blisters; 6 patients suffered from shock, and 2 patients developed multiple organ dysfunction syndrome. On admission, there were 8 patients with abnormal white blood cell count, hemoglobin, and albumin levels, 10 patients with abnormal CRP, procalcitonin, and NT-proBNP levels, 5 patients with abnormal creatinine and blood sodium levels, and fewer patients with abnormal platelet count, ALT, and AST levels. During hospitalization, 4 of the 11 wound tissue/exudation samples had positive pathogenic bacterial culture results, and the result reporting time was 5.00 (5.00, 5.00) d; 4 of the 9 blood specimens had positive pathogenic bacterial culture results, and the result reporting time was 3.50 (1.25, 5.00) d; the mNGS results of 7 wound tissue/exudation or blood samples were all positive, and the result reporting time was 1.00 (1.00, 2.00) d. The three strains of Vibrio vulnificus detected were sensitive to 10 commonly used clinical antibiotics, including ciprofloxacin, levofloxacin, and amikacin, etc. A total of 10 patients received surgical treatment, 4 of whom had amputation of limbs/digits; all patients received anti-infection treatment. The length of hospital stay of 11 patients was (26±11) d, of whom 9 patients were cured and 2 patients died. Compared with that of the 6 patients who did not receive early adequate antibiotic treatment, the 5 patients who received early adequate antibiotic treatment had no significant changes in the fatality ratio or amputation of limbs/digits ratio (P>0.05). In 3 months to 2 years after surgery, the hand function of 8 patients was assessed, with results showing 4 cases of disabled hands, 2 cases of incompletely disabled hands, and 2 cases of recovered hands. When a patient had clinical symptoms of limb redness and swelling and a history of contact with seawater/marine products or a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection. Conclusions: Vibrio vulnificus infection occurs most frequently in summer and autumn, with clinical manifestations and laboratory test results showing obvious infection characteristics, and may be accompanied by damage to multiple organ functions. Both the fatality and disability ratios are high and have a great impact on the function of the affected limbs. Early diagnosis is difficult and treatment is easily delayed, but mNGS could facilitate rapid detection. For patients with red and swollen limbs accompanied by a history of contact with seawater/marine products or with a pre-examination triage RiCH score of Vibrio vulnificus sepsis ≥1, the etiological testing should be initiated immediately to quickly diagnose Vibrio vulnificus infection.

Active Suppression of Quantum Dephasing in Resonantly Driven Ensembles.

We have used quantum control to suppress the impact of random atom positions on coherent population transfer within atom pairs, enabling the observation of dipole-dipole driven Rabi oscillations in a Rydberg gas with hundreds of atoms. The method exploits the reduced coupling-strength sensitivity of the off-resonant Rabi frequency, and coherently amplifies the achievable population transfer in analogy to quasi-phase-matching in nonlinear optics. Simulations reproduce the experimental results and demonstrate the potential benefits of the technique to other many-body quantum control applications.

The diagnostic efficiency of diffusion-weighted imaging in placenta accreta spectrum: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the diagnostic efficiency of diffusion-weighted imaging (DWI) in patients with placenta accreta spectrum (PAS). MATERIALS AND METHODS: The present study searched on PubMed, Embase, OVID, Cochrane, Scopus and CNKI, Chinese Bio-Medical Literature, VIP, Wanfang, Duxiu, databases for studies related to the diagnostic performance of DWI for PAS from inception to December 2022. The pooled sensitivity, the pooled specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnosis odds ratios (DOR) were calculated by Meta-disc 1.4 and STATA 16.0. RESULTS: A total of 11 studies met the criteria and were included in the meta-analysis. The effect indexes of DWI in combined PAS were as follows. The pooled sensitivity was 0.670 (0.619-0.719). The pooled specificity was 0.720 (0.661-0.773). The pooled LR+ was 2.161 (1.454-3.211). The pooled LR- was 0.413 (0.280-0.609). The pooled AUC was 0.7841, and Q* was 0.7221. The pooled diagnostic ratio DOR was 6.713 (2.981-15.118). Subgroup analysis showed that four studies used T2-weighted imaging (T2WI) + DWI to diagnose PAS, and the pooled AUC was 0.9822. CONCLUSIONS: The results showed that DWI had high sensitivity and specificity in the diagnosis of PAS. Furthermore, T2WI+DWI has higher diagnostic efficacy than DWI alone in the diagnosis of PAS. Therefore, it is necessary to set T2WI+DWI as a routine sequence for PAS, and T2WI+DWI should be a routine method for the daily diagnosis of PAS.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Single-cell RNA sequencing-guided fate-mapping toolkit delineates the contribution of yolk sac erythro-myeloid progenitors.

