The association between leptin and diabetes: A meta-analysis.

PURPOSE: The study object was to determine the relationship between leptin and diabetes. METHODS: We searched for the literature on the relationship between leptin and diabetes from PubMed, EMBASE, Cochrane Library, and CNKI databases. We carried out the meta-analysis by calculating the Std. Mean Difference (SMD) and 95% confidence intervals (CIs) to study the relationship between leptin and diabetes. We performed the Chi-square-based Q test and I2 statistics to evaluate the potential heterogeneity, and the sensitivity analysis was performed to evaluate the stability of our results. Moreover, Begg's test was performed to evaluate the publication bias. RESULTS: There are 10 studies in this study for meta-analysis, which include 1879 patients (diabetic (n = 1024); and nondiabetic patients (n = 855)). The results indicated that the levels of serum leptin were significantly increased in patients with diabetes (SMD = 1.78, 95% CI [0.81, 2.76]), especially those with gestational diabetes mellitus compared with controls (SMD = 3.03, 95% CI [1.21, 4.86]). However, the results showed that there was no difference in serum leptin levels between type 2 diabetes and controls (SMD = 0.34, 95% CI [-1.06, 1.74]). CONCLUSIONS: Our analysis indicated that the levels of serum leptin were significantly elevated in patients with diabetes especially those with gestational diabetes mellitus compared with controls.

Self-Assembled Microfiber-Like Biohydrogel for Ultrasensitive Whole-Cell Electrochemical Biosensing in Microdroplets.

A novel microfiber-like biohydrogel was fabricated by a facile approach relying on electroactive bacteria-induced graphene oxide reduction and confined self-assembly in a capillary tube. The microfiber-like biohydrogel (d = ∼1 mm) embedded high-density living cells and activated efficient electron exchange between cells and the conductive graphene network. Further, a miniature whole-cell electrochemical biosensing system was developed and applied for fumarate detection under -0.6 V (vs Ag/AgCl) applied potential. Taking advantage of its small size, high local cell density, and excellent electron exchange, this microfiber-like biohydrogel-based sensing system reached a linear calibration curve (R2 = 0.999) ranging from 1 nM to 10 mM. The limit of detection obtained was 0.60 nM, which was over 1300 times lower than a traditional biosensor for fumarate detection in 0.2 µL microdroplets. This work opened a new dimension for miniature whole-cell electrochemical sensing system design, which provided the possibility for bioelectrochemical detection in small volumes or three-dimensional local detection at high spatial resolutions.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.

Pyroptosis, a target for cancer treatment?

Pyroptosis is a newly discovered form of programmed cell death mediated by the gasdermin protein, that is accompanied by inflammation and immune response. A growing body of evidence suggests that pyroptosis is closely related to cancer, and it is becoming a new cancer research topic. Studies have suggested that different cancer cells activate pyroptosis in different ways and that the effects of pyroptosis vary in different cancer backgrounds. In this article, we briefly introduce the definition, characteristics, and activation pathways of pyroptosis. Then we review the complex effects of pyroptosis on cancer development, which generally include inhibition of cancer cell viability, impacts on the invasion and migration of cancer cells, improvement of antitumor immunity, and enhancement of chemotherapy sensitivity. We also discuss drugs and compounds that can induce pyroptosis, as well as the interaction between pyroptosis and apoptosis. Elucidating the mechanisms of the complex effects of pyroptosis is likely to pave the way for therapeutic approaches for cancer in the future.

A Decade of Scientific and Technological Innovation at Chinese Academy of Medical Sciences & Peking Union Medical College: Retrospect and Prospect.

Focusing on the reform initiatives of Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC) in medical scientific and technological innovation from perspectives of deepening the reform and optimizing the ecosystem of science and technology innovation, this article summarizes the highlights of CAMS & PUMC's efforts in safeguarding people's health and promoting the Healthy China 2030 strategy through scientific and technological innovation in the fields including basic research, disease prevention and treatment, and medical technology in the past ten years. These achievements embody the endeavors and responsibility of CAMS & PUMC in realizing self-reliance and self-improvement of Chinese medical science and technology and highlight its contributions to the development of medical science and technology of China.

[6-Gingerol ameliorates adipose tissue insulin resistance in aging rats].

