Compound heterozygous missense mutations in a Chinese mucopolysaccharidosis type VI patient: a case report.

BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B (ARSB) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body. In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis. CASE PRESENTATION: A 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI. CONCLUSIONS: This paper reports a case of MPS VI confirmed by genetic diagnosis. MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

CT5, a subtle in vitro DNA assembling method based on the combination of FnCas12a and T5 exonuclease.

OBJECTIVE: To develop a new DNA assembly method based on FnCas12a and T5 exonuclease. RESULTS: We developed a method named as FnCas12a and T5 exonuclease (CT5) cloning system. FnCas12a performs site-directed cleavage to the target DNA fragments, and T5 exonuclease generates 20-30 nt single-stranded region at each end of the DNA fragments for homologous recombination-mediated DNA assembly. CT5 was applied to multi-fragment assembly and DNA cloning of large vectors (> 10 kb). The efficiencies were approximately 91.4% and 97%, respectively. In addition, CT5 cloning is also utilized for the "walking" of DNA elements, which enables subtle modification of the relative distances of DNA elements in plasmids. CONCLUSIONS: The CT5 method was a precise and exquisite DNA operating system and provided an ideal platform for the study of gene functions, genetic engineering and synthetic biology.

A single digestion, single-stranded oligonucleotide mediated PCR-independent site-directed mutagenesis method.

A PCR-independent in vitro site-directed mutagenesis method was established. Cas12a from Francisella novicida (FnCas12a) linearizes the plasmid with single digestion. T5 exonuclease removes the target nucleotide. A short single- or double-stranded mutagenic oligonucleotide introduces the mutation. This rapid and simple mutagenesis method is referred to as FnCas12a and T5 exonuclease mediated site-directed mutagenesis system (CT5-SDM). The platform is also suitable for the mutagenesis of plasmids larger than 10 kb. KEY POINTS: Site-directed mutagenesis mediated by single-stranded DNA. Removing target site with T5 exonuclease. Highly efficient cleavage of target DNA with FnCas12a.

Persistent secondary hyperparathyroidism caused by parathyromatosis and supernumerary parathyroid glands in a patient on haemodialysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common high-risk factor for mortality in end-stage renal disease, and parathyromatosis and supernumerary parathyroid glands are very rare causes of persistent SHPT. Preoperative diagnosis and removal of all hyperplastic parathyroid glands are challenging. We report a rare case of persistent SHPT due to parathyromatosis and supernumerary parathyroid glands and successful management by multiple imaging modalities. CASE PRESENTATION: A 53-year-old Chinese woman on haemodialysis experienced discomfort due to itching and bone pain due to persistent SHPT after parathyroidectomy. The supernumerary parathyroid glands and parathyromatosis were detected by multiple imaging modalities, including 99mTc-sestamibi (99mTc-MIBI) scans, ultrasonography and four-dimensional computed tomography (4D-CT) and then excised; pathological confirmation was performed. During follow-up, her serum calcium and parathyroid hormone levels were stable in the appropriate ranges, and no complications arose. CONCLUSIONS: Because of persistent SHPH after parathyroidectomy in patients with haemodialysis, multiple imaging modalities, including 99mTc-MIBI scans, 4D-CT and ultrasonography, are helpful for detecting supernumerary parathyroid glands and parathyromatoses. Accurate preoperative localization of this rare lesion is important for management, enabling the removal of all affected parathyroid tissues.

The prevalence of HIV among MSM in China: a large-scale systematic analysis.

