ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.

ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.

With the rapid development of synthetic biology, genetic engineering, and molecular manipulation methods in recent years, microalgae, as representatives of microbial cell factories, have been widely used as hosts in the production of high-value bioproducts, such as oils, pigments, proteins, and biofuels, demonstrating promising prospects of application in biochemical energy, food and drugs, and environmental protection. Despite these advancements, the low production efficiency of microalgae limits their industrial application. In addition to strain improvement and culture condition optimization, the regulation by exogenous chemical additives serves as a promising optimization strategy. This method relies on straightforward phenotypic screening and circumvents the necessity for intricate understanding of molecular targets in the metabolic and catabolic pathways involved in the synthesis of bioproducts. It enables rapid yield increasing of high-value bioproducts from microalgae and obtaining the required phenotypes. Although studies have reported the use of alternatives means such as exogenous additives to improve the growth of microalgae and the yield of high-value bioproducts, the classification and summarization of the types, applications, targeted strains, and molecular mechanisms of these additives are not comprehensive. Here, we review the studies using chemical inducers or enhancers to improve cell growth and high-value bioproduct accumulation in microalgae in recent years. This paper focuses on the types of exogenous additives, the effects of exogenous additives and their combinations on microalgae growth and high-value bioproduct accumulation, and the molecular mechanisms of related effects. We aim to provide information for researchers to use methods of synthetic biology to develop suitable cell chassis and harness microalgae for industrial production.
Microalgae/drug effects* ; Biofuels

Objective:To investigate the application effect of case-based learning (CBL) based on the clinical case library of stomatology in standardized residency training for comprehensive stomatology.Methods:A total of 52 residents in Department of Stomatology, Chongqing Medical University, were given CBL teaching based on the clinical case library of comprehensive stomatology, and a questionnaire survey was performed to evaluate the teaching effect. Theoretical and skill assessments were performed before and after CBL teaching, and a comparative analysis was performed. SPSS 19.0 software was used for the t-test. Results:The questionnaire survey showed that CBL teaching based on the clinical case library of stomatology effectively improved the ability of independent learning [92.31% (48/52)], the interest in learning [88.46% (46/52)], and the ability for case diagnosis and the accuracy of investigation and judgment [94.23% (49/52)]. This method helped with the mastery and understanding of the theoretical knowledge in stomatology [96.15% (50/52)] and improved the abilities for expression and communication [84.62% (44/52)] and the ability to find and solve problems [94.23% (49/52)]. It also helped to stimulate the interest in scientific research and teaching [82.69% (43/52)] and create an active classroom atmosphere [82.69% (43/52)]. Among these residents, 94.23% (49/52) liked CBL teaching, and 88.64% (46/52) thought the setting of the case library was reasonable. After the application of CBL teaching, there were significant increases in theoretical score [from (66.74±4.25) points to (81.44±7.16) points] and skill examination score [from (64.00±3.14) points to (81.96±7.50) points].Conclusions:CBL teaching based on the case library of stomatology has a good teaching effect in the standardized residency training for comprehensive stomatology and can not only improve the theoretical and skill assessments of residents, but also improve their learning interest and clinical thinking ability.

Objective To observe the value of ultrasound-guided intra-articular injection of hypertonic glucose(HG)for treating knee osteoarthritis in plateau area.Methods Ninety-one patients with knee osteoarthritis in plateau area(124 affected knee joints)were enrolled.The knee joints were divided into 20％HG group(n=67),25％HG group(n=42)or sodium hyaluronate group(n=15)based on the medication.Clinical and ultrasound scores were compared before and after treatment,and the efficacy of injection of HG was evaluated.Results At the 12th and 48th weeks after treatment,visual analog scale(VAS)scores decreased in all 3 groups(all P＜0.05),and Lysholm scores of 20％HG group and 25％HG group increased compared to those before treatment(all P＜0.05).The difference of Lysholm score before and in the 12th week after treatment,and of VAS score before and in the 48th week after treatment of 25％HG group were higher than those of 20％HG group(both P＜0.05).The joint exudation score of 20％HG group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial blood flow score decreased in the 12th and 48th weeks after treatment compared to those before treatment(both P＜0.05).The joint exudation score of 25％HG group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial hyperplasia and synovial blood flow score decreased in the 12th and 48th weeks after treatment compared to before treatment(all P＜0.05).The joint exudation score of sodium hyaluronate group decreased in the 48th week after treatment compared to that before treatment(P＜0.05),and the synovial hyperplasia score decreased in the 12th and 48th weeks after treatment compared to that before treatment(both P＜0.05).Conclusion Ultrasound-guided intra-articular injection of HG,esp.25％HG,had certain value for treating knee osteoarthritis in plateau area.