This study investigated the effects and mechanisms of 6-gingerol on adipose tissue insulin resistance in naturally aging rats with glycolipid metabolism disorders. Twenty-seven aging male SD rats were randomly divided into a model group(aged, n=9) and two groups treated with 6-gingerol at 0.05 mg·kg~(-1)(G-L, n=9) and 0.2 mg·kg~(-1)(G-H, n=9). Six young rats were randomly assigned to a normal control group(NC). Rats were treated for seven weeks by gavage. Non-esterified fatty acid(NEFA) and insulin content was determined by enzyme-linked immunosorbent assay(ELISA), and adipose tissue insulin resistance index(Adipo-IR) was calculated. HE staining was used to observe the size of adipocytes in epididymal white adipose tissue(eWAT). The gene and protein expression levels of adiponectin receptor 1(AdipoR1), AMP-activated protein kinase α(AMPKα), phosphorylated AMPK(p-AMPKα~(Thr172)), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), phosphorylated Akt(p-Akt~(Ser473)), tumor necrosis factor-α(TNF-α), c-Jun N-terminal kinase 1/2(JNK1/2), phosphorylated JNK1/2(p-JNK~(Thr183/Tyr185)), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) in adiponectin(APN), insulin, and inflammatory factor signaling pathways were detected by Western blot and real-time RCR, respectively. The results showed that 6-gingerol at a high dose could significantly decrease the fasting plasma content of NEFA and insulin and reduce Adipo-IR. Additionally, 6-gingerol at a high dose significantly increased the protein and mRNA expression of APN, AdipoR1, PGC-1α, and PI3 K in eWAT, elevated the relative expression of p-AMPK~(Thr172) and p-Akt~(Ser 473), reduced the protein and mRNA expression of TNF-α, IL-1, and IL-6 in eWAT, and decreased the relative expression of p-JNK1 and p-JNK2. This study reveals that 6-gingerol can improve insulin sensitivity of adipose tissues in aging rats with glycolipid metabolism disorders, and this effect is presumedly achieved by enhancing the PI3 K/Akt signaling pathway, inhibiting adipose tissue inflammation, increasing APN synthesis, enhancing AdipoR1 expression, and activating its downstream AMPK/PGC-1α signaling pathway.

CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1.

BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. METHODS: shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. RESULTS: We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. CONCLUSION: In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

Proposing a deep learning-based method for improving the diagnostic certainty of pulmonary nodules in CT scan of chest.

OBJECTIVE: To compare the performance of a deep learning (DL)-based method for diagnosing pulmonary nodules compared with radiologists' diagnostic approach in computed tomography (CT) of the chest. MATERIALS AND METHODS: A total of 150 pathologically confirmed pulmonary nodules (60% malignant) assessed and reported by radiologists were included. CT images were processed by the proposed DL-based method to generate the probability of malignancy (0-100%), and the nodules were divided into the groups of benign (0-39.9%), indeterminate (40.0-59.9%), and malignant (60.0-100%). Taking the pathological results as the gold standard, we compared the diagnostic performance of the proposed DL-based method with the radiologists' diagnostic approach using the McNemar-Bowker test. RESULTS: There was a statistically significant difference between the diagnosis results of the proposed DL-based method and the radiologists' diagnostic approach (p < 0.001). Moreover, there was no statistically significant difference in the composition of the diagnosis results between the proposed DL-based method and the radiologists' diagnostic approach (all p > 0.05). The difference in diagnostic accuracy between the proposed DL-based method (70%) and radiologists' diagnostic performance (64%) was not statistically significant (p = 0.243). CONCLUSIONS: The proposed DL-based method achieved an accuracy comparable with the radiologists' diagnostic approach in clinical practice. Furthermore, its advantage in improving diagnostic certainty may raise the radiologists' confidence in diagnosing pulmonary nodules and may help clinical management. Therefore, the proposed DL-based method showed great potential in a certain clinical application. KEY POINTS: • Deep learning-based method for diagnosing the pulmonary nodules in computed tomography provides a higher diagnostic certainty.

