[A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children].

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95%CI 0.593-0.771, P<0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

[Analysis of complications and learning curve effects related to deep brain stimulation surgery in 822 Parkinson's disesase patients with the same surgeon].

Objective: To analyze the complications related to deep brain stimulation(DBS) surgery in Parkinson's disease(PD) patients and to determine whether there is a learning curve effect in terms of complications. Methods: Retrospective analysis of the DBS surgical data of 822 PD patients performed by the same surgeon at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) from December 2012 to December 2022. The complications related to DBS were evaluated and analyzed the complications of every 100 DBS surgery were further analyzed. Results: A total of 822 PD patients, 453 males and 369 females, aged 31-80 years old, were included. The minimum follow-up period after DBS surgery is 6 months. Surgical related complications occurred in 55 patients (6.69%), including 5 patients (0.61%) with slight bleeding around the electrode, 1 patient (0.12%) with cerebral infarction, 4 patients (0.49%) with postoperative epilepsy, 42 patients (5.11%) with postoperative delirium, 2 patients (0.24%) with respiratory distress, and 1 patient (0.12%) with acute cardiac insufficiency. There were 16 cases (1.94%) of hardware related complications in DBS, of which 4 cases (0.48%) had infection, 1 case (0.12%) had a broken angle at the connection between the pulse generator and the extension wire, 8 cases (0.97%) had an excessively tight extension wire, and 3 cases (0.36%) had an IPG bag hematoma. In the infected cases, 2 patients removed IPG and extension wires. There were 7 cases (0.85%) of stimulus related complications, including 4 cases (0.61%) with programmed sensory abnormalities, 1 case (0.12%) with postoperative abnormal movements and dance like movements, and 2 cases (0.24%) with psychiatric symptoms. A comprehensive analysis was conducted on the above complications, among which 8 cases (0.97%) were relatively serious complications. After active treatment, satisfactory results were achieved, and none of them affected the patient's DBS treatment effect and no patients died. For every 100 cases of DBS surgery complications were analyzed, the percentage of complications decreased significantly from 14.50% (58 cases) in the first 400 cases to 4.73% (20 cases) in the last 400 cases (P<0.001). Conclusion: DBS surgery is safe and has an acceptable low incidence of complications. The incidence of complications also decreases with the accumulation of experience, showing a learning curve effect.

[Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm].

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN). METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, ß-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, ß-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN. RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. ß-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. ß-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05). CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

[The identification process of the state of fractures by orthopedic surgeons before radiography].

Fracture treatment requires a detailed understanding of the state and displacement of the fracture site. Before X-ray was discovered by Wilhelm Conrad Röntgen in 1895, it was almost impossible to know the location of the fracture fragments wrapped in skin and muscle. The early classical theories for this were mainly based on the medical theories of Hippocrates and Galen. The more clinical cases were accumulated, the more cases were inconsistent with the classical theories. Doctors either chose to stick to the classics for their diagnose or believed in their own judgment. The development of anatomy gradually became a means of examining fracture fragments. With the development of anatomy during and after the "Renaissance", doctors began to collect a large number of bone specimens and communicated this information to other doctors. Doctors discarded the strict adherence to early classical theories, and finally constructed a theoretical model to explain clinical questions with anatomical evidence.

Gender and sex considerations in HIV and bone health.

PURPOSE OF REVIEW: People with HIV (PWHIV) are at increased risk for osteoporosis and fractures, because of the effects of HIV and inflammation and antiretroviral therapy (ART) initiation as well as traditional risk factors. This review from recent literature focuses on sex differences in rates of bone disease, risk of fractures, and effects of ART. RECENT FINDINGS: Women with HIV in resource-constrained settings experience bone loss because of the additive effect of initiating TDF-containing ART during pregnancy, lactation, and menopause. Children and adolescents experience lower bone accrual during the pubertal growth years. There has been less focus on bone health in recent trials of ART containing tenofovir alafenamide and/or integrase inhibitors. Very few clinical trials or studies compare sex-specific changes in inflammation, immune activation, response to ART and bone turnover or change in BMD resulting in significant knowledge gaps. SUMMARY: More data is needed to determine changes in prevalence of osteopenia, osteoporosis, and fractures in the era of immediate initiation of ART at high CD4 cell counts and the use of more bone-friendly ART. The long-term effects of ART and low bone mass on fractures in the ageing population of PWHIV is yet to be realized.

[Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodies in vitro].

OBJECTIVE: To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms. METHODS: EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, ß-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment. RESULTS: The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of ß-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, ß-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05). CONCLUSION: Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/ß-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.

DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS.

To evaluate the potential anticancer effects of 1175 FDA-approved drugs, cell viability screening was performed using 25 human cancer cell lines covering 14 human cancer types. Here, we focus on the action of paroxetine, which demonstrated greater toxicity toward human gastric adenocarcinoma cell-line AGS cells compared with the other FDA-approved drugs, exhibiting an IC50 value lower than 10 µM. Evaluation of the underlying novel mechanisms revealed that paroxetine can enhance DNA damage in gastric cancer cells and involves downregulation of Rad51, HR23B and ERCC1 expression and function, as well as nucleotide shortage. Enhancement of autophagy counteracted paroxetine-induced apoptosis but did not affect paroxetine-induced DNA damage. Paroxetine also enhanced ROS generation in AGS cells, but a ROS scavenger did not improve paroxetine-mediated DNA damage, apoptosis, or autophagy, suggesting ROS might play a minor role in paroxetine-induced cell toxicity. In contrast, paroxetine did not enhance DNA damage, apoptosis, or autophagy in another insensitive gastric adenocarcinoma cell-line MKN-45 cells. Interestingly, co-administration of paroxetine with conventional anticancer agents sensitized MKN-45 cells to these agents: co-treated cells showed increased apoptosis relative to MKN-45 cells treated with the anticancer agent alone. Unequivocally, these data suggest that for the first time that paroxetine triggers cytotoxicity and DNA damage in AGS cells at least partly by reducing the gene expression of Rad51, HR23B, and ERCC1. Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.

[Clinical significance of No.11p posterior lymph nodes dissection in gastric cancer surgery].

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

[Emulation pulmonary nodules localization model:a novel non-invasive localization technique in resection of pulmonary nodules].

Objective: To explore the accuracy and efficiency of a novel 3D-printed emulation localization model of small pulmonary nodules in lung surgery. Methods: From April 2020 to April 2021, a total of 66 patients were selected in the study, who underwent localization and resection of pulmonary nodules with video-assisted thoracoscopic surgery (VATS) guided by the 3D-printed emulation localization model at Department of Thoracic Surgery, West China Hospital of Sichuan University. There were 13 males and 53 females, aged from 25 to 79 (52.7±11.4) years. Of all patients, 24 (36.4%) had single pulmonary nodule, and 42 (63.6%) had synchronous multiple pulmonary nodules. The chest high-resolution CT image data were utilized for digital reconstruction and 3D printing to make a tailored life-size emulation pulmonary nodules localization model, which was used to navigate real-time intraoperative localization of nodules. Clinical data including operative parameters, localization information, resection types and pathological findings of nodules were analyzed. The pulmonary nodules that doctors planned to resect were categorized into two categories:major nodules and additional nodules, according to their presence of invasion and radiological risk factors. The accuracy of localization and resection efficiency of nodules were evaluated in accordance with the categories of the nodules respectively. Results: On the basis of preoperative evaluation, there were 71 major nodules with median maximal diameter of 0.9 (0.6-1.3) cm, and 77 additional nodules with median maximal diameter of 0.5 (0.4-0.7) cm. All patients underwent VATS surgery, 52 of them (78.8%) were treated with uniportal VATS and 14 (21.2%) with triportal VATS. Among the patients with single nodule, 18 segmentectomies and 6 wedge resections were performed; whereas among the patients with multiple nodules, 5 segmentectomies, 14 wedge resections, and 23 combined pulmonary resections (including 2 cases of lobectomy+segmentectomy, 7 cases of lobectomy+wedge resections, and 14 cases of segmentectomy+wedge resections) were achieved. The median operative time was 93 (45-240) min, and the median resection time for all nodules was 51.4 (6.7-147.0) min. All major nodules were successfully resected and visibly dissected after removal, and all additional nodules were successfully resected with 85.7%(66/77) nodules visibly dissected. The accuracy rate of localization of both types of nodules was 100%. All major nodules were malignant, and the malignancy rate of additional nodules was 21.2%(14/66). Conclusion: This novel 3D-printed emulation localization model of small pulmonary nodules proved to be a non-invasive, accurate and efficient technique. Not only that, it has a unique advantage in localization of synchronous multiple pulmonary nodules.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.

