The shaoyang meridian is an important pivot between the internal organs and meridians system， with the functions of regulating qi and blood， balancing yin and yang， and coordinating the ascending and descending movement of qi. Dysfunction of the shaoyang pivot can lead to spleen and kidney deficiency， impaired liver and gallbladder qi regulation， and stagnation of qi and blood. It is believed that the onset and progression of Crohn's disease are closely related to shaoyang pivot dysfunction， with the core pathogenesis characterized by shaoyang disharmony， spleen deficiency， dampness retention， and blood stasis. Based on this understanding， the treatment principle centers on harmonizing the shaoyang pivot， supplemented by methods such as warming and nourishing the spleen and stomach， tonifying shaoyang， and soothing the liver and benefiting the gallbladder. Acupuncture is employed to target key acupoints along the shaoyang meridian to restore its regulatory functions， improve spleen and stomach transformation and transportation， facilitate liver and gallbladder qi flow， and promote the circulation of qi and blood. This provides a practical therapeutic approach for acupuncture-based treatment of Crohn's disease.

OBJECTIVE To investigate the protective effect of artesunate(Art)against apoptosis and mitophagy induced by NaF in osteocytes MLO-Y4,and to explore the molecular mechanism.METHODS MLO-Y4 cells were treated with NaF(2 mmol·L-1)for 48 h to establish an in vitro model of osteocytes injuries,and the cells were divided into the cell control group,NaF(2 mmol·L-1)group and NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups.The cells were pretreated for 2 h and NaF was added for 48 h.The cell survival of MLO-Y4 cells was detected by MTT assay.The cell viability of MLO-Y4 cells was measured by Calcein-AM staining.The lactate dehydrogenase(LDH)content in the supernatant was examined by the LDH detection kit.The level of intracellular reactive oxygen species(ROS)was examined by DCFH-DA staining.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were detected by chemical colorimetry.Apoptosis was measured by Hoechst33342 staining and Annexin-V/PI staining.The level of mitochondrial membrane potential(MMP)was measured by JC-1 staining.The formation of autophagic vacuoles and morphological mitochondrial changes were observed via Lyso-tracker staining and Mito-Tracker staining.The ATP content was detected with the luciferase method.The expression of microtubule-associated protein light chain 3(LC-3)in mitochon-dria was examined by immunofluorescence staining.Protein expressions of LC-3,P62,E3 ubiquitin-ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)were detected by Western blotting.RESULTS Compared with the cell control group,the cell survival rate and cell viability were significantly reduced in the NaF group(P<0.01),LDH content in the supernatant,the level of intracellular ROS,the MDA content,apoptosis rate and autophagic vesicle formation were remarkably increased(P<0.01),protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly upregulated along with the elevation of LC-3 in damaged mitochondria(P<0.01),while P62 levels,SOD activity,MMP and ATP contents were reduced in NaF cells(P<0.05,P<0.01).Compared with NaF group,the cell viability and survival rate of MLO-Y4 cells in NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups were significantly increased(P<0.01);the content of LDH in supernatants was decreased obviously(P<0.01);the levels of intracellular ROS and MDA content were markedly reduced(P<0.05,P<0.01);the apoptosis rate and autophagic vesicle formation were remarkably decreased(P<0.05,P<0.01);protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly down-regulated along with the accumulation of LC-3 in damaged mitochondria(P<0.01);MMP and ATP content were also reduced(P<0.05,P<0.01);while SOD activityand P62 levelwere significantly increased(P<0.05,P<0.01).CONCLU-SION Art has a protective effect against oxidative damage induced by NaF in MLO-Y4 cells,which might be related to the inhibition of apoptosis and mitophagy.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Two patients with eyelid defect were admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University.Case 1 was a 45-year-old male with full layer eyelid defect after operation of lower eyelid pigment basal cell carcinoma. And case 2, male, 84 years old, had full eyelid defect after operation of recurrent basal cell carcinoma. A 3.0 cm×3.5 cm mucoperiosteal composite flap was designed in the longitudinal radian of the anterior and posterior palatal respectively. The flap was cut obtuse and sharp under the periosteum, and trimmed according to the shape of the eyelid defect. The flap was transplanted to the defect area of the posterior layer to replace the tarsus, palpebral and bulbar conjunctiva. The superficial outlet point of the zygomatic orbital-buccal lateral perforator vessels was explored before surgery, and the perforator flap was designed. The length and width of the flap were adjusted according to the eyelid defect during surgery, and the pedicle fascia perforator vessels were retained. The lower eyelid was 90°, and the upper eyelid was transferred nearly 100° to cover the outer skin and soft tissue defects of the upper and lower eyelids. The perforator flap was completely survived 9-12 days after the operation. After 8 months to 2 years and 8 months of follow-up, the upper and lower eyelid function and appearance were good, the original vision was maintained, and the cancer did not recur.