BACKGROUND: The prevalence of HIV among men who have sex with men (MSM) has become a significant public health challenge. The aim was to comprehensively estimate the national prevalence of HIV among MSM and its time trends through a large-scale systematic analysis. METHODS: Systematic search of Cochrane Library, PubMed, EMBASE, CNKI, VIP, and Wanfang Data databases without language restriction for studies on the prevalence of HIV among MSM published before Dec.31, 2018. Studies were eligible for inclusion if they were published in the peer-reviewed literature and used validated assessment methods to assess the prevalence of HIV among MSM. Estimates were pooled using random-effects analysis. RESULTS: Data were extracted from 355 cross-sectional studies (571,328 individuals) covered 59 cities from 30 provinces and municipalities of China. The overall national prevalence of HIV among MSM from 2001 to 2018 was estimated to be 5.7% (95% CI: 5.4-6.1%), with high between-study heterogeneity (I2 = 98.0%, P <  0.001). Our study showed an increased tendency in the HIV prevalence as time progressed by meta-regression analysis (I2 = 95.9%, P <  0.0001). HIV prevalence was the highest in those aged 50 years and older with HIV prevalence of 19.3% (95%CI: 13.1-27.4%, N = 13). HIV was more prevalent in the illiterate population (16.8%), than in those who had received an education. Although the internet was a major venue for Chinese MSM seeking male sex partners (35.6, 95%CI: 32.3-39.9%, N = 101), seeking MSM in bathhouses/saunas had the highest associated prevalence of HIV (13.4, 95%CI: 10.3-17.1%, N = 22). The HIV prevalence among MSM varied by location: compared with other regions in China, HIV was highly prevalent among MSM in the southwest (10.7, 95%CI: 9.3-12.2%, N = 91). Compared to participants who sometimes or always used condoms, participants who had never used a condom in the past 6 months had a higher risk of HIV infection, with odds ratios of 0.1 (95%CI: 0.08-0.14). CONCLUSIONS: Our analysis provided reliable estimates of China's HIV burden among MSM, which appears to present an increasing national public health challenge. Effective government responses are needed to address this challenge and include the implementation of HIV prevention.

A rare lethal case of severe acute necrotizing pancreatitis due to a parathyroid adenoma in a third-trimester pregnant woman.

BACKGROUND: Primary hyperparathyroidism (PHPT), which is mostly caused by a parathyroid adenoma, is fairly common in postmenopausal women but is relatively rare in pregnant women. PHPT-induced pancreatitis during pregnancy is associated with significant maternal and foetal morbidity and mortality. Diagnosis is challenging because of non-specific symptoms and changes in maternal calcium homeostasis. Information about the optimal treatment strategy for the prevention of catastrophic consequences to the mother and foetus is limited. Here, we describe a rare lethal case of severe acute necrotizing pancreatitis due to a parathyroid adenoma in a woman in her third trimester of pregnancy. CASE PRESENTATION: A previously healthy 24-year-old Chinese woman at 37 weeks of gestation presented with persisting epigastric pain, nausea and bilious vomiting for 1 day. PHPT-induced acute necrotizing pancreatitis was diagnosed on the basis of her serum calcium, parathyroid levels and imaging results. A caesarean section and parathyroidectomy were performed at 1 day and 11 days after admission, respectively. Histological examination confirmed a right inferior parathyroid adenoma with a size of 2.0 × 1.5 cm. Following the parathyroidectomy, the patient had eucalcaemia and presented normal parathyroid hormone (PTH) levels. Although the foetus was normal, the patient died of multiple organ failure due to severe pancreatitis. CONCLUSIONS: PHPT-induced acute necrotizing pancreatitis is a rare clinical entity and life-threatening condition to both the mother and the foetus during pregnancy. Early diagnosis can be challenging and is crucial. Appropriate treatment according to the patient's condition may effectively reduce maternal and foetal mortality.

Evaluation of Iodine-125 Interstitial Brachytherapy Using Micro-Positron Emission Tomography/Computed Tomography with 18F-Fluorodeoxyglucose in Hepatocellular Carcinoma HepG2 Xenografts.