Erythro-myeloid progenitors of the yolk sac that originates during early embryo development has been suggested to generate tissue-resident macrophage, mast cell, and even endothelial cell populations from fetal to adult stages. However, the heterogeneity of erythro-myeloid progenitors (EMPs) is not well characterized. Here, we adapt single-cell RNA sequencing to dissect the heterogeneity of EMPs and establish several fate-mapping tools for each EMP subset to trace the contributions of different EMP subsets. We identify two primitive and one definitive EMP subsets from the yolk sac. In addition, we find that primitive EMPs are decoupled from definitive EMPs. Furthermore, we confirm that primitive and definitive EMPs give rise to microglia and other tissue-resident macrophages, respectively. In contrast, only Kit+ Csf1r- primitive EMPs generate endothelial cells transiently during early embryo development. Overall, our results delineate the contribution of yolk sac EMPs more clearly based on the single-cell RNA sequencing (scRNA-seq)-guided fate-mapping toolkit.

[Clinical characteristics and analysis of risk factors for heart injuries in 55 patients with lightning injury on plateau in Tibet Autonomous Region].

Objective: To explore the clinical characteristics and treatment outcomes of patients with lightning injury on plateau in Tibet Autonomous Region, and to analyze the risk factors for heart injuries in these patients. Methods: A retrospective case series study was conducted. From January 2008 to July 2023, 55 patients with lightning injury who met the inclusion criteria were admitted to the General Hospital of PLA Tibet Military Area Command. The gender, age, ethnicity, time of injury, location of injury (average altitude), activity at the time of injury, the occurrence of thermal burns on the body surface, the occurrence of complication, the occurrence of combined injury, underlying disease or physiological process before injury, length of hospital stay, treatment outcome, and effective rate of treatment were recorded. The patients were divided into juvenile group (11 cases), young group (28 cases), middle-aged group (14 cases), and elderly group (2 cases) according to age bracket, then the gender and ethnicity distribution of patients in the 4 groups were compared. According to the occurrence of heart injuries at admission, the patients were divided into heart injury group (44 cases) and non-heart injury group (11 cases), then the gender, age, ethnicity, average altitude of location of injury, length of hospital stay, the occurrence of complication, the occurrence of combined injury, site of thermal burns on the body surface, and area of thermal burns on the body surface in patients were compared between the two groups. Data were statistically analyzed with Mann-Whitney U test, chi-square test, or Fisher's exact probability test. The multivariate logistic regression analysis was conducted to screen the independent risk factors for heart injury in patients with lightning injury. Results: Among the 55 patients aged 10-68 years, 39 were male and 16 were female, including 47 Tibetans and 8 Hans. There were no statistically significant differences in gender or ethnicity distribution of patients among the 4 groups with different age brackets (P>0.05). Lightning injuries occurred from May to September, which mostly occurred in June and July. The incidence of lightning injury was higher in Chengguan District of Lhasa City (average altitude of 3 650 m) and Baqing County of Naqu City (average altitude of 4 500 m), being 20.0% (11/55) and 16.4% (9/55), respectively. A total of 96.4% (53/55) of the patients were engaged in outdoor activities when injured, such as grazing, digging Cordyceps, and harvesting highland barley. Among the 55 patients, 46 (83.6%) cases had thermal burns on the body surface, with burn area mainly being not more than 10% total body surface area and burn depth mainly being deep partial-thickness. Fifty-two (94.5%) patients had complications, with heart injury being the most common complication (44 cases, 80.0%). Twenty-two (40.0%) patients had 11 combined injuries, and traumatic brain injury was the most common combined injury. Seventeen (30.9%) patients had 11 underlying diseases or physiological processes before injury. The length of hospital stay of patients was 9 (5, 17) d. Among the 55 patients, 14 cases were cured and discharged, 40 cases were improved, and 1 case died, with effective rate of treatment of 98.2%. Compared with those in non-heart injury group, the proportion of complication occurrence (χ2=12.28), the proportion of trunk burns (χ2=5.15), and the average altitude of location of injury (Z=-2.38) of patients in heart injury group were increased significantly (P<0.05), while there were no significant changes in the other indicators (P>0.05). Multivariate logistic regression analysis showed that the average altitude at the location of injury was the independent risk factor for heart injury in patients with lightning injury (with odds ratio of 3.28, 95% confidence interval of 1.35-7.99, P<0.05). Conclusions: Lightning injuries on plateau in Tibet Autonomous Region mainly occur from May to September, with an average altitude of 4 500 m at the location of injury. Patients with lightning injury are injured when participating outdoor activities, and the affected patients are mainly mainly young male Tibetans. Most of the injuries are mild burns. Lightning injuries are complex and have many complications, with heart injury being the most common one. The average altitude at the location of injury is the independent risk factor for heart injury in patients with lightning injury.