Natural history of pathologically confirmed pulmonary subsolid nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To explore the natural history of pulmonary subsolid nodules (SSNs) with different pathological types by deep learning-assisted nodule segmentation. METHODS: Between June 2012 and June 2019, 95 resected SSNs with preoperative long-term follow-up were enrolled in this retrospective study. SSN detection and segmentation were performed on preoperative follow-up CTs using the deep learning-based Dr. Wise system. SSNs were categorized into invasive adenocarcinoma (IAC, n = 47) and non-IAC (n = 48) groups; according to the interval change during the preoperative follow-up, SSNs were divided into growth (n = 68), nongrowth (n = 22), and new emergence (n = 5) groups. We analyzed the cumulative percentages and pattern of SSN growth and identified significant factors for IAC diagnosis and SSN growth. RESULTS: The mean preoperative follow-up was 42.1 ± 17.0 months. More SSNs showed growth or new emergence in the IAC than in the non-IAC group (89.4% vs. 64.6%, p = 0.009). Volume doubling time was non-significantly shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days, p = 0.077). Median mass doubling time was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). Lobulated sign (p = 0.002) and SSN mass (p = 0.004) were significant factors for differentiating IACs. IACs showed significantly higher cumulative growth percentages than non-IACs in the first 70 months of follow-up. The growth pattern of SSNs may conform to the exponential model. The initial volume (p = 0.042) was a predictor for SSN growth. CONCLUSIONS: IACs appearing as SSNs showed an indolent course. The mean growth rate was larger for IACs than for non-IACs. SSNs with larger initial volume are more likely to grow. KEY POINTS: • Invasive adenocarcinomas (IACs) appearing as subsolid nodules (SSNs), with a mean volume doubling time (VDT) of 1436.0 ± 1188.2 days and median mass doubling time (MDT) of 821.7 days, showed an indolent course. • The VDT was shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days), but the difference was not significant (p = 0.077). The median MDT was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). • SSNs with lobulated sign and larger mass (> 390.5 mg) may very likely be IACs. SSNs with larger initial volume are more likely to grow.

Joint Salvage and Biological Repair of Massive-Cavity Bone Defects After Extensive Curettage of Campanacci Grade II or III Giant Cell Tumor Around the Knee With Vascularized Fibular Autograft and Cancellous Allograft.

OBJECTIVE: The aim of the study was to report the clinical outcomes of repair of massive-cavity bone defects after extensive curettage of Campanacci grade II or III giant cell tumor (GCT) around knee with vascularized fibular autograft and cancellous allograft. METHODS: There were 12 consecutive patients with Campanacci grade II or III GCT around knee treated in our department between 2004 and 2016. All the patients underwent clinical evaluation, plain radiography, and/or magnetic resonance imaging of the knee right after admission. To preserve their knee function, we repaired the massive-cavity bone defects after extensive curettage of GCT by vascularized fibular autografts and cancellous allograft. All the patients were evaluated through clinical examinations, plain radiography of the knee and chest, and Musculoskeletal Tumor Society (MSTS) scores of the lower extremity in the follow-ups. RESULTS: The follow-up ranged from 1.5 to 12.0 years (mean, 4.2 years). There were no local recurrences or lung metastasis in any of the 12 patients at the last follow-up. Ten patients had no pain or experienced occasional pain, and 9 were able to resume their previous work. The mean range of motion of knee flexion was 117 degrees, and the extension was -6 degrees. The mean MSTS score was 24.7, and a total of 10 patients had excellent or good MSTS scores. CONCLUSIONS: It is reliable to achieve knee joint salvage and repair massive-cavity bone defects after extensive curettage with vascularized fibular autograft and cancellous allograft in patients with Campanacci grade II or III GCT around the knee.

Repair of Small-Size Wound With Achilles Tendon Exposure With Proximal Pedicled Cutaneous Neurovascular Flap.

OBJECTIVE: To investigate the clinical outcomes associated with repairing of small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap in the dorsolateral foot. METHODS: After thorough debridement, 16 cases with small-sized wounds of Achilles tendon exposure were repaired by proximal pedicled cutaneous neurovascular flap of the dorsolateral foot, and their clinical outcomes were observed. RESULTS: All the flaps in the 16 cases survived completely, excluding the marginal part necrosis in 1 case, and all the wounds were healed. The 2-point discrimination of the flaps was 14.53 ± 1.55 mm (range, 12-17 mm) in patients without sural nerve injury after 3 to 18 months follow-up. No discomfort was felt in wearing normal shoes by all the 16 patients. CONCLUSIONS: It is reasonable to repair the small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap of dorsolateral foot due to its effective repair of the wound, relatively uncomplicated surgery, and had satisfactory healing recovery.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

Structural Insights into the Host-Guest Complexation between ß-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives.

Understanding the host-guest chemistry of α-/ß-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used ß-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, ß-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests.

Evaluation of Contrast-enhanced US LI-RADS version 2017: Application on 2020 Liver Nodules in Patients with Hepatitis B Infection.