BACKGROUND Iodine-125 interstitial brachytherapy (125I-IBT) is a promising treatment option for unresectable hepatocellular carcinoma (HCC). This study evaluated the usefulness of micro-positron emission tomography/computed tomography (micro-PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) in assessing response to 125I-IBT in HCC HepG2 xenograft. MATERIAL AND METHODS Twelve mice with bilateral HepG2 xenografts were divided into 3 equal groups implanted with iodine-125 seeds into the left xenografts with a dose of 30, 50, and 80 Gy, respectively, and the right xenografts were used as internal controls. Before and 28 days after treatment, the 18F-FDG micro-PET/CT was performed. The ratios of left to right xenografts of tumor volume (RTV), maximum standardized uptake value (RSUVmax), mean optical density of caspase-3 expression (RMODcaspase-3), and apoptosis index (RAI) were compared. RESULTS The RTV means of the 50 and 80 Gy groups were significantly lower than in the 30 Gy group after treatment (P<0.01) and the RTV means after treatment were lower than baseline in the 50 and 80 Gy groups (P<0.05). The RSUVmax mean after treatment was lower than baseline in the 80 Gy group (P<0.05). The RMODCaspase-3 and RAI means of the 80 Gy group were higher than in the 30 Gy group (P<0.05). The RSUVmax was correlated negatively to RMODcaspase-3 (r=-0.624, P<0.05) and RAI (r=-0.651, P<0.05). CONCLUSIONS This study suggest that 125I-IBT inhibits tumor growth via upregulating caspase-3 expression and prompting apoptosis in HCC HepG2 xenografts. The 18F-FDG micro-PET/CT may be a useful functional imaging modality to assess early response to 125I-IBT in HCC HepG2 xenograft.

Simultaneous intrathyroidal parathyroid adenomas and multifocal papillary thyroid carcinoma in a patient with kidney transplantation: a case report.

BACKGROUND: Persistent hyperparathyroidism after kidney transplantation has been associated with adverse outcomes. Parathyroidectomy is the definitive treatment approach, but the success of parathyroidectomy relies on the accurate preoperative localization of the culprit parathyroid lesions. Simultaneous intrathyroidal parathyroid adenomas and multifocal papillary thyroid carcinoma present important diagnostic challenges. Here, we describe a patient with kidney transplantation who underwent successful surgery after being evaluated with functional and structural imaging. CASE PRESENTATION: A 53-year-old man presented with potentially malignant multifocal thyroid nodules by ultrasonography 2 years after kidney transplantation. The patient had hypercalcaemia and persistent hyperparathyroidism. Thyroid papillary carcinoma was confirmed in the left thyroid nodules by fine-needle aspiration biopsy. The right superior thyroid hypoechoic nodule was 1.2 cm in size and showed marked uptake of the tracer 99mTcO4-sestamibi during single-photon emission computed tomography/computed tomography (SPECT/CT); additionally, a cystic parathyroid lesion without tracer uptake was present behind the left superior pole of the thyroid. The histological examination demonstrated the coexistence of right intrathyroidal parathyroid adenomas, left cystic parathyroid nodular hyperplasia and multifocal papillary thyroid carcinoma. At the 6-month follow-up, the serum calcium levels were within the normal range, and the patient's kidney function remained stable. CONCLUSIONS: Simultaneous intrathyroidal parathyroid adenomas and multifocal papillary thyroid carcinoma in a patient with kidney transplantation is a rare clinical scenario. Physicians must be aware that the combination of functional (SPECT/CT) and structural (ultrasonography) imaging is highly successful in diagnosing patients with coexistent intrathyroidal parathyroid adenomas and papillary thyroid carcinoma.

Prevalence of dementia in the People's Republic of China from 1985 to 2015: a systematic review and meta-regression analysis.