[The efficacy of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery].

Objective: To examine the safety and effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Methods: The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up. Results: The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth and that the false lumen disappeared or weakened. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively (W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively (W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion: The use of thin struct bare stents for SIDSMA is safety and efficacy.

[Comparative study of surgical effects on patients with mixed deafness and otosclerosis with different air bone conduction differences].

Objective: To analyze the surgical efficacy of patients with mixed hearing loss and otosclerosis with different air bone gap (ABG) before surgery, and to provide reference for the prognosis evaluation of otosclerosis surgery. Methods: The clinical data of 108 cases(116 ears) of otosclerosis who had undergone stapes fenestration technique artificial stapes implantation in Xiangya Hospital of Central South University from November 2013 to May 2020 and had mixed hearing loss before surgery were collected, including 71 women(76 ears)and 37 men (40 ears), with an average age of 38.5 years. According to preoperative pure tone audiometry ABG, they were divided into three groups: group S, 15 dB≤ABG<31 dB, a total of 39 ears; group M, 31 dB≤ABG<46 dB, a total of 58 ears; and group L, ABG≥46 dB, 19 ears in total. The hearing outcomes of three groups of patients at 6-12 months after surgery were compared and analyzed using SPSS 24.0 statistical software. Results: A total of 3 patients (group S: 2 cases; group L: 1 case) experienced severe sensorineural hearing loss after surgery and were not included in the statistical analysis. After surgery, the pure tone hearing threshold of patients with otosclerosis in each group was significantly improved compared to before surgery, with an average air conduction threshold improvement of(21.6±13.4) dB. The difference between before and after surgery was statistically significant(t=17.13, P<0.01). The average bone conduction threshold improved by(3.7±7.6) dB, and the difference was statistically significant before and after surgery(t=5.20, P<0.01). The postoperative ABG was(18.3±9.3) dB, which was significantly reduced compared to preoperative(36.2±8.6)dB. Among the three groups of patients, the L group had the highest improvement in air conduction threshold[(29.9±10.8)dB], while the S group had the lowest improvement[(15.7±11.4)dB]. There was no statistically significant difference in post operative pure tone hearing thresholds between the three groups(P>0.05). The postoperative ABG in group S was the smallest[(16.5±9.0)dB], while in group L, the postoperative ABG was the largest[(20.5±10.0)dB]. Compared with group S, group M and group L still had a large residual ABG at 2 000 Hz after surgery. The bone conduction threshold of both S and M groups improved to some extent after surgery compared to before (P<0.01). Conclusions: Surgery can benefit patients with mixed hearing loss and otosclerosis with different preoperative ABG. Patients with small preoperative ABG have better surgical results and ideal ABG closure at all frequencies after surgery. Patients with large preoperative ABG can significantly increase the gas conduction threshold during surgery, but certain frequencies of ABG may still be left behind after surgery. The improvement effect of surgery on bone conduction threshold is not significant. Patients should be informed of treatment methods such as hearing aids based on their actual situation for selection.

