Influence of Solvent Selection on the Crystallizability and Polymorphic Selectivity Associated with the Formation of the "Disappeared" Form I Polymorph of Ritonavir.

The comparative crystallizability and polymorphic selectivity of ritonavir, a novel protease inhibitor for the treatment of acquired immune-deficiency syndrome, as a function of solvent selection are examined through an integrated and self-consistent experimental and computational molecular modeling study. Recrystallization at high supersaturation by rapid cooling at 283.15 K is found to produce the metastable "disappeared" polymorphic form I from acetone, ethyl acetate, acetonitrile, and toluene solutions in contrast to ethanol which produces the stable form II. Concomitant crystallization of the other known solid forms is not found under these conditions. Isothermal crystallization studies using turbidometric detection based upon classical nucleation theory reveal that, for an equal induction time, the required driving force needed to initiate solution nucleation decreases with solubility in the order of ethanol, acetone, acetonitrile, ethyl acetate, and toluene consistent with the expected desolvation behavior predicted from the calculated solute solvation free energies. Molecular dynamics simulations of the molecular and intermolecular chemistry reveal the presence of conformational interplay between intramolecular and intermolecular interactions within the solution phase. These encompass the solvent-dependent formation of intramolecular O-H...O hydrogen bonding between the hydroxyl and carbamate groups coupled with differing conformations of the hydroxyl's shielding phenyl groups. These conformational preferences and their relative interaction propensities, as a function of solvent selection, may play a rate-limiting role in the crystallization behavior by not only inhibiting to different degrees the nucleation process but also restricting the assembly of the optimal intermolecular hydrogen bonding network needed for the formation of the stable form II polymorph.

Shear wave propagation in a liquid crystal: An inelastic X-ray scattering study.

We investigated the spectrum of density fluctuations of a liquid crystal, CB7CB, in two different orientations by using high-resolution inelastic x-ray scattering. Our analysis, based on Bayesian principles, revealed that high-frequency collective excitations propagate through this mesoscale-ordered sample in a peculiar manner that lies somewhere between those observed in liquids and crystalline systems. Interestingly, when we probed longer length scales, a more pronounced solid-like response emerged. This was mainly characterized by anomalously sharp inelastic excitations and the onset of shear mode propagation. Comparison with previous x-ray diffraction results suggests a correlation between the observed behavior and the mesogen arrangement.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

Gut microbiota, a potential cause of higher insulin sensitivity in children with Prader-Willi syndrome.

PURPOSE: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls. METHODS: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples. RESULTS: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR. CONCLUSION: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.

Effects of nondigestible oligosaccharides on inflammation, lung health, and performance of calves.