Background Use of contrast material-enhanced (CE) US Liver Imaging Reporting and Data System (LI-RADS) version 2017 has not been validated in large populations where hepatitis B virus (HBV) is endemic. Purpose To evaluate the diagnostic performance of CE US LI-RADS version 2017 in a population with a high prevalence of HBV infection. Materials and Methods In this retrospective study, liver nodules in patients with HBV who were evaluated from January 2004 to December 2016 were categorized as CE US LR-1 to LR-5 through LR-M. A subgroup of LR-M nodules was reclassified as LR-5, and additional analysis was performed. The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. Diagnostic performance was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results A total of 2020 nodules in 1826 patients (median age, 54 years ± 12 [standard deviation]; 1642 men) were included. Of the 1159 LR-5 lesions, 1141 were hepatocellular carcinoma (HCC); three, intrahepatic cholangiocarcinomas; six, other malignancies; six, atypical hyperplasia; and three, benign lesions. The PPV of LR-5 for HCC was 98% (95% confidence interval [CI]: 98%, 99%). In LR-M nodules, 153 showed arterial phase hyperenhancement, early washout, and absence of punched-out appearance within 5 minutes, and 142 of 153 (93%; 95% CI: 89%, 97%) were HCC. If these nodules were reclassified as LR-5, LR-M specificity and PPV as a predictor of non-HCC malignancy increased from 88% (95% CI: 87%, 89%) and 36% (95% CI: 31%, 41%) to 96% (95% CI: 95%, 97%) and 58% (95% CI: 51%, 65%), respectively (P < .001). Despite reclassification, LR-5 specificity and PPV remained high (94% [95% CI: 92%, 96%] and 98% [95% CI: 97%, 99%], respectively). Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System version 2017 category LR-5 is effectively predictive of the presence of hepatocellular carcinoma. In patients with hepatitis B virus infection, performance may be further improved by reclassification of category LR-M nodules with arterial phase hyperenhancement, early washout, and no punched-out appearance to LR-5. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sidhu in this issue.

Long-term follow-up of persistent pulmonary pure ground-glass nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning-assisted nodule segmentation. METHODS: Between January 2007 and October 2018, 110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth. RESULTS: The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8 months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339-8640) days, and their median MDT was 1332 (range, 290-38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p < 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (p = 0.044), initial mean diameter (p < 0.001), volume (p = 0.003), and mass (p = 0.023) predicted pGGN growth. CONCLUSIONS: Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow. KEY POINTS: • The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594). • The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448 days (range, 339-8640 days), and their median mass doubling time (MDT) was 1332 days (range, 290-38,912 days). The mean time to growth in volume was 854 ± 675 days (range, 116-2856 days). • The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.

Pseudomonas jilinensis sp. nov., Isolated from Oil Production Water of Jilin Oilfield in China.

A Gram-stain-negative, rod-shaped bacterial strain JS15-10A1T was isolated from oil production water. Its optimum growth was observed at 37 °C, pH 7.0, and 3% (w/v) NaCl. The 16S rRNA gene sequence of strain JS15-10A1T showed the highest similarities with Pseudomonas parafulva CB-1T (97.6%) and P. fulva IAM 1529T (97.5%). In addition, phylogenetic analyses based on multilocus sequence analyses with concatenating 16S rRNA, gyrB, rpoD, and rpoB genes indicated that strain JS15-10A1T was a member of genus Pseudomonas but discriminated from other species. Furthermore, whole-genome analyses revealed that average nucleotide identities and in silico DNA-DNA hybridization values of strain JS15-10A1T against its closest relatives were all below 76.7% and 21.1%, respectively. The major cellular fatty acids of strain JS15-10A1T were summed feature 8 (C18:1ω7c/C18:1ω6c), C16:0, C12:0, C17:0 cyclo, summed feature 3 (C16:1ω7c/C16:1ω6c), C12:0 3-OH, C10:0 3-OH, and C19:0 cyclo ω8c. The predominant quinone was ubiquinone Q-9. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unknown amino-lipid, and two unidentified lipids. The genome DNA G + C content was 60.0 mol%. On the basis of phylogenetic, phenotypic, physiological, and chemotaxonomic analyses, it can be concluded that strain JS15-10A1T represents a novel species in genus Pseudomonas, for which the name Pseudomonas jilinensis sp. nov. is proposed. The type strain is JS15-10A1T (= CGMCC 1.16072T = LMG 30036T).

Extracorporeal Shockwave Therapy for Chronic Knee Pain: A Multicenter, Randomized Controlled Trial.