BACKGROUND: In China, the most populous developing country in the world, dementia represents a serious challenge. We performed a large-scale systematic review and meta-regression analysis to elucidate the prevalence of dementia and its subtypes and to identify potential factors underlying the differences between articles. METHODS: A comprehensive literature search was conducted in the following databases to identify studies published up to December 2015: Cochrane Library, CBMDISK, Chongqing VIP, CNKI, PubMed and EMBASE. All statistical analyses (including subtype and meta-regression analyses) were performed with R version 3.3.3. RESULTS: In total, 51 surveys were selected. The pooled prevalence rates of dementia and its main subtypes, namely, Alzheimer's disease (AD) and vascular dementia (VAD), for the population aged 55 years and older were 4.03, 2.44 and 1.09%, respectively. The outcomes showed that the meta-regression analysis was affected by the publication year, sample size, region and diagnostic criteria. CONCLUSIONS: Our analysis provided reliable estimates of the prevalence of dementia/ AD/ VD over the past 30 years, which may be affected by education level, and diagnostic criteria. The prevalence of AD/VAD was higher in northern than in southern China, which warrants further study.

Synthesis of novel 10-hydroxycamptothecin derivatives utilizing topotecan hydrochloride as ortho-quinonemethide precursor.

A series of 9-(alkylthiomethyl)-10-hydroxycamptothecins and pyrano-fused camptothecin derivatives were synthesized via the reaction of topotecan hydrochloride with various thiols and alkyl vinyl ethers respectively. In the reactions, topotecan hydrochloride was utilized as ortho-quinonemethide (o-QM) precursor. The configuration of 19 was determined by (1)H NMR and NOESY spectra as syn-isomers, suggesting that the cycloaddition of topotecan with alkyl vinyl ethers could undergo a hetero Diels-Alder reaction. All the synthesized compounds were screened on cancer cell lines HepG2, KB, HCT-8 and SGC7901. Some compounds were selected to assess their inhibitory activity against Topo I via Topo I mediated DNA cleavage assays. The results showed that among those tested 9-(alkylthiomethyl)-10-hydroxycamptothecins, the compounds with bulkier hydrophobic side chains at 9-position have better bioactivities. As well as all pyrano-fused camptothecins possess antiproliferative activity against the tested cancer cell lines. Docking studies suggested that there are more interactions between the novel analogues and the binding site of Topo I.

Evaluation of the factors affecting the maximum standardized uptake value of metastatic lymph nodes in different histological types of non-small cell lung cancer on PET-CT.

BACKGROUND: To evaluate the factors affecting the maximum standardized uptake value (SUVmax) of metastatic lymph nodes in different histological types of non-small cell lung cancer (NSCLC) on integrated positron emission tomography and computed tomography (PET-CT). METHODS: This was a retrospective, single-institution review of 122 patients with pathologically proven NSCLC who had PET-CT scanning at the same center. Lymph node metastases were pathologically confirmed in tissue specimens from surgical patients. Statistical evaluation of PET-CT results was performed on a per-nodal-station basis. RESULTS: The tumor SUVmax of squamous cell carcinoma (SCC) (11.0 ± 4.1) was higher than that of adenocarcinoma (AC) (7.4 ± 4.4) (P < 0.01), however, the SUVmax of the metastatic lymph nodes did not differ between the SCC (4.6 ± 3.1) and AC groups(3.6 ± 2.5) (P = 0.221). The SUVmax of metastatic lymph nodes was positively correlated with lymph node size but not with the primary tumor SUVmax, primary tumor size, tumor location and tumor differentiation. The frequency of a SUVmax of lymph nodes ≥2.5 was 44%, 80%,100% in SCC group and 39%, 59%, 90% in AC group when the short-axis diameter of metastatic lymph node was <10 mm, 10-15 mm, and > 15 mm, respectively. The low sensitivity for metastatic lymph nodes on PET-CT was increased when the SUVmax cut-off for malignancy was considered to be above the normal background compared with that when the SUVmax cut-off was above 2.5. CONCLUSIONS: There was no difference in the SUVmax of metastatic lymph nodes in the SCC and AC groups. The SUVmax of metastatic lymph nodes was positively correlated with metastatic lymph node size. There was a high false negative rate if lymph nodes with a short-axis diameter less than 10 mm and a extremely low false negative rate if lymph nodes with a short-axis diameter higher than 15 mm. Although an increased sensitivity may be achieved by decreasing the SUVmax cut-off, invasive staging may still be required for negative lymph nodes due to the lower sensitivity of PET-CT in both SCC and AC.