Our objective was to determine the effects of nondigestible oligosaccharides (NDO) on lung health and performance. Three hundred male Holstein-Friesian calves aged 18.0 ± 3.6 d received 1 of 6 treatments for 8.5 wk (period 1). Treatments included a negative control (CON), galacto-oligosaccharides (GOS) administered as a spray via the nose once daily (SPR), GOS administered via the milk replacer (MR) at 1% (GOS-L) and 2% (GOS-H), fructo-oligosaccharides administered via the MR at 0.25% (FOS) and a combination of GOS and fructo-oligosaccharides administered via the MR at 1% and 0.25%, respectively (GOS-FOS). Milk replacer was fed twice daily. Feeding levels were equal between calves and increased progressively in time. Body weight was measured every 4 wk and clinical health was scored weekly. Blood and broncho-alveolar lavage fluid (BALF) samples were collected bi-weekly from a subset of calves (n = 120). After period 1, all calves received the same control MR for 18 wk until slaughter (period 2), during which general performance and clinical health were measured. Generally, infection pressure was high, with clinical scores and BALF proinflammatory TNFα concentrations increasing with time in period 1, which resulted in a high number of required group antimicrobial treatments (6 group antimicrobial treatments in 13 wk, supplied to all calves). Average daily gain adjusted to equal solid feed intake was increased for GOS-L (+61 g/d) compared with CON calves from experimental wk 1 to 5. Plasma white blood cell concentration tended to be lowered by GOS-L, plasma IL-8 concentration was reduced by all orally supplemented NDO, plasma IL-6 was reduced by all NDO treatments except GOS-FOS and plasma IL-1ß was reduced by all NDO treatments compared with CON, although this differed per time point for SPR. The neutrophil percentage in BALF was reduced by GOS-L in wk 6, which was associated with a relative increase in macrophages. The BALF concentration of TNFα and IL-8 was reduced or tended to be reduced by GOS-L and GOS-H, while IL-6 was or tended to be reduced by SPR, GOS-L, GOS-H, and GOS-FOS, and IL-1ß was reduced by SPR, GOS-L, GOS-H, and FOS. Generally, feeding the combination of GOS and FOS was not more effective than feeding GOS or FOS alone, because feeding GOS-FOS resulted in higher concentrations of plasma and BALF cytokine and chemokine concentrations compared with feeding GOS-L alone, and resulted in higher plasma cytokine concentrations compared with feeding FOS alone. None of the BALF and plasma cytokine or chemokine concentrations differed between the GOS-L and GOS-H treatment. Performance and clinical scores in period 2 did not differ among treatments. Altogether, all tested NDO reduced systemic and lung inflammation in calves under high natural infection pressure and for GOS-fed calves, this increased performance during the first 4 wk. Combining GOS and FOS did not have a synergistic effect. The intranasal administration of GOS also lowered systemic and lung inflammation, but tended to negatively affect performance. Overall, this study demonstrates the potential of NDO to alleviate systemic and respiratory inflammation in calves.

[Safety and efficacy of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis].

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant (P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation (P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups (P>0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Spontaneous bone regeneration in segmental mandibular defects: A systematic review.

BACKGROUND: Rehabilitation for segmental mandibular defect is vital for mastication function and facial aesthetics. Interestingly spontaneous bone regeneration after segmental mandibulectomy sporadically occurs to avoid further bony rehabilitation. This study aimed to assess the potential of spontaneous bone regeneration in the treatment of mandibular defects. MATERIAL AND METHODS: An electronic search was conducted using the PubMed, EMBASE, Wiley Online Library, and Cochrane Library databases to identify eligible studies. Critical appraisal of the included articles was done using the Joanna Briggs Institute critical appraisal checklist. RESULTS: A total of 35 studies, including 60 patients, that investigated spontaneous bone regeneration after segmental mandibulectomy were included. Among these patients, 39 (65%) were male and 21 (35%) were female, with a mean age of 20.81 ± 16.38 years. Periosteum was completely and partially preserved during mandibulectomy in 25 and 13 patients, respectively. Continuous bone regeneration between mandibular stumps was observed in 53 (88.3%) patients during follow-up. Although the mandibular stump was not stabilized in 13 (21.67%) patients, continuous bony regeneration still occurred, with a mean recovery period of 30.29 months. This was significantly greater than the overall average recovery time of 19.87 months. CONCLUSIONS: Spontaneous bone regeneration could occur in segmental mandibular defects, particularly in young patients with intact periosteum and rigid mandibular stump fixation.

[The association between frontotemporal connecting fibers and seizure severity in patients with temporal lobe epilepsy].