Two patients with eyelid defect were admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University.Case 1 was a 45-year-old male with full layer eyelid defect after operation of lower eyelid pigment basal cell carcinoma. And case 2, male, 84 years old, had full eyelid defect after operation of recurrent basal cell carcinoma. A 3.0 cm×3.5 cm mucoperiosteal composite flap was designed in the longitudinal radian of the anterior and posterior palatal respectively. The flap was cut obtuse and sharp under the periosteum, and trimmed according to the shape of the eyelid defect. The flap was transplanted to the defect area of the posterior layer to replace the tarsus, palpebral and bulbar conjunctiva. The superficial outlet point of the zygomatic orbital-buccal lateral perforator vessels was explored before surgery, and the perforator flap was designed. The length and width of the flap were adjusted according to the eyelid defect during surgery, and the pedicle fascia perforator vessels were retained. The lower eyelid was 90°, and the upper eyelid was transferred nearly 100° to cover the outer skin and soft tissue defects of the upper and lower eyelids. The perforator flap was completely survived 9-12 days after the operation. After 8 months to 2 years and 8 months of follow-up, the upper and lower eyelid function and appearance were good, the original vision was maintained, and the cancer did not recur.

Objective To investigate the effects of propofol combined with nalbuphine on diaphragmatic movement monitored by ultrasound in patients undergoing colonoscopy.Methods Forty patients, males 21 and females 19, aged 18-65 years, BMI 18-25 kg/m2, ASA physical status I or II, were recruited and scheduled to undergo elective painless colonoscopy.All patients were randomly divided into two groups (n =20):propofol group (group P) and propofol combined with nalbuphine group (group F).Patients in group F received nalbuphine 0.1 mg/kg intravenously 1 min before propofol administration, and patients in group P received same volume of normal saline.Propofol was infused by TCI and the initial target plasma concentration was set at 2μg/ml in all patients.The target concentration was adjusted gradually until the Ramsay sedation score reached 5.Then colonoscopy was started.During the colonoscopy, the propofol concentration was adjusted according to the Ramsay score.Ultrasound was used to monitor the movement of the right diaphragm of the patients.SpO2, MAP, HR, PETCO2, RR, diaphragmatic movement (DM), diaphragmatic thickness at the end of inspiration (TEI) and diaphragmatic thickness at the end of expiration (TEE) were recorded under calm breathing after entering the room (T0), Ramsay sedation score 5 points after propofol administration (T1), and Ramsay sedation score 2 after endoscopy (T2).The diaphragmatic thickening fraction (DTF) was calculated:DTF= (TEI-TEE) /TEI.Adverse reactions such as bradycardia, hypotension, body movement, and respiratory depression were recorded.Results Compared with T0, MAP, SpO2, HR and RR decreased, and PETCO2 increased at T1 time point in patients of the two groups (P<0.05).Compared with group F, the dose of propofol increased in group P (P<0.05).DM at T1 and T2, DTF at T1 were obviously higher in group F than those in group P (P<0.05).There were two cases had body movement in group P, and one case had bradycardia in group F.There was no case suffered from hypotension, respiratory depression and reflux aspiration in two groups.Conclusion Compared with propofol alone, propofol combined with nalbuphine can attenuate the dysfunction of the diaphragm.