Case report: [18F]FAPI-42 PET/CT visualize primary adenoid cystic carcinoma not detected by [18F]FDG.

Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. Still, its growth and invasion progress is slow, and its hematogenous metastasis is ACC's most common distant metastasis. Because of the broad expression and low background uptake of fibroblast activation protein (FAP) in tumor stroma, FAPI is considered another potential tracer of ACC in addition to FDG. In this case, we report a patient who was diagnosed with metastatic ACC liver cancer by fine needle aspiration biopsy (FNAB) and underwent PET/CT examination of [18F]FDG and [18F]FAPI-42 to find the primary cancer lesion. Finally, the primary cancer lesion was found in the left submandibular gland and was pathologically confirmed as ACC after resection.

Three-Dimensional Cross-Linking Network Coating for the Flame Retardant of Bio-Based Polyamide 56 Fabric by Weak Bonds.

Weak bonds usually make macromolecules stronger; therefore, they are often used to enhance the mechanical strength of polymers. Not enough studies have been reported on the use of weak bonds in flame retardants. A water-soluble polyelectrolyte complex composed of polyethyleneimine (PEI), sodium tripolyphosphate (STPP) and melamine (MEL) was designed and utilized to treat bio-based polyamide 56 (PA56) by a simple three-step process. It was found that weak bonds cross-linked the three compounds to a 3D network structure with MEL on the surface of the coating under mild conditions. The thermal stability and flame retardancy of PA56 fabrics were improved by the controlled coating without losing their mechanical properties. After washing 50 times, PA56 still kept good flame retardancy. The cross-linking network structure of the flame retardant enhanced both the thermal stability and durability of the fabric. STPP acted as a catalyst for the breakage of the PA56 molecular chain, PEI facilitated the char formation and MEL released non-combustible gases. The synergistic effect of all compounds was exploited by using weak bonds. This simple method of developing structures with 3D cross-linking using weak bonds provides a new strategy for the preparation of low-cost and environmentally friendly flame retardants.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Effects of drought and salt stress on seed germination and seedling growth of Elymus nutans.

Drought and soil salinization are global environmental issues, and Elymus nutans play an important role in vegetation restoration in arid and saline environments due to their excellent stress resistance. In the process of vegetation restoration, the stage from germination to seedling growth of forage is crucial. This experiment studied the effects of PEG-6000 simulated drought stress and NaCl simulated salinization stress on the germination of E. nutans seeds, and explored the growth of forage seedlings from sowing to 28 days under drought and salinization stress conditions. The results showed that under the same environmental water potential, there were significant differences in responses of seed germination, seedling growth, organic carbon, total nitrogen and total phosphorus of above-ground and underground parts of E. nutans to drought stress and salinization stress. Using the membership function method to comprehensively evaluate the seed germination and seedling indicators of E. nutans, it was found that under the same environmental water potential, E. nutans was more severely affected by drought stress during both the seed germination and seedling growth stages. E. nutans showed better salt tolerance than drought resistance.

Development of 99mTc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer.

BACKGROUND: N-cadherin is considered a characteristic protein of EMT and has been found to be closely related to tumor resistance. In this study, a novel molecular imaging probe, 99mTc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated. METHODS: ADH-1 was labeled indirectly with 99mTc. Radiochemical purity and stability, partition coefficients and pharmacokinetics were evaluated. Additionally, the fluorescent probe of ADH-1 was synthesized to study tumor uptake in cells level and in vivo. Biodistribution analysis and small animal SPECT/CT were performed in PC9GR and PC9 tumor-bearing mice. RESULTS: 99mTc-HYNIC-ADH-1 was highly stable (radiochemical purity ≥ 98% in PBS and serum after 24 h). A cell binding study and fluorescence imaging showed that the uptake was significantly higher in PC9GR cells (gefitinib-resistant) than in PC9 cells (nonresistant) (p < 0.05). Biodistribution analysis showed rapid blood clearance and significant uptake in the kidney and resistant tumor. Small animal SPECT/CT studies showed that uptake in PC9GR tumors (T/NT = 7.73 ± 0.54) was significantly higher than that in PC9 tumors (T/NT = 3.66 ± 0.78) at 1 h (p = 0.002). CONCLUSIONS: The 99mTc-HYNIC-ADH-1 molecular probe has a short synthesis time, high labeling rate, high radiochemical purity and good stability, does not require purification, is characterized by rapid blood clearance and is mainly excreted through the urinary system. 99mTc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC.