[Diagnostic value of nasal nitric oxide for children with primary ciliary dyskinesia].

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

Resección transuretral en bloque vs. resección transuretral convencional para el cáncer de vejiga primario no músculo-infiltrante: metaanálisis / En-bloc transurethral resection vs. conventional transurethral resection for primary non-muscle invasive bladder cancer: A meta-analysis

Introducción Se realizó un metaanálisis para evaluar el efecto de la resección transuretral en bloque en comparación con la resección transuretral convencional para el cáncer de vejiga primario no músculo-infltrante. Métodos Se realizó una búsqueda sistemática en la literatura hasta enero de 2022 y se incluyeron 28 estudios con 3.714 sujetos con cáncer de vejiga primario no músculo-infltrante al inicio del estudio; a 1.870 de ellos se les efectuó una resección transuretral en bloque y a 1.844 una resección transuretral convencional para el cáncer de vejiga primario no músculo-infltrante. Se calculó la odds-ratio (OR) y la diferencia de medias (DM) con intervalos de confianza (IC) del 95% para evaluar el efecto de una y otra en el cáncer primario de vejiga no invasivo por métodos dicotómicos o continuos con un modelo de efectos aleatorios o fijos. Resultados La resección transuretral en bloque obtuvo valores significativamente menores en términos de recurrencia a los 24 meses (OR: 0,63; IC 95%: 0,50-0,78; p<0,001), tiempo de sondaje (DM: –0,66; IC 95%: –1,02-[–0,29]; p<0,001); duración de la estancia hospitalaria (DM: –0,95; IC 95%: –1,55-[–0,34]; p=0,002), tiempo de irrigación vesical postoperatoria (DM: –6,06; IC 95%: –9,45-[–2,67]; p<0,001), contracción del nervio obturador (OR: 0,08; IC 95%: 0,02-0,34; p=0,03) y perforación de la vejiga (OR: 0,14; IC 95%: 0,06-0,36; p<0,001) y no hubo diferencias significativas en cuanto a la recurrencia a los 12meses (OR: 0,79; IC 95%: 0,61-1,04: p=0,09), tiempo quirúrgico (DM: 0,67; IC 95%: –1,92-3,25; p=0,61) y estenosis uretral (OR: 0,46; IC 95%: 0,14-1,47; p=0,19) en comparación con la resección transuretral convencional para sujetos con cáncer de vejiga primario no invasivo...(AU)

Introduction We performed a meta-analysis to evaluate the effect of en-bloc transurethral resection vs. conventional transurethral resection for primary non-muscle invasive bladder cancer. Methods A systematic literature search up to January 2022 was done and 28 studies included 3714 primary non-muscle invasive bladder cancer subjects at the start of the study; 1870 of them were en-bloc transurethral resection, and 1844 were conventional transurethral resection for primary non-muscle invasive bladder cancer. We calculated the odds-ratio (OR) and mean-difference (MD) with 95% confidence-intervals (CIs) to evaluate the effect of en-bloc transurethral resection compared with conventional transurethral resection for primary non-muscle invasive bladder cancer by the dichotomous or continuous methods with random or fixed-effects models. Results En-bloc transurethral resection had significantly lower twenty-four-month recurrence (OR: 0.63; 95%CI: 0.50-0.78; P<0.001), catheterization-time (MD: –0.66; 95%CI: –1.02-[–0.29]; P<0.001), length of hospital stay (MD: –0.95; 95%CI: –1.55-[–0.34]; P=0.002), postoperative bladder irrigation duration (MD: –6.06; 95%CI: –9.45-[–2.67]; P<0.001), obturator nerve reflex (OR: 0.08; 95%CI: 0.02-0.34; P=0.03), and bladder perforation (OR: 0.14; 95%CI: 0.06-0.36: P<0.001) and no significant difference in the 12-month-recurrence (OR: 0.79; 95%CI: 0.61-1.04; P=0.09), the operation time (MD: 0.67; 95%CI: –1.92-3.25; P=0.61), and urethral stricture (OR: 0.46; 95%CI: 0.14-1.47; P=0.19) compared with conventional transurethral resection for primary non-muscle invasive bladder cancer subjects... (AU)

[Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 µmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3ß (p-GSK3ß) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 µmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3ß were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

[Lysosomal membrane protein Sidt2 knockout induces apoptosis of human hepatocytes in vitro independent of the autophagy-lysosomal pathway].

