Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.

Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.

Objective:To evaluate the current status of alpha-fetoprotein (AFP) detection, a comparability analysis was conducted on the results measured by eight automated immunoassay systems, incorporating external quality assessment (EQA) data from the Beijing Center for Clinical Laboratories (BCCL) for the years 2020, 2021, and 2023.Methods:Methodological evaluation. Abbott Architect i2000, Beckman DxI 800, Roche Cobas E601, Diasorin Liaison XL, Maccura IS1200, Autolumo A2000, Leadman CI1000, and Mindray CL-2000i were used to detect 40 individual AFP serum samples that were collected from the laboratory of Beijing Chaoyang Hospital in 2019. The AFP results from eight different systems were compared with the median cohort. Passing-Bablok regression was used to evaluate the correlation between methods, and the concordance correlation coefficient was used to analyse the consistency between methods. Taking the optimal biological variability (±5.90%) as the criterion for bias evaluation, the bias between systems was evaluated using Bland-Altman analysis. The EQA results for AFP from BCCL over the past three years were statistically analysed to calculate the robust mean, robust coefficient of variation ( CV), and standard uncertainty within groups. The acceptance limit is based on the requirement of desirable biological variability (±21.87%) of allowable total error, and the pass rates were calculated for instrument or method groups, respectively. Results:The CVs of the eight detection systems were all≤1/3 allowable total error (±8.3%), passing the precision verification. The average relative biases between two detection systems (Roche Cobas E601 and Maccura IS1200) and the median cohort were>±5.90%, while the other six detection systems were<±5.90%. The eight detection systems showed good correlation and consistency with the median cohort (both R2 and concordance correlation coefficients>0.95). The results of EQA showed that there were no statistically significant differences in the robust means within each instrument or method group ( P>0.05). In the instrument group, except for Siemens and two other groups, the robust CVs of other groups were within 9%. The pass rates of most instruments and methods after being grouped were higher than the total pass rate, but that of the enzyme immunoassay chemiluminescence method was relatively low. Conclusions:The eight automated AFP immunoassay systems show a good correlation with the median cohort, and the consistency of AFP detection results is satisfactory among most detection systems. However, the comparability of AFP detection results for certain systems needs further improvement.

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Background Domestic waste classification is one of the major livelihood projects in China. With the introduction of the Shanghai Household Waste Management Regulation in 2019, the work of domestic waste classification has been carried out nationwide, yet its potential risks especially those derived from microorganisms are not clear. Objective To investigate the microbial characteristics of the domestic waste in typical residential areas in Shanghai, and provide a theoretical basis for health protection during the domestic waste classification process in Shanghai and throughout China. Methods Dry and wet waste from a typical residential community in Shanghai were collected during 2019–2020. Microbial colonies were counted in domestic waste and analyzed for growth patterns. Then through 16S rRNA sequencing using lllumina PE250, hierarchical clustering analysis was conducted to reveal the similarity and dissimilarity of community compositions in different domestic waste groups, alpha diversity was estimated to reflect the richness and diversity of bacterial communities, principal co-ordinates analysis of unweighted UniFrac distance was performed to estimate the beta diversity, and linear discriminant analysis effect size (LEfSe) was used to find features differentially represented among domestic waste groups. Results In the chosen typical residential community of this study, the numbers of microorganisms in waste were quite different, with lower numbers of microorganisms in dry waste than the numbers in wet waste. In addition, different growth curves of microorganisms were shown for different seasons, and the peak baterial colony numbers were 200 CFU·cm⁻², 6×10⁵ CFU·mL⁻¹, 10 CFU·cm⁻², and 2×10⁶ CFU·mL⁻¹ for summer dry waste, summer wet waste, winter dry waste, and winter wet waste, respectively. The results of 16S RNA demonstrated significant differences in α and β diversity indicators among different waste groups, and the difference in waste classifications was larger than the difference of the same classification of waste in different seasons. The main compositions of bacterial colonies in domestic waste was Proteobacteria, followed by Firmicute and Bacteroidota. The clustering analysis showed that the microbial composition in summer dry waste was close to that in winter dry waste, while other groups were quite different. In total 48 differential bacterial taxa were found at the level of genus including Pseudomonas and Pantoea. Conclusion Different seasons and different classifications of domestic waste present varied microbial characteristics, with different potential pathogenic microorganisms. Together with other related studies, we suggest that different measures should be taken for different domestic wastes to prevent and control the health hazards associated with waste classification.

Scientific misconduct of researchers causes great waste of academic resources and academic life, which is not only related to the vigorous development of a country’s scientific undertaking, but also directly affects the reputation of the country in the field of scientific research. Based on the analysis of the causes of scientific misconduct of medical researchers in China, this paper comprehensively summarized a series of mature experiences of extraterritorial medical field in preventing scientific misconduct, and put forward corresponding and reasonable countermeasures and suggestions for China’s scientific research governance from three aspects: establishing an effective governance structure based on the normative framework, clarifying the definition standards of scientific research dishonesty in laws and regulations, and formulating good prevention procedures in a healthy academic environment, in order to promote the healthy development of scientific research in China’s medical field and further promote the innovation and progress of medical science and technology.