The patients with temporal lobe epilepsy (TLE) admitted in the Department of Neurology, Zhongshan Hospital, Fudan University from June 2009 to February 2012 were prospectively enrolled. The diffusion tensor imaing was performed on the patients at the time of enrollment and 3 years later. The fractional anisotropy (FA) values of the white matter connecting fibers(bilateral hooked, arcuate, cingulate, and superior longitudinal tracts), the connecting fibers of both hemispheres(anterior union, anterior callosal forceps, posterior forceps, and bilateral fornix), and fibers of perirhinal cortices system(bilateral radiating crown and anterior limb of the internal capsule) were measured by the region of interest method. The severity of epilepsy was evaluated using the Veterans Administration Seizure Type and Frequency Rating Scale(VA-2) and National Hospital Seizure Severity Scale (NHS3). A total of 51 patients with TLE were screened, with 27 patients completing the 3-year follow-up. There were 13 males and 14 females with an age of (32±11) years and a follow-up duration of (39.1±1.1) months. During the follow-up, 6 patients had increased/unchanged NHS3 or VA-2 scores, while 21 patients had decreased scores. Three years later, the FA values of the bilateral arcuate fasciculus, the right superior longitudinal fasciculus, the right radial coronal and corpus callosum anterior forceps in TLE patients decreased compared to baseline(P<0.05). However, compared to the patients with decreased VA-2 scores during the follow-up, the degree of increase in FA values (ΔFA, follow-up FA value-baseline FA value) of the ipsilateral hook bundle caused by epilepsy was more significant in the group with increased/unchanged VA-2 scores (decreased score group vs increased/unchanged score group:-0.032±0.063 vs 0.018±0.043, t=2.305, P=0.035). The value of ΔFA in epileptic patients with increased/unchanged NHS3 scores (0.075±0.113) was higher compared to those with decreased scores (-0.079±0.099, t=2.804, P=0.010). Correlation analysis also showed the changes in FA values of epileptic lateral fasciculus (r=0.503, P=0.009) and arcuate fasciculus (r=0.602, P=0.001)were positively correlated with the changes in VA-2 and HNS3 scores, respectively. The seizure severity in patients with TLE was closely associated with the microstructure changes in the frontal and temporal white matter, especially the arcuate and uncinate tracts, on the same side that caused seizures, which may indicate the white matter remodeling and abnormal network reformation associated with seizures.

[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

[Research advances on the mechanism of immune regulation of interferon in Aspergillus infection].

Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in Aspergillus infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in Aspergillus infections.

[Intervention of traditional Chinese patent medicine based on syndrome differentiation in female patients after percutaneous coronary intervention due to acute coronary syndrome: a nationwide multicenter prospective cohort study].

Objective: To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Methods: The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis. Results: A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95%CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95%CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint (HR=0.62,95%CI 0.40-0.97,P=0.033) and second endpoint (HR=0.56, 95%CI 0.37-0.87,P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion: On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Predicting the Strength of Cohesive and Adhesive Interparticle Interactions for Dry Powder Inhalation Blends of Terbutaline Sulfate with α-Lactose Monohydrate.

Grid-based systematic search methods are used to investigate molecule-molecule, molecule-surface, and surface-surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle-particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS-TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH-LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). METHODS: A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). RESULTS: The mean age of the enrolled participants was 44.35 years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [- 16.42 (- 22.18, - 10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67 µg, Log2-transformed). CONCLUSION: Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

[Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma].

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.

[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[Analysis of the international application of healthy life expectancy].

Healthy life expectancy is based on life expectancy to further identify the healthy component, moving the assessment threshold from the mortality to the whole life cycle, receiving more and more attention worldwide. Nowadays, it has become one of the core indicators of national major strategy and plan. As a comprehensive indicator of health measurement, healthy life expectancy is complicated and multi-dimensional. Different social and cultural backgrounds have different understandings of health and choose different measurement dimensions. Overall, although high-income countries have different choices in their national health plan, healthy life expectancy without activity restriction is by far the most widely used indicator. This paper reviewed the concept and application of healthy life expectancy systematically, drawing on international practical experience to provide reference for the establishment of a healthy life expectancy indicator system in line with the Chinese national conditions.

[A prospective study of position selection combined with autologous blood intrathoracic infusion in the treatment of postoperative persistent air leakage with an unexpanded lung].

We prospectively studied 17 patients with spontaneous pneumothorax or giant emphysematous bulla at Rizhao Hospital of Traditional Chinese Medicine from October 2020 to March 2022. All patients underwent thoracoscopic interventional therapy, had experienced continued air leakage for 3 days with closed thoracic drainage postoperatively, had an unexpanded lung on CT, and/or failed to intervention with position selection combined with intra-pleural thrombin injection(referred to as "position plus1.0"). They were all treated with position selection combined with autologous blood (100 ml) and thrombin (5 000 U) intra-pleural injection(referred to as "position plus 2.0").The success rate of the "position plus 2.0" intervention was 16/17, and the recurrence rate was 3/17. There were four cases of fever, four cases of pleural effusion, one case of empyema, and no other adverse reactions. This study has shown that the "position plus 2.0" intervention is safe, effective, and simple for patient with persistent air leakage failed to intervention with"position plus 1.0" after thoracoscopic treatment of pulmonary and pleural diseases related to bulla.