Ultrasound-Guided Pudendal Nerve Block Combined with Propofol Deep Sedation versus Spinal Anesthesia for Hemorrhoidectomy: A Prospective Randomized Study.

Background and Objectives. Several anesthesia techniques were applied to hemorrhoidectomy, but postoperative pain and urinary retention were still two unsolved problems. The aim of this prospective randomized study was to evaluate the effect of ultrasound-guided pudendal nerve block (PNB) combined with deep sedation compared to spinal anesthesia for hemorrhoidectomy. Methods. One hundred and twenty patients undergoing Milligan-Morgan hemorrhoidectomy were randomized to receive PNB combined with deep sedation using propofol (Group PNB, n = 60) or spinal anesthesia (Group SA, n = 60). Pain intensity was assessed using the visual analogue scale (0: no pain to 10: worst possible pain). The primary outcome was pain scores recorded at rest at 3, 6, 12, 24, 36, and 48 h and on walking at 12, 24, 36, and 48 h postoperatively. Secondary outcomes were analgesic consumption, side effects, and patient satisfaction after surgery. Results. Ultrasound-guided bilateral PNB combined with deep sedation using propofol could successfully be applied to Milligan-Morgan hemorrhoidectomy. Postoperative pain intensity was significantly lower in Group PNB compared to Group SA at rest at 3, 6, 12, 24, 36, and 48 h (p < 0.001) and during mobilization at 12, 24, 36, and 48 h (p < 0.001) postoperatively. Sufentanil consumption in Group PNB was significantly lower than that in Group SA, during 0-24 h (p < 0.001) and during 24-48 h (p < 0.001) postoperatively. Urinary retention was significantly lower in Group PNB compared to Group SA (6.9% vs 20%, p=0.034). The patients in Group PNB had higher satisfaction compared to Group SA (p < 0.001). Conclusions. Ultrasound-guided PNB combined with propofol sedation is an effective anesthesia technique for Milligan-Morgan hemorrhoidectomy.

Zinc oxide nanoparticles promotes liver cancer cell apoptosis through inducing autophagy and promoting p53.

OBJECTIVE: Emerging evidence has highlighted the promising potential of the application of Zinc Oxide nanoparticles (nano-ZnO) but the mechanism by how it functions in liver cancer remains elusive. We aimed to explore the effect of nano-ZnO on liver cancer cells. MATERIALS AND METHODS: Liver cancer cells Huh7 cells were transfected with GFP-LC3, and then, treated with DMSO, Sorafenib, and nano-ZnO respectively to set blank group, Sorafenib control group, and nano-ZnO group followed by the analysis of the expression of GFP-LC3, p53, and Caspase by Western blot and RT-qPCR, cell apoptosis and viability by flow cytometry and CCK-8 assay. RESULTS: With a diameter of nano-ZnO 14.13±0.92 nm, the amount of GFP-LC3 protein was increased after treatment of nano-ZnO. Besides, the expressions of GFP-LC3, p53, and Caspase in Sorafenib group and nano-ZnO group were significantly higher than that of control group, while their levels were highest in nano-ZnO group (p<0.05). In nano-ZnO group, the values of D450nm at 24 h, 48h, and 72 h were 0.56±0.06, 0.39±0.05, and 0.22±0.04, respectively, and the apoptotic rate (83.11±2.79%) was significantly lower than that of blank group and control group. CONCLUSIONS: Nano-ZnO induced autophagy, upregulated the p53 gene, and facilitated the apoptosis of liver cancer cells, indicating that nano-ZnO might be a therapeutic approach for the treatment of liver cancer patients.

LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis.

Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-ß-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-ß-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

[Epidemic situation of malaria in Lishui City from 2013 to 2018].