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 µmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells. CONCLUSION: Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.

[Comparison of therapeutic effect of metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus in obese patients].

OBJECTIVE: To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients. METHODS: We retrospectively collected the clinical data of 107 obese patients (BMI>25 kg/m2) with T2DM treated in Second Affiliated Hospital of Wannan Medical College (Wuhu, China) during 2019-2021, including 53 patients treated continuously with metformin hydrochloride/vildagliptin and 54 with liraglutide for 3 months. The changes in BMI, waist circumference, fasting blood glucose (FBG), postprandial blood glucose, HbA1C, fasting C-peptide, postprandial C-peptide, fasting insulin and postprandial insulin of the patients after treatment were compared between the two groups. RESULTS: In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all P < 0.05) with improved fasting and postprandial C-peptide levels after the treatments (P < 0.05). The two treatment regimens showed comparable blood glucoselowering effects, but liraglutide produced better effect in reducing waist circumference (P < 0.01). Neither of two regimens obviously affected insulin level of the patients (P>0.05). CONCLUSION: Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

Quantifying the effectiveness of ultraviolet-C light at inactivating airborne Mycobacterium abscessus.

BACKGROUND: Mycobacterium abscessus (MABS) group are environmental organisms that can cause infection in people with cystic fibrosis (CF) and other suppurative lung diseases. There is potential for person-to-person airborne transmission of MABS among people with CF attending the same care centre. Ultraviolet light (band C, UV-C) is used for Mycobacterium tuberculosis control indoors; however, no studies have assessed UV-C for airborne MABS. AIM: To determine whether a range of UV-C doses increased the inactivation of airborne MABS, compared with no-UVC conditions. METHODS: MABS was generated by a vibrating mesh nebulizer located within a 400 L rotating drum sampler, and then exposed to an array of 265 nm UV-C light-emitting diodes (LED). A six-stage Andersen Cascade Impactor was used to collect aerosols. Standard microbiological protocols were used for enumerating MABS, and these quantified the effectiveness of UV-C doses (in triplicate). UV-C effectiveness was estimated using the difference between inactivation with and without UV-C. FINDINGS: Sixteen tests were performed, with UV-C doses ranging from 276 to 1104 µW s/cm2. Mean (±SD) UV-C effectiveness ranged from 47.1% (±13.4) to 83.6% (±3.3). UV-C led to significantly greater inactivation of MABS (all P-values ≤0.045) than natural decay at all doses assessed. Using an indoor model of the hospital environment, it was estimated that UV-C doses in the range studied here could be safely delivered in clinical settings where patients and staff are present. CONCLUSION: This study provides empirical in-vitro evidence that nebulized MABS are susceptible to UV-C inactivation.

En-bloc transurethral resection vs. conventional transurethral resection for primary non-muscle invasive bladder cancer: A meta-analysis.

