Abstract: Mosquitoes and mosquito-borne illnesses remain one of the major public threats which is intensified by the emergence and resurgence of new and existing vector species. Mosquito control is often the only sustainable measure to combat mosquito-borne diseases due to lack or limitation in vaccinations and/or effective medications. Among mosquito control interventions, larviciding to target aquatic habitats is more cost-effective and feasible as opposite to adulticiding which focuses on air-borne adult stages. The available mosquito larvicides are at a historical low owing to numerous reasons. Currently, available larvicides are based on microbial agents, insect growth regulators (IGRs), and a few others of botanical origins. In the IGR arena, juvenile hormone mimics have drawn a lot of attention in research, development, and application. Pyriproxyfen (PPF) was first developed in the early 1970s by Sumitomo Chemical Co. Ltd. (SCC). Its great potential and safety profile to control a wide variety of arthropod pests have been recognized ever since. The current review provides general information and highlights the following advantages of PPF: unique mode of action to mimic the action of natural juvenile hormone (JH) in mosquitoes, broad target spectrum against many mosquito species, the highest bioactivity against mosquitoes as compared with all other known or potential mosquito larvicides, low risk in resistance development and lack of cross-resistance with other larvicides studied, and high activity against species in Stegomyia group. Recently, more potential uses of PPF against adult mosquitoes in bait, barrier treatment, and bed net treatment have been on the horizon. Environmental concerns about PPF residues and their metabolites are also discussed. In general, PPF is one of the critical tools in combating mosquito species of public health importance for now and the foreseeable future.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization (MR) approach. Methods Summary data for exposure factors and outcome were obtained from different genome-wide association studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted (IVW) method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results. Results The random-effects model of IVW analysis showed that heel bone mineral density (OR=0.986;95% CI,0.974 to 0.998;P=0.023) as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density (OR=1.031;95% CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density (OR=1.014;95% CI,0.973 to 1.057;P=0.505),and forearm bone mineral density (OR=1.011;95% CI,0.935 to 1.094;P=0.775) as outcome datasets showed no causal effect with bronchial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results. Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone mineral density in patients with bronchial asthma to timely detect and intervene osteoporosis.

ObjectiveTo explore the clinical efficacy and safety of Qifu Yixin prescription in treating chronic heart failure in the patients with the syndrome of heart Qi deficiency， so as to provide clinical evidence for the treatment of chronic heart failure with this prescription and promote the clinical application and transformation of this prescription. MethodA total of 106 chronic heart failure patients with the syndrome of heart Qi deficiency who met the criteria in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine （TCM） from September 2022 to May 2023 were selected and randomized into an observation group （53 cases） and a control group （53 cases）. Both groups received routine Western medicine treatment. In addition， the observation group received Qifu Yixin prescription， while the control group received placebo. The treatment course for both groups was 12 weeks. The New York heart association （NYHA） cardiac function grading， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth-stimulating expression gene 2 （sST2）， left ventricular ejection fraction （LVEF）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， left ventricular end diastolic diameter （LVEDD）， TCM syndrome scores， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ）， and Kansas City Cardiomyopathy Questionnaire （KCCQ） were determined before and after treatment. ResultFinally， 102 patients were included for analysis， including 51 patients in the observation group and 51 patients in the control group. After treatment， 42 patients in the observation group showed improved cardiac function grading， with a total response rate of 82.35%， and 32 patients in the control group showed improved cardiac function grading， with a total response rate of 62.75%. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ²=4.923， P<0.05）. The observation group outperformed the control group in lowering the NT-proBNP level， elevating LVEF， decreasing the E/e' ratio （P<0.05）， reducing LVEDD and sST2 levels， and recovering TCM syndrome score， 6MWT score， MLHFQ score， and KCCQ score （P<0.05）. None of the safety indexes in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed. ConclusionQifu Yixin prescription can improve the heart function， exercise tolerance， and quality of life and alleviate the TCM syndrome of the chronic heart failure patients with the syndrome of heart Qi deficiency by inhibiting myocardial fibrosis.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective To make classification and segment measurement for the cases with tibiofibular and ankle fractures in parachuting landing, and investigate main classification types of parachuting fractures and fracture segments of high risk.Methods A total of 56 fracture cases in parachuting landing were collected, and the tibiofibula and ankle fractures were classified according to AO-OTA or Lauge-Hansen classification standards respectively based on their digital X-ray images. The medium plane between talus and tibia joint planes in ankle joint was defined as the reference plane. The highest and lowest injury points of tibia and fibula were marked respectively, and the fracture segment was defined between the highest and lowest point for statistical analysis.Results For tibiofibular and ankle fracture cases in parachuting landing, fracture at both tibia and fibula accounted for 80.4%. The major classification of tibiofibula fracture was 42-D/5.2 (45.8%) and 42-D/5.1 (16.7%). The major classification for ankle fracture was pronation-external rotation (PER, 59.4%) and supination-external rotation (SER, 37.5%). When tibiofibular and ankle fracture cases in parachuting landing occurred, the fracture segment of the tibia was mainly from 57 to 143 mm above the reference plane and from 6 mm below the reference plane to 24 mm above the reference plane, while the fracture segment of the fibula was 4-45 mm and 74-83 mm above the reference plane. Injury risks of all above segments were higher than 50%.Conclusions For protection of lower limbs in parachuting landing, the fracture at both tibia and fibula should be highly noticed. The ankle motion of PER and SER should be especially restricted in parachuting ankle protection.