CONTEXT: Osteoarthritis is the leading cause of chronic knee pain (CKP) in older adults. Medical practitioners often manage CKP using both pharmacological and nonpharmacological therapies. However, no studies have specifically focused on extracorporeal shockwave therapy (ESWT) for treatment of CKP. OBJECTIVE: The research team intended to explore the effectiveness and safety of ESWT for treatment of CKP. DESIGN: The study was a multicenter, randomized controlled trial. SETTING: The study took place at the Affiliated Hongqi Hospital of Mudanjiang Medical University (Mudanjiang, China) and at the People's Hospital of Yan'an (Yan'an, China). PARTICIPANTS: Participants were 72 patients with CKP at the 2 hospitals. INTERVENTION: Participants were randomly and equally divided into the intervention group, the ESWT group, and a control group. The intervention group received ESWT, whereas those in the control group received a placebo treatment. Participants in both groups were treated 3 times weekly for a total of 10 wk. OUTCOME MEASURES: The primary outcome was pain intensity measured using an 11-point numeric rating scale (NRS). The secondary outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and by tracking adverse events. All outcomes were evaluated at baseline and at the end of 5 wk and 10 wk of treatment (ie, postintervention). RESULTS: At both measured points, the ESWT exhibited greater benefits for patients with CKP, as measured by the scores for pain intensity on the NRS (P < .01) and the WOMAC subscale for pain (P < .01), compared with the placebo treatment. In addition, the ESWT group showed significantly less stiffness and greater improvements in function compared with the control group at the end of week 5 (P < .01) and of week 10 (P < .01). Furthermore, the study found no adverse events for either group. CONCLUSION: ESWT demonstrated an effective and safe profile for patients with CKP. Further studies with larger sample sizes are needed.

Rich Fat Hemangioma of the Parotid Gland in the Adult.

Hemangiomas are relatively rare tumors representing approximately 0.4% of all the salivary gland tumors and occur predominantly in the parotid. Most of the hemangiomas appear during the first year of life; however, are uncommon in adults. Moreover, the rich fat hemangiomas in the parotid are extremely rare. Magnetic resonance imaging is the most important radiologic methods for the diagnosis of the disease as its high resolution of soft tissue which helps to show the relationship with the adjacent structures.

On the Single-Crystal Structure of Tenofovir Alafenamide Mono-Fumarate: A Metastable Phase Featuring a Mixture of Co-Crystal and Salt.

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya® for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy® for the treatment of chronic hepatitis B. Vemlidy® is also a monotherapeutic regimen formulated as TAF hemifumarate (1; TAF:fumarate = 2:1). In this work, we report for the first time the single-crystal structure of TAF fumarate hemihydrate (2, TAF:fumarate:H2O = 2:2:1). Compound 2 is initially documented as a salt in which one proton of the fumaric acid migrates to the amine group of the adenine moiety in TAF. It was recently proposed that ca. 20-30% proton is transferred to the N atom on the aromatic adenine backbone. We herein provide definitive single-crystal X-ray diffraction results to confirm that 2, though phase pure, is formed as a mixture of co-crystal (75%) and salt (25%). It features two pairs of TAF fumarates, wherein one of the four H atoms on the fumaric acid is transferred to the N atom of the adjacent adenine moiety while the other three carboxylates remain in their intrinsic acid form. Compound 2 is a metastable phase during the preparation of 1 and can be isolated by halting the reaction during the refluxing of TAF and fumaric acid in acetonitrile (MeCN). Our report complements the previous characterizations of TAF monofumarate, and its elusive structural patterns are finally deciphered.

Miniaturization of the Whole Process of Protein Crystallographic Analysis by a Microfluidic Droplet Robot: From Nanoliter-Scale Purified Proteins to Diffraction-Quality Crystals.

To obtain diffraction-quality crystals is one of the largest barriers to analyze the protein structure using X-ray crystallography. Here we describe a microfluidic droplet robot that enables successful miniaturization of the whole process of crystallization experiments including large-scale initial crystallization screening, crystallization optimization, and crystal harvesting. The combination of the state-of-the-art droplet-based microfluidic technique with the microbatch crystallization mode dramatically reduces the volumes of droplet crystallization reactors to tens nanoliter range, allowing large-scale initial screening of 1536 crystallization conditions and multifactor crystallization condition optimization with extremely low protein consumption, and on-chip harvesting of diffraction-quality crystals directly from the droplet reactors. We applied the droplet robot in miniaturized crystallization experiments of seven soluble proteins and two membrane proteins, and on-chip crystal harvesting of six proteins. The X-ray diffraction data sets of these crystals were collected using synchrotron radiation for analyzing the structures with similar diffraction qualities as conventional crystallization methods.