Nipah virus(NipahVirus,NiV)is a zoonotic virus that can cause encephalitis and severe respiratory symptoms in humans and animals,and is at risk of being introduced into China.At present,there are many factors related to the transmission of Nipah virus disease(NVD),but the actual effects of these factors are controversial.Therefore,with the help of meta-analysis,this paper aims to determine the current mortality and the main means of transmission of NVD,so as to pro-vide reference for the input of controlling Nipah virus disease and making emergency plans for pre-vention and control in our country.By searching the articles published in Pubmed,Embase,Web of knowledge,CNKI,VIP Chinese Sci-tech Journals Database and Wanfang Database up to December 31,2022,the literature of cross-sectional,cohort and case-control studies with NiV encephalitis fa-tality rate(CFR)and risk factors were selected.Results showed that a total of 25 literatures were included in the meta-analysis after retrieval and screening,and the fatality rate of NiV encephalitis was 64.6％(95％CI,60.8-68.2;I2=96.8％).Subgroup analysis showed that tree climbing(OR=1.43;95％CI:1.05-1.96),bats were seen near their nighttime residence(OR=2.38;95％CI:1.74-3.25)and direct contact with date palm SAP(OR=6.01;95％CI:4.07-8.89)Bananas(OR=2.25;95％CI:1.31-3.85)OR porcine(OR=11.87;95％CI:1.15-122.23)was significantly associated with NiV encephalitis.The results of this study suggest that NiV encephalitis has a high mortality rate,and tree climbing,nocturnal exposure to bats,and exposure to pig,banana,and date palm SAP increase the risk of NiV encephalitis.In order to prevent NiV transmission,epidemic surveillance,education and publicity should be strengthened and protective measures should be taken.

OBJECTIVE To investigate the anti-pulmonary fibrosis effect of linarin in vivo and in vitro， and investigate its mechanism preliminarily. METHODS C57BL/6J mice were randomly divided into normal group （carboxymethylcellulose sodium）， model group （carboxymethylcellulose sodium）， positive control group （pirfenidone， 200 mg/kg）， linarin low-dose and high-dose groups （12.5， 25 mg/kg）， with 8 mice in each group. Except for normal group， pulmonary fibrosis model was induced in other groups. After modeling， they were given relevant medicine intragastrically， once a day， for consecutive 14 d. The general situation of mice was observed， and their lung indexes were measured； the levels of tumor necrosis factor-α （TNF-α） and transforming growth factor-β1（ TGF-β1） in serum and interleukin-6 （IL-6） in lung tissue were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the histopathological morphology of lung. The pulmonary fibrosis was scored according to Ashcroft score standard. The expressions of α-smooth muscle actin （α-SMA） and （type Ⅰ collagen， Collagen Ⅰ）， phosphorylated extracellular signal-regulated kinase （p-ERK1/2） and TGF-β1 in lung tissues were detected. HFL1 cells were stimulated by TGF- β1 to form pulmonary fibrosis model in vitro， which were divided into normal group， model group and linarin low-， medium- and high-concentration groups （3.7， 7.4， 14.8 mg/L）. After being cultured for 48 h， the protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 in HFL1 cells were detected. RESULTS In vivo， compared with normal group， the lung index of model group and the levels of TNF- α， TGF- β1 and IL-6 were significantly increased （P＜0.01）. There were a large number of inflammatory infiltration and cellular fibrosis lesions in the alveoli， and a large number of collagen depositions. The scores of HE staining and Masson staining were significantly increased （P＜0.01）. The protein expressions of α-SMA， Collagen Ⅰ， p-ERK1/2 and TGF-β1 in lung tissue were up-regulated significantly （P＜0.01）. Compared with model group， above indexes of mice were improved significantly in linarin high-dose group （P＜0.05 or P＜0.01）， and most of indexes （except for lung index） were improved significantly in linarin low-dose group （P＜0.05 or P＜0.01）. In vitro， compared with blank group， the density of cells in the model group increased， and obvious proliferation and other changes occurred； protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 were significantly up-regulated （P＜0.05 or P＜0.01）. Compared with model group， the cell density of each concentration group was decreased and the morphology gradually returned to normal； the expressions of above proteins in linarin high-concentration group and the protein expression of p-ERK1/2 in linarin medium-concentration group were down-regulated significantly（P＜0.05 or P＜0.01）. CONCLUSIONS Linarin may regulate ERK and inflammatory pathways to reduce the inflammatory response， thereby exerting anti-pulmonary fibrosis effect.