OBJECTIVE: To analyze the epidemic situation and epidemiological characteristics of malaria in Lishui City from 2013 to 2018, so as to provide the evidence for formulating the malaria control strategy. METHODS: The data pertaining malaria cases in Lishui City from 2013 to 2018 were captured from National Notifiable Communicable Disease Reporting System and the Information System for Parasitic Diseases Control and Prevention, and the epidemiological features of malaria cases were analyzed. RESULTS: A total of 119 malaria cases were reported in Lishui City from 2013 to 2018, including 101 cases with falciparum malaria (84.87%), 6 cases with vivax malaria (5.04%), 8 cases with ovale malaria (6.72%), and 4 cases with mixed infection (3.36%). Among the 119 cases, there were one local case with blood transfusion-induced malaria and 118 cases with over- seas imported malaria. There were 98.32% of the imported malaria cases acquiring infection in African countries, and most cases were reported in Qingtian County (60.50%) and Liandu District (22.69%). In addition, 86.55% of the malaria cases were detected in individuals at ages of 20 to 50 years, and most cases were found in oversea workers (52.94%) and businessmen (38.65%). CONCLUSIONS: Most of the malaria cases in Lishui City are imported from Africa, and the monitoring and health education pertaining to malaria control knowledge requires to be intensified among high-risk populations.

MiR-199a modulates autophagy and inflammation in rats with cerebral infarction via regulating mTOR expression.

OBJECTIVE: The aim of this study was to investigate the roles of micro ribonucleic acid (miR)-199a in rats with cerebral infarction by regulating mammalian target of rapamycin (mTOR). MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly assigned into three groups, including: sham group (n=12), model group (n=12) and miR-199a mimics group (n=12). In sham group internal and external carotid arteries were exposed. The ischemia-reperfusion model was successfully established using suture embolization in the other two groups. After modeling, rats in sham group and model group were intraperitoneally injected with normal saline. However, rats in miR-199a mimics group were injected with miR-199a mimics. Following intervention for 3 d, sampling was conducted. Neurological deficit was evaluated in rats based on the Zea-Longa scoring system. Hematoxylin-eosin (HE) staining was performed to observe neuronal morphology. The expression of mTOR was detected using immunohistochemistry, and the relative expression level of tau protein was determined via Western blotting (WB). Besides, the messenger RNA (mRNA) expressions of mTOR and tau were detected by quantitative Polymerase Chain Reaction (qPCR). Finally, inflammatory factor content was measured through enzyme-linked immunosorbent assay (ELISA). RESULTS: Model group and miR-199a mimics group exhibited a substantially higher Zea-Longa score than sham group (p<0.05). Compared with model group, the Zea-Longa score rose prominently in miR-199a mimics group (p<0.05). According to the results of HE staining, the structure of neurons in sham group was clear and intact, while the structure of neurons in model group was disordered. Meanwhile, neuronal morphology in miR-199a mimics group was significantly worse than that in model group (p<0.05). Immunohistochemistry results demonstrated that the positive expression level of mTOR was considerably upregulated in both model group and miR-199a mimics group in comparison with sham group (p<0.05). Moreover, its positive expression level in miR-199a mimics group was markedly higher that in model group (p<0.05). Based on the results of WB, model and miR-199a mimics groups exhibited a remarkably higher relative expression level of tau protein than sham group (p<0.05). However, the relative expression level of tau protein in miR-199a mimics group was prominently higher than that in model group (p<0.05). QPCR results manifested that the relative mRNA expression levels of mTOR and tau in model group and miR-199a mimics group were dramatically higher than those in sham group (p<0.05). Compared with those in model group, the relative mRNA expression levels of mTOR and tau increased significantly in miR-199a mimics group (p<0.05). ELISA results revealed that model group and miR-199a mimics group had prominently higher content of inflammatory factors than sham group (p<0.05). In addition, content of inflammatory factors in miR-199a mimics group was considerably higher than that in model group (p<0.05). CONCLUSIONS: MiR-199a modulates mTOR expression to exert important regulatory effects on the autophagy and inflammation in rats with cerebral infarction.

Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity.

OBJECTIVE: This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing. METHODS: Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP+ FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface. RESULTS: hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFP+ FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients. CONCLUSION: We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders.

An energy efficient time-mode digit classification neural network implementation.

This paper presents the design of an ultra-low energy neural network that uses time-mode signal processing). Handwritten digit classification using a single-layer artificial neural network (ANN) with a Softmin-based activation function is described as an implementation example. To realize time-mode operation, the presented design makes use of monostable multivibrator-based multiplying analogue-to-time converters, fixed-width pulse generators and basic digital gates. The time-mode digit classification ANN was designed in a standard CMOS 0.18 µm IC process and operates from a supply voltage of 0.6 V. The system operates on the MNIST database of handwritten digits with quantized neuron weights and has a classification accuracy of 88%, which is typical for single-layer ANNs, while dissipating 65.74 pJ per classification with a speed of 2.37 k classifications per second. This article is part of the theme issue 'Harmonizing energy-autonomous computing and intelligence'.