The value of PET/CT for the diagnosis and evaluation of immunotherapy in occult primary renal cell carcinoma: a case report.

Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.

Influence of relative positions of the heat carrier and lateral canal opening on gutta-percha obturation of lateral canals in a three-dimensional-printed model.

Background/purpose: Effective filling of the lateral canals is of great significance in successful root canal treatment, but it is generally being challenging. This study aimed to evaluate the influence of relative positions of the heat carrier and lateral canal opening on gutta-percha obturation of lateral canals in a three-dimensional (3D)-printed model. Materials and methods: Thermal conductivity and real-time temperature transmission of gutta-percha were investigated using laser flash and thermal infrared analyses. 3D-printed root canal models with lateral canals at 1, 3, and 5 mm from the apex were fabricated, and different relative positions of the heat carrier were tested. The obturation process was recorded on video, and the obturation depth of the lateral canals was observed using X-ray micro-computed tomography. Results: Gutta-percha showed low thermal conductivity of 1.07 W/(m·K), and heating increased the temperature of gutta-percha above 60 °C only within 1 mm beyond the heat carrier tip. For lateral canals at 1 and 3 mm from the apex, gutta-percha penetrated further with deeper penetration of the heat carrier (P < 0.05). For 5-mm lateral canals, the heat carrier was always at apical level and the gutta-percha obturation depth was more at 2 mm apically than at 3 or 4 mm (P < 0.05). Conclusion: Gutta-percha is a poor thermal conductor. The position of the heat carrier in relation to the lateral canal opening affects obturation depth. Only when the heat carrier reaches or passes the lateral canal opening can gutta-percha penetrate a lateral canal.

Preliminary Study on Human Adipose Stem Cells Promoting Skin Wound Healing through Notch Signaling Pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) have been documented as possible candidates for wound healing treatment because their use could reinforce the regenerative capacity of many tissues. Human adipose stem cells (hADSCs) have the advantages of easy access, large quantity and easy operation. They can be fully applied in the treatment of skin wounds. OBJECTIVE: In this study, we aim to explore the roles and potential mechanisms of hADSCs in cutaneous wound healing. METHODS: hADSCs were obtained from human subcutaneous fat. Adipocytes and osteocytes differentiated from hADSCs were determined by staining with Oil Red O and alkaline phosphatase (ALP), respectively. We assessed the effects of hADSCs and hADSC conditional medium (CM) on wound healing in an injury model of mice. Then, we investigated the biological effects of hADSCs on human keratinocytes HaCAT cells in vitro. RESULTS: The results showed that hADSCs could be successfully differentiated into osteogenic and lipogenic cells. hADSCs and hADSCs-CM significantly promote skin wound healing in vivo. hADSCs significantly promoted HaCAT cell proliferation and migration by activating the Notch signaling pathway and activated the AKT signaling pathway by Rps6kb1 kinase in HaCAT cells. In addition, we found that hADSCs-mediated activation of Rps6kb1/AKT signaling was dependent on the Notch signaling pathway. CONCLUSION: We demonstrated that hADSCs can promote skin cell-HaCAT cell proliferation and migration via the Notch pathway, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of skin injury.

[18F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors.

Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers. Methods: In this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo. Results: Radiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor. Conclusion: [18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.