L-asparaginase hydrolyzes L-asparagine to produce L-aspartic acid and ammonia. It is widely distributed in microorganisms, plants and serum of some rodents, and has important applications in the pharmaceutical and food industries. However, the poor thermal stability, low catalytic efficiency and low yield hampered the further application of L-asparaginase. In this paper, rational design and 5' untranslated region (5'UTR) design strategies were used to increase the specific enzyme activity and protein expression of L-asparaginase derived from Rhizomucor miehei (RmAsnase). The results showed that among the six mutants constructed through homology modeling combined with sequence alignment, the specific enzyme activity of the mutant A344E was 1.5 times higher than the wild type. Subsequently, a food-safe strain Bacillus subtilis 168/pMA5-A344E was constructed, and the UTR strategy was used for the construction of recombinant strain B. subtilis 168/pMA5 UTR-A344E. The enzyme activity of B. subtilis 168/pMA5 UTR-A344E was 7.2 times higher than that of B. subtilis 168/pMA5-A344E. The recombinant strain B. subtilis 168/pMA5 UTR-A344E was scaled up in 5 L fermenter, and the final yield of L-asparaginase was 489.1 U/mL, showing great potential for industrial application.
Asparaginase/genetics* ; Bacillus subtilis/genetics* ; Industrial Microbiology ; Protein Engineering ; Rhizomucor/enzymology* ; Sequence Alignment

Objective:To investigate the relationship between serum sterol regulatory element binding protein-1 (SREBP-1) , serum amyloid P (SAP) and endocrine metabolism in patients with polycystic ovary syndrome.Methods:75 patients with polycystic ovary syndrome (study group) and 70 healthy women (control group) admitted to the First People’s Hospital of Yuhang District from Mar. 2018 to Feb. 2020 were enrolled. Various indexes were detected in both groups, including body mass index (BMI) , SREBP-1, SAP, triglyceride (TG) , total cholesterol (TC) , high-density lipoprotein (HDL-C) , and low-density lipoprotein (LDL-C) , fasting blood glucose (FBG) , fasting insulin (FINS) , and insulin resistance index (HOMA-IR) . The study group was further divided into two subgroups according to BMI, overweight group and normal group. SREBP-1 and SAP were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between SREBP-1, SAP, blood lipid index, blood glucose index and BMI in patients with polycystic ovary syndrome.Results:The body weight and BMI index of study group were higher than those of control group [ (72.23±4.84) kg vs (58.23±3.25) kg, (25.02±2.75) kg/m 2 vs (22.11±1.34) kg/m 2, P<0.05]. The levels of serum SREBP-1 and SAP in the study group were significantly higher than those in the control group [ (334.78±32.06) pg/ml vs (206.34±25.71) pg/ml, (206.34±25.71) mg/U vs (39.16 ±0.58) mg/U, P<0.05]. The expression levels of TG, TC, LDL-C, FBG, FINS, and HOMA-IR in the study group were higher than those in the control group [ (2.32±0.71) vs (1.53±0.52) , (4.85±0.54) vs (3.41±0.66) , (3.06±0.75) vs (2.11±0.89) , (6.45±0.62) vs (5.59±0.76) , (16.14±1.03) vs (13.02±1.34) , (1.67±0.38) vs (1.18± 0.26) , P<0.05]; HDL-C expression level in the study group was lower than that in the control group [ (1.43±0.56) vs (1.71±0.42) , P<0.05]. The levels of SREBP-1 and SAP in overweight group were higher than those in normal group [ (339.19±27.63) pg/ml vs (281.67±20.18) pg/ml, (53.26±0.59) mg/U vs (42.48±0.67) mg/U, P<0.05]. Serum SREBP-1 and SAP in the study group were positively correlated with TG, TC, LDL-C, HOMA-IR, and BMI, and were negatively correlated with HDL-C ( P<0.05) . Conclusion:SREBP-1 and SAP levels are elevated in patients with polycystic ovary syndrome, which are significantly correlated with TG, TC, LDL-C, HOMA-IR, BMI, and HDL-C, and can cause endocrine disorder by affecting glucose and lipid metabolism.

Objective To compare the hemostatic safety and efficacy of a new butterfly femoral artery compression device (FACD) with those of manual compression (MC) in patients undergoing percutaneous peripheral endovascular interventions via femoral artery. Methods A total of 283 patients, who received percutaneous endovascular interventions via femoral artery during the period from September 2016 to December 2017, were enrolled in this study. After endovascular intervention, 167 patients received FACD to make hemostasis (FACD group), and 116 patients received MC hemostasis (MC group) . The patient's comfortableness, time used for hemostasis (min), limb immobilization time (h), and the incidence of vascular complications in both groups were analyzed. Results All 283 patients were included in analysis, the results indicated that the hemostatic success rates in FACD group and MC group were 96.4％ (161/167) and 94.0％ (109/116) respectively, the difference between the two groups was not statistically significant (P>0.05) . The postoperative Kolcaba Comfort Scale score of FACD group was (85.0 ±11.2) points, which was remarkably higher than (58.4±11.7) points of MC group (P<0.05), the time used for hemostasis in FACD group was (9.2 ±2.2) min, which was strikingly shorter than (18.5 ±2.9) min in MC group (P <0.05) . The limb immobilization time in FACD group was (10.4±2.4) hours, which was obviously shorter than (23.1±4.1) hours in MC group (P <0.05) . The incidence of vascular complications in FACD group was 3.6％, which was dramatically lower than 9.5％ in MC group (χ2=4.206, P=0.04) . Conclusion The use of the new butterfly FACD can promptly, safely and effectively stop bleeding of femoral artery puncture site. The new butterfly FACD is superior to MC in shortening hemostatic time and limb immobilization time, in reducing incidence of vascular complications, as well as in improving patient's comfortableness degree.

Farnesoid X receptor ( FXR) plays a key role in me-tabolism of substance, such as bile acid, lipid, glucose,( etc) . Newly published credible discoveries have claimed that as a reg-ulatory hub in metabolism, FXR is closely linked with diverse chronic liver diseases, including viral hepatitis, alcoholic fatty liver disease, nonalcoholic fatty liver disease, hepatic fibrosis and hepatocellular carcinoma. This review summarizes the roles and mechanisms of FXR during the courses of chronic liver dis-eases, aiming at providing novel insights and therapeutic target for antifibrotic research and drug development.