Objective:To investigate the clinical effect of a 3D reconstruction assisted preoperative optimal design of anterolateral abdomen cross-region free perforator flaps for repair of soft tissue defects of limbs.Methods:Twenty patients who were treated for soft tissue defects of hand, forearm, foot and ankle in the Department of Hand Surgery, the Sixth Hospital of Ningbo from October 2017 to January 2020 were included in this study. Among the patients,17 had soft tissue defects in hand and forearm and 3 with composite tissue defects including ankle and soft tissue defect of foot. The sizes of soft tissue defects in limbs ranged from 6 cm × 8 cm - 36 cm × 18 cm. Twenty free cross-area perforator flaps were optimal designed with CTA and 3D assisted reconstruction before surgery. Following combinations of flaps were designed: (1) Free perforator flap with inferior abdominal artery and superior abdominal artery; (2) Free perforator flap with superficial iliac circumflex artery and deep iliac circumflex artery; (3) Free perforator flap with superficial iliac circumflex artery and inferior abdominal wall perforator artery; (4) Free perforator flap with perforators of superficial iliac circumflex artery plus superficial abdominal artery; (5) Free perforator flap with perforating artery of lower abdominal wall and superficial artery of abdominal wall. The overall nutritional area of a combined flap were 272.3 cm 2± 12.5 cm 2, 107.4 cm 2± 9.3 cm 2, 193.6 cm 2± 24.2 cm 2, 155.2 cm 2± 20.1 cm 2 and 203.7 cm 2± 16.3 cm 2, respectively. All the donor sites were sutured directly in one stage. The appearance, texture, blood supply, colour, joint movement of affected limbs, recovery and function of donor sites were observed through postoperative follow-up visits at the outpatient clinic. Results:Among the 20 anterolateral transventral perforator flaps, 18 flaps survived successfully; One had partial necrosis after surgery, and healed after dressing change. Subcutaneous haematoma occurred in 1 flap, and survived after drainage. In this study, there was no postoperative infection of flap. A total of 19 flaps healed in one stage, except 1 that had a delayed healing and the flap wound was closed after dressing change for 1 week. According to Disability of Arm, Shouder and Hand (DASH) questionnaire evaluation, which is widely used in the world to evaluate the therapeutic effect after limb injury, combined with the 6-12 months of follow-up, the functional recovery of 17 patients with upper limbs iniury was 7 in excellent, 9 in good and 1 in poor. The overall excellent and good rate achieved 94.1%. All the 3 patients with foot injury recovered well, and the walking and jumping were not significantly affected. The results were all excellent according to the Maryland Foot Function Scoring. Sensation of flaps was evaluated according to the British Sensory Function Evaluation, it showed: 3 in S 2, 15 in S 3 and 2 in S 3+. All 20 flaps had good blood supply, in soft texture, good colour, feeling, thickness and movement. The donor sites all healed well. Conclusion:Combined with an optimal preoperative design, the perforator flap of anterior lateral wall cross-region can obtain a satisfactory clinical efficacy in repair of large area soft tissue defects. It is a feasible treatment method.

Pulmonary fibrosis is the end-stage manifestation of a large class of lung diseases characterized by fibroblast proliferation and accumulation of a large amount of extracellular matrix accompanied by inflammatory injury and tissue structure destruction. Studies have shown that flavonoids have anti-pulmonary fibrosis effects through multiple paths， including dihydromyricetin， morin and fisetin can inhibit fibroblast differentiation； Trollius altaicus flavonoids， hesperidin and linarin can play an anti-inflammatory role； total flavonoids from Scutellaria baicalensis， scutellarin and chrysin can inhibit epithelial- mesenchymal transition； total flavonoids of Litchi chinensis， diosmin and silybin can play an anti-oxidative stress role； quercetin， baicalin and apigenin can regulate autophagy； total flavonoids of Oxytropis falcata， calycosin and dihydroquercetin can regulate apoptosis； naringin， scutellarin and total flavonoids of Dracocephalum moldavica can inhibit pyroptosis， thus exerting anti- pulmonary fibrosis effects.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a specific subtype of the stiff-person syndrome, which is rare and difficult to diagnose clinically. A case of PERM in a 66-year-old female with a fluctuating progressive course was reported in this article. She had increased facial muscle tone, pruritus and sensory hypersensitivity mainly in the head and neck, medullary involvement syndrome and bilateral lower limb rigidity as the main clinical manifestations, and a previous history of pulmonary malignancy, thymoma, typeⅠ diabetes and Hashimoto′s thyroiditis. The patient′s serum and cerebrospinal fluid were positive for anti-glutamic acid decarboxylase antibody. The electromyogram showed a large number of motor unit potentials in the trunk and proximal extremities in the quiet state, which were significantly enhanced during spastic episodes, consistent with the electromyographic manifestations of stiff-person syndrome. The final diagnosis was PERM, and immunotherapy including gamma globulin and hormone responded well. PERM is a rare neurological autoimmune disease with atypical early symptoms, which can be easily misdiagnosed, and it requires attention to avoid delaying the diagnosis.