[Protective effect of excretory-secretory protein from adult Trichinella spiralis on ovalbumin-induced allergic rhinitis in mice].

OBJECTIVE: To investigate the protective effect of excretory-secretory protein (AES) from adult Trichinella spiralis on ovalbumin (OVA)-induced allergic rhinitis in mice. METHODS: Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 µg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-ß were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope. RESULTS: There was a significant difference in the mouse behavioral scores among the three groups (F = 110.12, P < 0.01). The mouse behavioral score was significantly higher in Group B than in Group A (7.17 ± 0.75 vs. 1.33 ± 0.52, P < 0.01), and more remarkable pathological damages of mouse nasal mucosa were seen in Group B than in Group A, while the mouse behavioral score was significantly decreased in Group C than in Group B (P < 0.01), and the pathological damages of mouse nasal mucosa remarkably alleviated in Group C relative to Group B. There was a significant difference in serum IFN-γ level among the three groups (F = 7.50, P < 0.01) and the serum IFN-γ level in Group B was significantly lower than in group A and C (both P < 0.05). There were significant differences in serum IL-4 (F = 470.81, P < 0.01) and IL-5 levels (F =68.20, P < 0.01) among the three groups, and significantly greater serum IL-4 and IL-5 levels were detected in Group B than in Group A (P < 0.01), while significantly lower serum IL-4 and IL-5 levels were detected in Group C than in Group B (P < 0.01). There were significant differences in serum IL-10 (F = 174.91, P < 0.01) and TGF-ß levels (F = 9.39, P < 0.01) among the three groups, and significantly greater serum IL-10 and TGF-ß levels were seen in Group C than in Group B (both P < 0.05). CONCLUSIONS: T. spiralis AES has a remarkable protective activity against OVA-induced allergic rhinitis in mice.

[Clinical effects of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face].

Objective: To explore the clinical effects and key techniques of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face. Methods: From January 2008 to November 2018, 22 patients with extensive burn scars in the face were admitted to the Department of Plastic Surgery of Dongguan Kanghua Hospital and the Department of Plastic Surgery of Dermatology Hospital of Southern Medical University, with 3 males and 19 females, aged from 4 to 48 years. There were 16 cases of type Ⅱ and 6 cases of type Ⅲ in facial scars. Before the first stage of expansion surgery, Doppler blood flow survey meter or multi-slice CT was used to locate the perforator vessels. One to four expanders with rated capacity ranged from 100 to 600 mL were placed in the patients. We gave 20% to 30% of the rated capacity of expander intro-operation and common injection with 10% to 15% of the rated capacity of expander per week post-operation until the volume reached 1.5 to 2.5 times of the rated capacity of expander during the past 3 to 4 months. At the second stage of surgery, the perforators were located again before surgery with the same method. The size of defects after the excision of facial scars ranged from 6 cm×4 cm to 18 cm×16 cm. With perforators used as nutrient vessels, narrow pedicle flaps or random flaps ranging from 6 cm×6 cm to 22 cm×18 cm were elevated as rotating or advancing to reconstruct the defects. The donor sites were sutured directly. Some of the flaps needed stage Ⅲ operation for cutting the pedicle. The survival of flaps, post-operation complications, and follow-up were assessed. Results: All flaps of 22 patients survived. All the donor sites were closed simultaneously. One patient underwent an additional surgery for 5 cm×4 cm necrosis on distal part of flap caused by subcutaneous hematoma. Two patients with epidermis blister on the flaps were healed by themselves after dressing change. Due to rapid expansion, blood capillary proliferation appeared on the central part of the flap in 3 cases, after slowing down the expansion speed properly, which had no impact on flap transfer. No ischemia or venous congestion phenomenon were observed in the other flaps. During follow-up of 5 to 48 months, the flaps of patients showed no significant bloated appearance, with good complexion and texture, and even could reproduce facial fine-grained expressions naturally. Conclusions: For the reconstruction of extensive burn scars in the face, expanded super-thin perforator flaps can not only acquire large and thin flaps with high matching degree surface skin defect, but also reproduce facial fine-grained expressions. It is a simple and safe method which conforms to the facial aesthetic standard.