[The mechanism of OC-STAMP overexpression induced actin cytoskeleton remodeling in promoting epithelial-mesenchymal transition in the alveolar type â ¡ epithelial cell].

Objective: To explore the mechanism of osteoclast stimulatory transmembrane protein (OC-STAMP) overexpression on epithelial-mesenchymal transition (EMT) . Methods: In April 2021, mice alveolar type Ⅱ epithelial cells MLE-12 were divided into five groups: overexpression control group (NC group), Ocstamp overexpression group (over-Ocstamp group), Fasudil intervention group (over-Ocstamp+Fasudil group), silence control group (si-NC group), Ocstamp silence group (si-Ocstamp group). The protein expressions of OC-STAMP, epithelial marker protein-E-cadherin (E-cad), interstitial marker protein-α-smooth muscle actin (α-SMA), Ras homolog gene family member A (RhoA), Rho GDP dissociation inhibitor α (Rho GDIα), Rho-associated protein kinase (ROCK), phosphate myosin phosphatase (p-MYPT) were examined by Western blotting and Immunocytochemical staining. The filamentous actin (F-actin) was detected by Phalloidin method. t test was used to compare the relative expression of each protein between the two groups. Results: Western blotting and Immunocytochemical staining showed that compared with the NC group, the expression level of E-cad was down-regulated, while the expression levels of α-SMA, Rho GDIα, RhoA, ROCK, p-MYPT were increased, and F-actin expression was enhanced in the over-Ocstamp group. The differences were statistically significant (P<0.05). There were no significant differences in E-cad and α-SMA protein expression in si-Ocstamp group compared with si-NC group (P>0.05). Compared with over-Ocstamp group, the expression level of E-cad protein in over-Ocstamp+Fasudil group was up-regulated, the expression levels of α-SMA, Rho GDIα, RhoA, ROCK and p-MYPT protein were decreased, and F-actin expression was weakened, with statistical significance (P<0.05) . Conclusion: OC-STAMP overexpression in alveolar type Ⅱ epithelial cells may induce actin cytoskeleton remodeling through activation of Rho GDIα/RhoA/ROCK signaling pathway, thus promoting EMT.

Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.

OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.

Characterizing seasonal transitions: Breeding-like morphology and behavior during the late non-breeding season in green anole lizards.

Seasonally breeding animals, such as green anole lizards (Anolis carolinensis), allow for the examination of the control of reproduction during different reproductive states. During the breeding season, the gonads are large and reproductively active. Following the breeding season, gonads regress and become less active, and the lizards enter a refractory period where breeding is inhibited. After this stage, a post-refractory period occurs during which the lizards are still in a non-breeding state, but environmental changes can trigger the onset of breeding. However, it is unclear what causes these changes in reproductive state and we hypothesized that this may be due to alterations in gonadotropin-releasing hormone (GnRH) signaling. The present study aimed to identify morphological and behavioral differences in GnRH- and saline-injected refractory and post-refractory male anoles when housed under the same non-breeding environmental conditions. We found that post-refractory anoles had increased testicular weight, recrudescence, sperm presence, and reproductive behavior, with no impact of GnRH injection. Renal sex segment size and steroidogenic acute regulatory protein (StAR) mRNA levels did not differ among groups, indicating that testosterone levels likely had not increased in post-refractory lizards. Post-refractory anoles in this study were beginning to transition towards a breeding state without exposure to changing environmental conditions, and GnRH was not necessary for these changes. These data reveal a complex interaction between the activation of breeding, changing environmental conditions, and the underlying physiology regulating reproduction in seasonally breeding lizards. Future studies are needed to further elucidate the mechanisms that regulate this relationship.