Objective To evaluate the efficacy of injecting drugs through fiberoptic bronchoscope (FOB) and epidural catheter in improving topical anesthesia for awake tracheal intubation in patients undergoing cervical surgery.Methods Fifty patients with cervical spine injury that requiring surgical treatment,aged 18-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,were divided into 2 groups (n=25 each) using a random number table method:FOB injection hole group (group Ⅰ) and FOB combined with epidural catheter group (group Ⅱ).In group Ⅰ,2％ lidocaine was sprayed through the FOB injection hole on the oropharynx posterior (2 ml),glottis above vocal cords (3 ml) and the site 5 cm below the glottis (2 ml).In group Ⅱ,2％ lidocaine was sprayed via the epidural catheter implanted through FOB injection hole on the oropharynx posterior (1 ml),the site above vocal cords (3 ml),the site immediately after crossing the glottis (1 ml),the site 5 cm below the glottis (1 ml),and 2％ lidocaine 1 ml was slowly injected into the site 5 cm below the glottis to protuberance via the epidural catheter.Awake nasotracheal intubation was then performed under FOB guidance at 5 min after administration in both groups.When patients presented with severe bucking during operation and did not tolerate severe bucking,the previous procedure was repeated for rescue.When severe bucking was not significantly improved after carrying out rescue measures,thyrocricoceniesis was performed and the patients were tracheally intubated.The development of hypertension,tachycardia and hyoxemia was recorded during anesthesia and intubation.The operation time,intubation time,success of intubation at first attempt,requirement for rescue measures and thyrocricocentesis were recorded.The development of bucking,body movement and laryngeal spasm were record during anesthesia and tracheal intubation.JOA score was used to evaluate the occurrence of accentuated spinal cord injury after intubation.Parents' satisfaction with intubation was recorded and scored on 2nd day after operation.Results Compared with group Ⅰ,the incidence of hypertension and tachycardia was significantly decreased,the operation time was prolonged,the requirement for rescue measures and incidence of thyrocricocentesis were decreased,the incidence of body movement and bucking was decreased,and the parents' satisfaction scores were increased (P＜0.05),and no significant change was found in intubation time,success rate of intubation at first attempt or incidence of hyoxemia in group Ⅱ (P＞0.05).Accentuated spinal cord injury or laryngeal spasm was not found in either group.Conclusion Injecting drugs through FOB and epidural catheter can achieve better efficacy of topical anesthesia for awake tracheal intubation with reduced adverse reactions than injecting drugs through FOB injection hole in patients undergoing cervical surgery.

Objective To evaluate the effect of exogeneous adiponectin on hippocampal advanced glycation end products (AGEs)-reactive oxygen species (ROS)-endoplasmic reticulum stress (ERS) pathway in aged mice with postoperative cognitive dysfunction (POCD).Methods Thirty-two healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), POCD group, exogeneous adiponectin group (group APN), and vehicle group (group Veh).Splenectomy was performed to establish the POCD model in aged mice anesthetized with intraperitoneal pentobarbital sodium.In group APN, adiponectin 0.1 μg/g (in 2 μl of phosphate buffer solution) was injected into the lateral cerebral ventricle at 30 min before establishing the model.Phosphate buffer solution 2 μl was given at 30 min before establishing the model in group Veh.Cognitive function was assessed on day 7 after surgery.The mice were then sacrificed, and the hippocampus was harvested for determination of the area of AGE deposition (by immunohistochemistry), levels of ROS (by flow cytometry), and levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12 and ROS (using Western blot).Results Compared with group S, the freezing time in the contextual fear conditioning test was significantly shortened, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were increased, and the level of GRP78 was decreased in POCD, APN and Veh groups.Compared with POCD and Veh groups, the freezing time in the contextual fear conditioning test was significantly prolonged, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were decreased, and the level of GRP78 was increased in group APN.Conclusion Exogeneous adiponectin decreases the occurrence of POCD probably by blocking hippocampal AGEs-ROS-ERS pathway in aged mice.

Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups (n =40 each) using a random number table:sham operation group (group S),cecal ligation and puncture (CLP) group and lovastatin group (group L).Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5％ CMC (the solvent) was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations,white blood cell (WBC) count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA).Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR),and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.