ObjectiveTo evaluate the larvicidal effect of ultrasonic waves against Aedes albopictus larvae at various exposure parameters (distance and time), and to preliminarily investigate the effects of different containers (water volume and depth) and ultrasonic devices on the larvicidal efficacy, so as to provide experimental evidence for the application of ultrasound-based mosquito control technology. MethodsUnder controlled laboratory conditions, two commercially available ultrasonic devices [40 kHz/300 W and (50±5) kHz/70 W] were used to systematically examine the effects of exposure distance (20, 40, 60, 80, and 100 cm), exposure duration (1, 3, 6, 15 and 60 min), larval instar(Ⅰ‒Ⅱ and Ⅲ‒Ⅳ）, and container type on the immediate mortality of Aedes albopictus larvae collected from urban areas of Shanghai. Statistical analysis of the mortality rates of larvae among different experimental groups was performed using the chi-square test. ResultsUltrasonic exposure exerted a detectable larvicidal effect against Aedes albopictus larvae of all instars. For early-instar larvae, exposure time significantly affected mortality at all tested distances (20, 40, 60, 80 and 100 cm), with χ² values ranging from 25.57 to 32.74 ( all P<0.001). No significant distance effect was observed in the first and second instar larvae after short-term exposure (1 and 3 min; P>0.05). However, a distance-dependent effect emerged from 6 min onward (P<0.05). During short-term exposure (1 min and 3 min) at close range (20 cm and 40 cm), the immediate mortality of the third and fourth instar larvae was higher than that of the first and second instar larvae. Conversely, during prolonged exposure (15 min and 60 min), the first and second instar larvae exhibited significantly higher mortality than that of the third and fourth instar larvae. These results indicated that larval mortality was jointly influenced by exposure duration and distance. Preliminary experiments indicated that larvicidal efficacy in shallow water was lower than that in deep water. No significant difference in larvicidal effect was observed between the two ultrasonic devices with different frequencies and power outputs. ConclusionUnder laboratory conditions, ultrasound can effectively kill Aedes albopictus larvae, and the larvicidal effect is jointly influenced by larval instar, exposure distance, and aquatic environment. Compact ultrasonic devices show potential for field application in biological mosquito control.

Shengyutang is a famous classical formula of tonic， which is made from Siwutang with Ginseng Radix et Rhizoma and Astragali Radix. It is included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. Based on the Principles of Key Information Research of Ancient Famous Classical Formulas， this paper used bibliometrics to sort out and research the key information of Shengyutang in the aspects of history， composition， origin and processing， dosage， decocting method， efficacy and indications. After research， it has been found that this formula was first recorded in Lanshi Micang written by LI Dongyuan during the Jin dynasty， composed of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix and Angelicae Sinensis taproot. The name of the formula passed down through generations was relatively unified， with clear origins and veins. In later generations， this formula was the mainstream， and adjustments were made to the dosage and composition according to the indication. In the formula， Astragalus membranaceus var. mongholicus was selected as the origin of Astragali Radix， and the origins of other medicinal materials were consistent with the 2020 edition of Chinese Pharmacopoeia. Except for Rehmanniae Radix Praeparata， the other medicinal materials were made from raw products， and the dosage form was boiled powder. According to the measurement standard in the Jin dynasty， the recommended usage and dosage were 1.24 g of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma each， 2.07 g of Astragali Radix and Angelicae Sinensis taproot each， crushed into coarse particles that pass through the 4 mesh sieve but can't pass through the 10 mesh sieve， added 1 200 mL of water and boiled to 300 mL， and removed the residue. Shengyutang has the functions of tonifying Qi and blood， and blood intake， treating various sores， and restlessness and insomnia caused by excessive blood flow. In ancient times， this formula was widely used in the treatment of surgical sores， gynecological diseases， deficiency syndrome， etc. In modern clinical practice， it is mostly used to treat gynecological， neurological， musculoskeletal， hematological diseases caused by Qi and blood deficiency. In this paper， the key information of Shengyutang was researched by reviewing relevant ancient literature， in order to provide reference for the modern application and development of this formula.