BACKGROUND: The placental tissue structure is complex, including the amniotic membrane, chorion, and decidua from the mother. Mesenchymal stem cells derived from different tissues of the same placenta have been reported to have similar biological characteristics. To date, there is no study regarding quantitative comparison of differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. OBJECTIVE: To investigate the biological characteristics including differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. METHODS: The amnion-, chorion-, and decidua-derived mesenchymal stem cells were isolated from the placental tissue of a baby boy by enzymatic digestion method. The biological characteristics of these three kinds of mesenchymal stem cells were systematically investigated including cell morphology, immunophenotypes, karyotypeanalysis, adipogenic and osteogenic differentiation potential, and Treg cells proliferation capacity. RESULTS AND CONCLUSION: All three kinds of mesenchymal stem cells showed fibroblast-like morphology and expressed the surface markers of mesenchymal stem cells with high expressions of CD73, CD90 and CD105, as well as low expressions of CD14, CD19, CD34, CD45 and HLA-DR. The karyotypes of the amnion-and chorion-derived mesenchymal stem cells were the same as the fetus, and decidua-derived mesenchymal stem cells had the same karyotype as the mother. There were significant differences in adipogenic differentiation capacity between three kinds of mesenchymal stem cells (amnion-derived mesenchymal stem cells> chorion-derived mesenchymal stem cells> decidua-derived mesenchymal stem cells; P < 0.05). In contrast, the osteogenic differentiation capacity of amnion-derived mesenchymal stem cells was remarkably higher than that of decidua-derived mesenchymal stem cells (P < 0.05). The amnion-and chorion-derived mesenchymal stem cells had the higher potential of Treg cell proliferation induction than decidua-derived mesenchymal stem cells. These findings indicate that three sources of human placenta-derived mesenchymal stem cells have different karyotypes, adipogenic and osteogenic differentiation potential, and immunomodulatory capability, providing a variety of ideal seed cell sources for disease treatment.

