ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

ObjectiveTo observe the clinical effectiveness of point ligation therapy combined with catgut embedment in acupoint for patients with refractory facial paralysis， and to explore the possible mechanisms from the perspective of neurotrophic factors. MethodsTotally 168 patients with intractable facial paralysis were randomly divided into point ligation plus catgut embedment group and electroacupuncture group， with 84 cases in each group. Both groups took methylcobalamin tablets orally， on the basis of which the point ligation plus catgut embedment group gave point ligation therapy at Quanliao （SI 18）， Dicang （ST 4）， Jiache （ST 6）， and catgut embedment in the local acupoints on the affected side combined with the distal acupoints， and the point ligation therapy combined with catgut embedment in acupoint was performed once every 30 days for three treatments； the electroacupuncture group took the same acupoints and gave electroacupuncture， with sparse and dense waves， once every other day. Both groups were treated for 90 days. Before treatment and after 30， 60， 90 and 120 days （follow-up）， patients of both groups were observed for House-Brackmann Facial Nerve Grading （HB） and modified Portmann score； facial nerve electromyography was performed before treatment and after 90 days of treatment to record the wave amplitude and latency of facial nerve motor conduction， and serum brain-derived nerve growth factor （BDNF）， nerve growth factor （NGF）， fibroblast growth factor （FGF2） levels were determined. The clinical effectiveness of both groups after 90 days of treatment was compared， and the adverse events occurred in the course of treatment in all patients were recorded. ResultsAt 30 days， 60 days， 90 days and follow-up visits， the HB grading of patients in both groups improved compared with that before treatment （P＜0.05）； the distribution of the number of patients with HB grading in the point ligation plus catgut embedment group was superior to that in the electroacupuncture group after 60 days and 90 days of treatment and at follow-up visits （P＜0.05）. The maximal amplitude of the facial nerve electromyography in both groups after 90 days of treatment was large， and the latency was shorter when compared with those before treatment （P＜0.05）， and the maximum wave amplitude of the point ligation plus catgut embedment group was higher than that of the electro-acupuncture group， and the latency period was shorter than that of the electro-acupuncture group （P＜0.05）. The modified Portmann scores of the both groups of patients after 30， 60 and 90 days of treatment and follow-up were higher than those before treatment， and the scores of the point ligation plus catgut embedment group were higher than those of the electroacupuncture group （P＜0.05）. Serum BDNF， NGF and FGF2 levels in both groups after 90 days of treatment were higher than before， and the point ligation plus catgut embedment group was significantly higher than the electroacupuncture group （P＜0.05）. The total clinical effective rate of the point ligation plus catgut embedment group （92.68%） was higher than that of the electroacupuncture group （81.01%， P＜0.05）. Adverse reactions occurred in both groups， mainly including local haematoma or subcutaneous bleeding， allergic reaction， severe pain， and needle fainting， all of which disappeared after symptomatic treatment. ConclusionThe point ligation therapy combined with catgut embedment in acupoint for patients with refractory facial paralysis are effective. The therapy improve the facial nerve function， and its mechanism of action may be related to increasing the level of serum neurotrophic factor and thus promoting facial nerve repairment.

Neovascular glaucoma is classified as a type of refractory glaucoma. Its pathological manifestation is the formation of neovascularization of iris and chamber angle, and then the formation of neovascularization membrane. The contraction and traction of neovascularization membrane make the iris and chamber angle adhesion close, which leads to the obstruction of aqueous humor outflow and the sharp increase of intraocular pressure. Excessive intraocular pressure not only causes severe headache and eye pain, but also damages the optic nerve and affects the patient's vision, which can lead to blindness. At present, there are many methods for the treatment of neovascular glaucoma, such as panretinal photocoagulation, anti-vascular endothelial growth factor, local or systemic administration of intraocular pressure lowering drugs and anti-glaucoma surgery. The aim is to reduce neovascularization, preserve visual function and improve symptoms as much as feasible. However, due to the complex pathogenesis and pathological changes of neovascular glaucoma, the treatment of neovascular glaucoma is more difficult than primary glaucoma, and the prognosis is worse. Understanding its pathogenesis and treatment methods can aid in selecting the most appropriate treatment strategy based on individual circumstances. Therefore, this review will summarize the pathogenesis and treatment of neovascular glaucoma.