Objective To analyze the disease burden of early-onset colorectal cancer (EOCRC) at the global, regional, and national levels from 1990 to 2021, and to predict the disease burden trend from 2022 to 2026. Methods Based on the Global Burden of Disease (GBD) database, the incidence, mortality, and disability-adjusted life year (DALY) rate of EOCRC across 204 countries and regions from 1990 to 2021 were obtained. The time trends of these indicators were assessed by calculating the estimated annual percentage change (EAPC), and the contributions of ten risk factors to the EOCRC burden were analyzed. The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden from 2022 to 2026. Results From 1990 to 2021, the number of new global EOCRC cases increased from 107 310 to 211 890, with the incidence rising from 3.96 to 5.37 per 100 000 people. In 2021, global EOCRC incidence, mortality, and DALY rate increased with age; males had higher rates than females in terms of incidence, mortality, and DALY rate in all age groups. In 2021, East Asia had the highest number of new cases, deaths, and DALY. From 1990 to 2021, the global EAPC for incidence rate was 0.96%, and death rate was –0.38%. ARIMA model indicated that from 2022 to 2026, the global incidence of EOCRC would continue to rise, while mortality and DALY rate would be expected to decline. Conclusions The disease burden of EOCRC has significantly increased globally from 1990 to 2021, with notable regional, age, and sex differences. By 2026, the mortality and DALY rate of EOCRC will decline, while the incidence is expected to further increase, highlighting the urgency of taking active measures to address the growing trend of EOCRC.

Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

Objective:To evaluate the role of fibrinogen in perioperative neurocognitive disorder (PND) in aged mice.Methods:Sixty SPF healthy male C57BL/6J mice, aged 16-18 months, weighing 25-30 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), PND group (group P), urokinase group (group U) and PND+ urokinase group (group PU). Abdominal surgery was performed under 3% sevoflurane anesthesia to establish the mouse model of PND. In PU group, urokinase 20 000 U/kg was intraperitoneally administered at 1 h after surgery, once a day, for 5 consecutive days. In group U, urokinase was intraperitoneally injected once a day for 5 consecutive days without anesthesia and surgery. The cognitive function was assessed after operation using the novel object recognition test (discrimination index) and the Morris water maze test (frequency of crossing the original platform and percentage of the time spent in the target quadrant). The expression of occludin, claudin-5, fibrinogen and ionized calcium-binding adapter molecule 1 (Iba-1) and CD11b in hippocampal tissues was detected using Western blot, the area of fibrinogen extravascular deposits was measured and the morphology of microglia was observed using the immunofluorescence staining, and the mRNA expression of pro-inflammatory factors (interleukin-1beta, tumor necrosis factor-alpha, and inducible nitric oxide synthase), anti-inflammatory factors (interleukin-4 and arginase-1), and chemokines (chemokine 2 and chemokine ligand 10) in hippocampal tissues was detected by quantitative real-time polymerase chain reaction after surgery. Results:Compared with group C, the parameters of cognitive function were significantly decreased, the expression of occludin and claudin-5 was down-regulated, the expression of fibrinogen was up-regulated, the area of fibrinogen extravascular deposits was increased, the number of branches was decreased and the average process length was shortened in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was up-regulated, the mRNA expression of proinflammatory cytokines and chemokines was up-regulated, and the mRNA expression of the anti-inflammatory factors was down-regulated in group PND ( P<0.05). Compared with group PND, the parameters of cognitive function were significantly increased, the expression of occludin and claudin-5 was up-regulated, the expression of fibrinogen was down-regulated, the area of fibrinogen extravascular deposits was decreased, the number of branches was increased and the average process length was prolonged in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was down-regulated, the mRNA expression of proinflammatory cytokines and chemokines was down-regulated, and the mRNA expression of the anti-inflammatory factors was up-regulated in group PU ( P<0.05). Conclusions:Fibrinogen deposits in the brain parenchyma through the damaged blood-brain barrier after anesthesia and surgery and participates in the development of PND, and the underlying mechanism may be related to the promotion of microglial activation and the induction of neuroinflammation in aged mice.

Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) preventing sevoflurane-induced neurotoxicity and phosphorylated Tau glymphatic system clearance pathway in neonatal mice.Methods:Eighteen C57BL/6 pregnant mice were used in this study and subjected to 2 feeding regiments using the random number table method. Twelve mice were selected to receive a standard diet, and 6 mice were selected to receive a diet supplemented with fish oil (ω-3 polyunsaturated fatty acids [300 mg was added to every 20 g of standard diet from the 2nd day of gestation to 14 days after parturition). The healthy neonatal mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Forty-eight neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to control group (C group), 48 neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to sevoflurane group (S group), and 48 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS group) using the random number table method. All the offspring mice in all groups were breastfed until 21 days of birth and then were housed in separate cages from their mothers after 21 days of birth and provided with ad libitum access to standard food. S group and PS group inhaled 3% sevoflurane and 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen at the same flow rate. Y maze test was performed at postnatal day 33 to assess the spatial memory and cognitive function. The rotarod test was performed at postnatal day 35 to assess the fine motor coordination. The influx and efflux functions of the glymphatic system were assessed through intracisternal tracer infusion with the fluorescent tracer at postnatal days 14 and 35. The influx function was evaluated by the percentage of the area of tracer penetration 30 min after injection, while the efflux function was determined by the percentage of the residual area of the tracer 90 min after injection. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 14 for determination of the expression of phosphorylated Tau protein at serine 202 site and threonine 205 site (Tau-PS202/PT205) and total Tau protein by Western blot. The cerebrospinal fluid (CSF) was collected at postnatal day 14 for determination of the concentration of phosphorylated Tau protein by enzyme-linked immunosorbent assay. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 35 for determination of the expression of caspase-3, caspase-9 and cytochrome C (Cyt c) (by Western blot) and the apoptosis rate of neurons (by TUNEL).Results:Compared with C group, the time of staying at the new arm and in the rotarod test was significantly shortened, the percentage of new arm movement distance was decreased, the percentage of tracer penetration area was decreased at postnatal day 14, the percentage of residual tracer area was increased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was up-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was reduced at postnatal day 14, the apoptosis rate of hippocampal neurons was increased at postnatal day 35 ( P<0.05), and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was up-regulated at postnatal day 35 in S group ( P<0.05). Compared with S group, the time of staying at the new arm and in the rotarod test was significantly prolonged, the percentage of new arm movement distance was increased, the percentage of tracer penetration area was increased at postnatal day 14, the percentage of residual tracer area was decreased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was down-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was increased at postnatal day 14, the apoptosis rate of hippocampal neurons was decreased at postnatal day 35, and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was down-regulated at postnatal day 35 in PS group ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevents cerebral neurotoxicity induced by repeated neonatal sevofurane exposure may be related to the enhancement of phosphorylated Tau protein clearance via the glymphatic system.

Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) in preventing brain neurotoxicity caused by multiple sevoflurane anesthesia and peroxisome proliferator-activated receptor gamma (PPARγ)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) signaling pathway in neonatal mice.Methods:This study was performed in 2 parts. Part Ⅰ Using a random number table method, 6 C57BL/6 pregnant mice were assigned to receive a standard diet, 3 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition (ω-3 PUFAs 300 mg were added to every 20 g of conventional diet). Healthy C57BL/6 mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Seventeen neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to control group (C group), 17 neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to sevoflurane group (S group), and 17 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS1 group) using the random number table method. Part Ⅱ Four C57BL/6 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition. After parturition, 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS2 group), and 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus PPARγ inhibitor GW9662 plus sevoflurane group (PGS group) using a random number table method. GW9662 (2 mg/kg) was intraperitoneally injected at 30 min before exposure to sevoflurane in PGS group. All offspring mice were breastfed until 21 days of age, after which they were housed separately from the mother and allowed ad libitum access to a conventional diet. S, PS1, PS2 and PGS groups inhaled 3% sevoflurane in 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen instead. Y maze test was performed on days 33 after birth. The rotarod test was performed on day 35 after birth. After the behavioral testing, the expression of PPARγ, PGC1α, mitofusin-1 (MFN1), MFN2, dynamin-related protein 1 (DRP1), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and tumor necrosis factor-α (TNF-α) was detected by Western blot, the ultrastructure of mitochondria in hippocampal neurons was observed with a transmission electron microscope, and the mitochondrial membrane potential (MMP), level of reactive oxygen species (ROS) and content of ATP were determined.Results:Part Ⅰ Compared with C group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was down-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was up-regulated, the MMP and content of ATP were decreased, and the level of ROS was increased in S group ( P<0.05). Compared with S group, the time of stay at the new-arm and time spent on the rotarod were significantly prolonged, the percentage of movement distance in the new-arm was increased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was up-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was down-regulated, the MMP and content of ATP were increased, and the level of ROS was decreased in PS1 group ( P<0.05). Part Ⅱ Compared with PS2 group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the MMP and content of ATP were decreased, the level of ROS was increased, and the expression of IL-6, IL-1β and TNF-α was up-regulated ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevent brain neurotoxicity caused by multiple sevoflurane anesthesia is related to the activation of the PPARγ/PGC1α signaling pathway and alleviation of mitochondrial dysfunction and neuroinflammation in neonatal mice.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:To evaluate the effect of multiple sevoflurane anesthesia on the metabolism of long-chain fatty acids in the hippocampus of newborn mice and the role of peroxisome proliferator-activated receptor-beta (PPARβ).Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, weighing 3-5 g, were divided into 2 groups ( n=8 each) by a random number table method: control group (group C) and multiple sevoflurane anesthesia group (group S). This study was performed in 2 parts. PartⅠ Sixteen newborn mice were divided into 2 groups ( n=8 each) using a random number table: control group (C group) and multiple sevoflurane anesthesia group (S group). Anesthesia was performed with sevoflurane on postnatal days 6, 7 and 8. The hippocampus was obtained at postnatal day 9 for determination of the content of long-chain fatty acids (by ultra-high performance liquid mass spectrometry), expression of PPARβ (by Western blot), and expression of stearoyl-CoA desaturase-2 (Scd2) and fatty acid desaturase 2 (Fads2) mRNA (using quantitative real-time polymerase chain reaction). Part Ⅱ Twenty-one newborn mice were divided into 3 groups ( n=7 each) using a random number table: control+ normal saline group (group C+ S), sevoflurane + normal saline group (group S+ S), and sevoflurane+ PPARβ specific agonist KD3010 group (group S+ K). Anesthesia was carried out with sevoflurane on postnatal days 6, 7 and 8. KD3010 25 mg/kg was intraperitoneally injected once a day from postnatal day 6 to 13 in S+ K group. The novel object recognition test was performed on postnatal day 37, and the Morris water maze test was performed on postnatal day 42. The hippocampal tissues were obtained on postnatal day 47 for detection of the expression of Scd2 mRNA and Fads2 mRNA by fluorescent quantitative real-time polymerase chain reaction. Anesthesia was carried out with sevoflurane as follows: Mice were exposed to 3% sevoflurane in 40% oxygen-60% nitrogen in an induction chamber for 2 h at a flow rate of 1 L/min. Results:PartⅠ Compared with group C, the total content of long-chain fatty acids, contents of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids were significantly decreased, the percentage of saturated fatty acids was increased, the percentage of monounsaturated fatty acids and polyunsaturated fatty acids was decreased, the expression of Scd2 mRNA and Fads2 mRNA was down-regulated, and the expression of PPARβ was down-regulated in group S ( P<0.05). Part Ⅱ Compared with group C+ S, the discrimination index in the novel object recognition test and percentage of time spent in the target quadrant were significantly decreased, the number of crossing the original platform was reduced, and the expression of Scd2 and Fads2 mRNA was down-regulated in group S+ S ( P<0.05). Compared with group S+ S, the discrimination index in the novel object recognition test and percentage of time spent in the target quadrant were significantly increased, the number of crossing the original platform was increased, and the expression of Scd2 and Fads2 mRNA was up-regulated in group S+ K ( P<0.05). Conclusions:Multiple anesthesia with sevoflurane can lead to the disorder of long-chain fatty acid metabolism in the hippocampus of neonatal mice, resulting in long-term cognitive dysfunction. The mechanism may be related to inhibiting the activity of hippocampal PPARβ signaling pathway.