INTRODUCTION: We performed a meta-analysis to evaluate the effect of en-bloc transurethral resection vs. conventional transurethral resection for primary non-muscle invasive bladder cancer. METHODS: A systematic literature search up to January 2022 was done and 28 studies included 3714 primary non-muscle invasive bladder cancer subjects at the start of the study; 1870 of them were en-bloc transurethral resection, and 1844 were conventional transurethral resection for primary non-muscle invasive bladder cancer. We calculated the odds-ratio (OR) and mean-difference (MD) with 95% confidence-intervals (CIs) to evaluate the effect of en-bloc transurethral resection compared with conventional transurethral resection for primary non-muscle invasive bladder cancer by the dichotomous or continuous methods with random or fixed-effects models. RESULTS: En-bloc transurethral resection had significantly lower twenty-four-month recurrence (OR: 0.63; 95%CI: 0.50-0.78; p < 0.001), catheterization-time (MD: -0.66; 95%CI: -1.02-[-0.29]; p < 0.001), length of hospital stay (MD: -0.95; 95%CI: -1.55-[-0.34]; p = 0.002), postoperative bladder irrigation duration (MD: -6.06; 95%CI: -9.45-[-2.67]; p < 0.001), obturator nerve reflex (OR: 0.08; 95%CI: 0.02-0.34; p = 0.03), and bladder perforation (OR: 0.14; 95%CI: 0.06-0.36: p < 0.001) and no significant difference in the 12-month-recurrence (OR: 0.79; 95%CI: 0.61-1.04; p = 0.09), the operation time (MD: 0.67; 95%CI: -1.92 to 3.25; p = 0.61), and urethral stricture (OR: 0.46; 95%CI: 0.14-1.47; p = 0.0.19) compared with conventional transurethral resection for primary non-muscle invasive bladder cancer subjects. CONCLUSIONS: En-bloc transurethral resection had a significantly lower twenty-four-month recurrence, catheterization time, length of hospital stay, postoperative bladder irrigation duration, obturator nerve reflex, bladder perforation, and no significant difference in the twelve-month recurrence, operation time, and urethral stricture compared with conventional transurethral resection for primary non-muscle invasive bladder cancer subjects. Further studies are required.

[Efficacy observation and compliance analysis of pollen allergen drops in seasonal allergic rhinitis].

To study the efficacy and compliance analysis of pollen allergen drops in the treatment of allergic rhinitis. The method of single-center controlled was used to analyze the dates' results. From July 2021 to September 2021, 80 patients with seasonal allergic rhinitis were referred to the clinic of otorhinolaryngology in First Hospital of Shanxi Medical University.40 patients received sublingual immunotherapy (SLIT group), and the other 40 patients received symptomatic drug treatment as the control group. The total rhinoconjunctivitis symptom score (TRSS), the visual analogue scale(VAS), total medication score (TMS) and combined scores of medication and rhinoconjunctivitis symptoms (CSMRS) of the patient before the start of the treatment and after the first year of the treatment were compared to assess the efficacy of sublingual immunotherapy of Artemisia pollen. Follow the shedding during the study, the safety of the drug and the causes for compliance analysis were analyzed and recorded. The results of comparison with TRSS, VAS, TMS and CSMRS in two groups in the period of pretherapy were as follows: TRSS(12.393±3.023, 12.450±3.029, t=-0.077, P=0.939), VAS(8.357±1.026, 8.400±0.982, t=-0.173, P=0.862), TMS(3.214±0.568, 3.175±0.501, t=0.301, P=0.764), CSMRS (5.286±0.680, 5.253±0.677, t=0.199, P=0.843), there was no significant difference (P>0.05); lower observed symptom scores were got in the post-treatment pollen peak SLIT group compared to the control group, TRSS(3.964±1.551, 7.750±2.169, t=-7.918, P<0.05), VAS(2.893±0.956, 5.175±1.481, t=-8.286, P<0.05), TMS (1.821±0.863, 3.175±0.501, t=-8.163, P<0.05), CSMRS (2.489±0.921, 4.468±0.601, t=-10.723, P<0.05), and the differences between the groups were statistically significant (P<0.05); the SLIT group significantly reduced all symptom scores at the first peak compared to the starting, TRSS(12.393±3.023, 3.964±1.551, t=20.576, P<0.05), VAS (8.357±1.026, 2.893±0.956, t=30.070, P<0.05), TMS (3.214±0.568, 1.821±0.863, t=7.151, P<0.05), CSMRS(5.286±0.680, 2.489±0.921, t=14.533, P<0.05) and there was statistical difference (P<0.05). No significant adverse reactions occured during medication in the SLIT group. A total of 12 cases were shed in the SLIT group, so the compliance rate was 70%. The four reasons were that patients considered the course was long (4 cases, 33%); the drugs were expensive (3 cases, 25%); patients were busy with their work and life (3 cases, 25%); patients were affected by the outbreak (2 cases, 17%). In summary, Artemisia pollen sublingual drops may improve the symptoms of the patients who got allergic rhinitis caused by Artemisia pollen after the treatment for one year. However, due to the lack of sufficient understanding of immunotherapy or the difficulty in adhering to standardized medication, the compliance with sublingual immunotherapy is still poor, the compliance with sublingual immunotherapy needs to be further improved through patient education.