Objective To probe the reasonable range of central lymph node dissections(CLNs)for papillary thyroid carcinoma (PTC) in cN0 T1/T2 by analyzing the metastasis regulations of PTC in cN0 T1/T2.Methods Data of 891 PTC patients in cN0T1/T2 cases according to the research criterion from Oct.2013 to Sep.2017 were analyzed.All the patients were under the treatment of the same group of surgeons in Department of Thyroid Surgery of the First Affiliated Hospital of the Kunming Medical University and had undergone operation of bilateral total resection of thyroid gland and central lymph node.The clinical and pathological data were collected.Univariate and multivariate analysis were used to investigate the risk factors of central neck lymph node metastasis and high volume central neck lymph node metastasis.Results ①Univariate analysis showed that gender (P=0.002),age(P=0.002),multiform(P=0.000),nodular goiter(P=0.000)and with Hashimoto's(P=0.031)had significant influence in prevalence of CLN node metastasis.Gender(P=0.010)and tumor size(P=0.000)showed significant influence in prevalence of high volume CNL node metastasis.In multivariate analysis,age (OR=0.962,OR=2.856)and nodular goiter(OR=0.969,OR=3.012)showed the independent risk factor of CNL node metastasis and high volume CNL node metastasis.②The numbers of lesion in unilateral lesion were not correlated with IpsiCLNs and Cont-CLNs metastasis (P=0.347,P=0.653).The tumor diameter was correlated with Ipsi-CLNs and ContCLNs metastasis (P=0.010,P=0.000).The tumor diameter of bilateral multifocal carcinoma was correlated with LN-prRLN-CLNs metastasis (P=0.019).The tumor diameter of left and right unilateral single focal lesion was not correlated with LN-prRLN-CLNs metastasis(P=0.684,P=0.072).Conclusions According to the study,it is recommended that the PTC in cN0 T1/T2 should routinely undergo preventive central lymph nodes dissection in the case of technical support:①Preventive overall CLND is recommended for unilateral non-microscopic carcinoma and bilateral multiform carcinoma,especially in those older than 55.②For patients with unilateral single or multifocal microscopic carcinoma,only ipsilateral central lymph nodes dissection can be considered.③ Generally,routine dissection is not necessary for the lymph nodes of the right recurrent laryngeal nerve in the central region of the neck.However,for bilateral non-small cancers and right non-small cancers,LN-prRLN-CLNs dissection is recommended.

Objective To investigate the pressing time and puncture site bleeding after extubation of superficial venous catheter in elderly patients.Methods Four hundred elderly inpatients were selected from respiratory department during June 2015 and December 2015 and were divided into two groups:200 patients as experimental group with pressing time of 5-6 minutes and 200 patients as control group with pressing time of 3-4 minutes.The same group of nurses pressed the puncture site after extubation and changes on skin and vessels were observed,which was to find out the optimal pressing time after extubation of superficial venous catheter in elderly patients.Results The presence of bleeding,bruising,success rate of the second puncture,swelling,pain and degree of comfort were compared between two groups and significant differences were found (P＜0.05).Conclusion Compared with those in control group,less bleeding,bruising,swelling,and pain,higher success rate of the second puncture and lower degree of comfort were found in experimental group.

Objective To investigate the expression of hsa-miR-144 in esophageal squamous cell carcinoma, and its relationship with clinicopathological features and prognosis. Methods Reverse transcriptase polymerase chain reaction (RT-PCR) method was used to detect the hsa-miR-144 in 46 cases of esophageal squamous cell carcinoma and adjacent normal tissue. The expression of hsa-miR-144 in esophageal squamous cell carcinoma and its difference in the clinicopatho?logical characteristics including gender, age, and tumor size were investigated. The relationship between the expression of hsa-miR-144 and prognosis of patients with esophageal squamous cell carcinoma was analyzed. Kaplan-Meier method and Log-rank test were used to analyse the differences in survival rates in different pathological characteristics. Results The ex?pression level of hsa-miR-144 was lower in esophageal squamous cell carcinoma 0.97(0.22-24.48)×10-6 than that of adjacent normal tissue 8.60(0.09-258.20)×10-6, the difference was statistically significant (Z=2.221, P<0.05). The expression level of hsa-miR-144 was higher in esophageal squamous cell carcinoma with no lymph node metastasis than that in esophageal squa?mous cell carcinoma with lymph node metastasis (Z=2.758,P<0.05), and the expression level decreased with the increase in the pathological staging (Z=7.737,P<0.05). There were no significant differences in the expression levels of hsa-miR-144 between different gender, age, tumor size, tumor location, tumor differentiation and tumor invasion depth (all P>0.05). There was no correlation between the expression of hsa-miR-144 and prognosis in patients with esophageal squamous cell carcino?ma (rs=0.031, P=0.839). In the survival rate, there was no statistic significance between high expressive of hsa-miR-144 group and low expressive group (P=0.828). The survival rate was lower in patients with lymph node metastasis than that of pa?tients without lymph node metastasis. The survival rates were lower in patients with relatively deep invasion and higher patho?logic stage (P<0.05). Conclusion The expression of hsa-miR-144 is down regulated in esophageal squamous cell carcino?ma, and which is associated with lymph node metastasis and pathological staging of esophageal carcinoma. It shows that hsa-miR-144 may serve as an anti-oncogene in the occurrence and development of esophageal squamous cell carcinoma.