Objective To investigate the effects of perineal massage combined with hip joint exercise on the outcome of delivery and mental resilience of primipara.Methods 90 pregnant women in the third trimester(after 36 weeks)who obtained the knowledge about perineal massage from midwife clinic were randomly divided into two groups with 45 cases each.The control group received regular antenatal examination and family self-exercise;the experimental group received perineal massage and hip joint training combined treatment.The delivery outcome,birth experience and maternal mental resilience of the two groups were compared.Results the number of vaginal delivery in the experimental group were higher than that in the control group(P<0.05);the second stage of labor was significantly shorter than that of the control group(P<0.05);the perineal integrity rate was higher than that of the control group(P<0.05);the scores of all dimensions in delivery experience questionnaire were higher than that of the control group(P<0.05);the scores of all dimensions in maternal mental resilience were higher than those of the control group(P<0.05)after intervention.Conclusion The perineal massage which conducted by midwives combined with hip movement can effectively improve the quality of delivery,relieve the negative emotions of pregnant women,improve the psychological elasticity level of pregnant women,and improve the delivery outcomes.

BACKGROUND:Postoperative delirium is one of the serious complications after total knee arthroplasty,usually occurring 1-5 days after surgery,with confusion and cognitive impairment as the main manifestations,which is not conducive to the recovery of joint function in elderly patients.At present,the risk factors affecting delirium after total knee arthroplasty in the elderly are not clear,and there is a lack of clinical prediction studies to directly present them for promotion and application. OBJECTIVE:To explore the risk factors of delirium after total knee arthroplasty in elderly patients and establish a prediction model of nomogram. METHODS:Medical record data of 116 elderly patients receiving total knee arthroplasty treated in Ganzhou Hospital of Traditional Chinese Medicine,Jiangxi University of Chinese Medicine from January 2019 to December 2021 were retrospectively analyzed,of which 29 elderly patients with delirium after total knee arthroplasty were selected as the observation group,and the remaining 87 elderly patients without delirium after total knee arthroplasty were selected as the control group.Preoperative general clinical data,laboratory examination results,and surgical data were compared between the two groups.Multivariate Logistic regression analysis was used to analyze risk factors for delirium after total knee arthroplasty in elderly patients.The receiver operating characteristic curve was used to analyze the independent risk factors and obtain the best cut-off value.The nomogram model was constructed by R software. RESULTS AND CONCLUSION:(1)There were significant differences in age,cerebrovascular accident history,preoperative hospital stay,preoperative albumin,hemoglobin,American Society of Anesthesiologists classification,operation time,anesthesia time,and intraoperative blood transfusion volume between the two groups(P<0.05).(2)Multivariate Logistic regression analysis showed that old age,long hospital stay before surgery,high American Society of Anesthesiologists classification grade,and long operation time were risk factors for postoperative delirium in elderly knee arthroplasty patients,while high albumin and high hemoglobin were protective factors for postoperative delirium in elderly knee arthroplasty patients.(3)The areas under the curve of age,preoperative hospital stay,albumin,hemoglobin,American Society of Anesthesiologists classification grade,and operation time were 0.784,0.706,0.853,0.762,0.617,and 0.542,respectively.The optimal cut-off values were 75 years,7 days,40 g/L,125 g/L,3 and 200 minutes,respectively.(4)After internal data for verification,the consistency index was 0.974.The actual curve of the model was in good agreement with the ideal curve.(5)These results indicate that this nomogram model based on old age,long hospital stay,high American Society of Anesthesiologists classification grade,low albumin,low hemoglobin,and long operation time has far-reaching clinical significance for early identification,early warning and diagnosis of delirium risk in elderly patients after total knee arthroplasty.

Objective To develop a method for rapid determination of the dissolution of cefixime capsules,to explore the consistency of the dissolution curves of the generic and reference preparations in different media,and to assess the reliability of the in vitro dissolution evaluation method according to the results of bioequivalence studies.Methods The dissolution test was performed by the paddle method at 50 r·min-1,using pH1.2 hydrochloric acid solution,pH6.8 phosphate buffer solution,pH7.5 phosphate buffer solution,and water as the dissolution media.And a high-performance liquid chromatography(HPLC)method with a core-shell column was established to determine the dissolution curves of the generic and reference preparations respectively.The bioequivalence of the generic and reference preparations was evaluated through the bioequivalence(BE)test.Results The similarity factors(f2)of the three batches of the generic and reference preparations in the four media were greater than 60.The fasting and postprandial pharmacokinetic parameters(Cmax,AUC0-t,AUC0-∞)of the generic and reference preparations in hu-mans were all in line with the bioequivalence standard.Conclusion The in vitro dissolution behavior of the generic and refer-ence preparations was consistent,and the two preparations were bioequivalent.The method is simple and quick,and it can be em-ployed to measure the dissolution of cefixime capsules,which can provide references for the consistency evaluation of cefixime capsules.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.