Structural Determination of Lysine-Linked Cisplatin Complexes via IRMPD Action Spectroscopy: NNs and NO- Binding Modes of Lysine to Platinum Coexist.

Despite its success as an anticancer drug, cisplatin suffers from resistance and produces side effects. To overcome these limitations, amino-acid-linked cisplatin analogues have been investigated. Lysine-linked cisplatin, Lysplatin, (Lys)PtCl2, exhibited outstanding reactivity toward DNA and RNA that differs from that of cisplatin. To gain insight into its differing reactivity, the structure of Lysplatin is examined here using infrared multiple photon dissociation (IRMPD) action spectroscopy. To probe the influence of the local chemical environment on structure, the deprotonated and sodium-cationized Lysplatin complexes are examined. Electronic structure calculations are performed to explore possible modes of binding of Lys to Pt, their relative stabilities, and to predict their infrared spectra. Comparisons of the measured IRMPD and predicted IR spectra elucidate the structures contributing to the experimental spectra. Coexistence of two modes of binding of Lys to Pt is found where Lys binds via the backbone and side-chain amino nitrogen atoms, NNs, or to the backbone amino and carboxylate oxygen atoms, NO-. Glycine-linked cisplatin and arginine-linked cisplatin complexes have previously been found to bind only via the NO- binding mode. Present results suggest that the NNs binding conformers may be key to the outstanding reactivity of Lysplatin toward DNA and RNA.

[Proliferative lesions with mesonephric features in the gynecologic tract: a clinicopathological analysis of sixteen cases].

Objective: To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. Methods: A retrospective analysis was performed on the clinical and pathological data of 16 cases with PMF that were diagnosed from October 2016 to January 2022 at a single institution. The relevant literature was reviewed. Results: Among the 16 cases, with an average of 53 years (31-68 years), there were 5 cases of mesonephric hyperplasia, 4 cases of mesonephric adenocarcinoma and 7 cases of mesonephric-like adenocarcinoma. The five cases of mesonephric hyperplasia were located in the lateral wall of the cervix and composed of simple tubules with growth patterns of diffuse or lobular clusters, without obvious stromal reaction. Four cases of mesonephric adenocarcinoma consisted of a mixture of papillary, cribriform, solid and other architectures, the nuclei resembling these of papillary thyroid carcinoma, and strong fibroproliferative reaction. They were located deep in the cervical and vaginal stroma. One of the tumors showed atypical mesonephric hyperplasia adjacent to the tumor. Five uterine and two ovarian mesonephric-like adenocarcinoma cases had similar histological morphology with mesonephric adenocarcinoma, but no mesonephric remnants/mesonephric hyperplasia were found near the tumors. In addition, four (4/5) uterine mesonephric-like adenocarcinoma cases originated from the endometrium with secondary involvement of myometrium, including one case with clear demarcation between the normal endometrium and the neoplastic glands. One (1/5) uterine mesonephric-like adenocarcinoma case was mainly located in the deep myometrium, along with adenomyosis around the tumor, without mesonephric remnants. Two ovarian mesonephric-like adenocarcinoma cases were associated with endometriotic cyst/endometrioid cystadenoma, including one case with an abrupt transition between normal epithelium and atypical mesonephric cells within the single individual cyst directly adjacent to tumor. All mesonephric hyperplasia and mesonephric adenocarcinoma cases were positive for GATA3, PAX8 and CD10 in a varying degree, and negative for ER, PR and TTF1. Although mesonephric-like adenocarcinoma showed a considerable overlap of immunohistochemical expression with mesonephric adenocarcinoma, seven mesonephric-like adenocarcinoma cases were positive for TTF1 and negative for GATA3. Conclusions: PMF is a class of rare proliferative lesions with morphological and immunophenotypic characteristics of mesonephric duct. Its commonly involved site, microscopic morphology, associated benign and/or atypical lesions, and immunophenotype may contribute to its diagnosis and differential diagnosis.