Objective:To evaluate the relationship between preoperative gut microbiota and post-operative ventilator-associated pneumonia (VAP) in patients undergoing coronary artery bypass grafting.Methods:This was a secondary analysis of a previous research project study. Patients who received invasive mechanical ventilation treatment after elective off-pump coronary artery bypass grafting at the Second Hospital of Hebei Medical University from April to September 2023 were selected and divided into VAP group and non-VAP group based on whether VAP occurred after surgery. Fecal samples were collected from patients before surgery, and 16S rRNA gene sequencing was used to analyze the characteristics of preoperative gut microbiota in the two groups. The differences in the diversity of gut microbiota between the two groups were compared. The linear discriminant analysis was used to identify the gut microbiota with significant differences between groups (differential bacteria), and logistic regression analysis was conducted to assess the association between differential bacteria and VAP. Receiver operating characteristic curves were drawn to analyze the predictive value of the differential bacteria for VAP.Results:A total of 79 patients were finally included, with 25 in VAP group and 54 in non-VAP group. The Beta diversity analysis showed statistically significant differences between VAP group and non-VAP group (pseudo- F=2.00, P=0.002). The linear discriminant analysis indicated that Bifidobacterium, Blautia and Megamonas were enriched in non-VAP group, while Klebsiella was enriched in VAP group. Multivariate logistic regression analysis showed that the relative abundance of Bifidobacterium was a protective factor for postoperative VAP ( OR=0.32, 95% confidence interval [ CI] 0.15-0.71, P=0.005), and the relative abundance of Klebsiella was a risk factor for postoperative VAP ( OR=2.49, 95% CI 1.143-5.43, P=0.022). The area under the receiver operating characteristic curve of the relative abundance of Bifidobacterium for predicting VAP was 0.80 (95% CI 0.69-0.90, P<0.001) and of the relative abundance of Klebsiella was 0.70 (95% CI 0.57-0.83, P=0.005). Conclusions:Bifidobacterium is a protective factor, while Klebsiella is a risk factor for postoperative VAP in patients undergoing coronary artery bypass grafting, and the relative abundance of both bacteria has a certain predictive value for VAP.