The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Aim To study the relationship between white blood cell count and clinical classification in patients with coronary heart disease and its clinical significance.Methods A total of 301 patients diagnosed with coronary heart disease in the Second Affiliated Hospital of Harbin Medical University from January 2022 to December 2023 were se-lected as the research subjects,and divided into stable angina pectoris(SAP)group and acute coronary syndrome(ACS)group based on their clinical manifestations and results of electrocardiogram,the differences of general data,biochemical indexes and cardiovascular indexes between the two groups were compared.Spearman correlation analysis was used to an-alyze the relationship between white blood cell count,neutrophil count and cardiovascular related indicators,including tro-ponin Ⅰ,N-terminal pro-brain natriuretic peptide(NT-proBNP),ejection fraction,left ventricular end-diastolic diameter(LVEDD),left atrial diameter,Gensini score,etc.ROC curve was employed to determine the cut-off point for diagno-sing ACS and SAP classification of coronary heart disease based on white blood cell count,and dividing patients into a group with normal white blood cell level and a group with above normal white blood cell level based on this cut-off point,the differences between the two groups were compared.Results The ratio of hyperlipidaemia history,white blood cell count,neutrophil count,C-reactive protein,platelet count,total cholesterol(TC),low density lipoprotein cholesterol(LDLC),troponin 1,NT-proBNP and Gensini score in the ACS group were significantly higher than those in the SAP group(all P＜0.05),while the ratio of aspirin use,the ratio of statin use,and ejection fraction in the ACS group were low-er than those in the SAP group(all P＜0.05).Spearman correlation analysis results showed that white blood cell count was positively correlated with C-reactive protein(r=0.443,P＜0.001),troponin Ⅰ(r=0.333,P＜0.001),NT-proBNP(r=0.245,P＜0.001)and Gensini score(r=0.341,P＜0.001),but negatively correlated with LVEDD(r=-0.212,P＜0.001).Similarly,neutrophil count was positively correlated with C-reactive protein(r=0.430,P＜0.001),troponin Ⅰ(r=0.325,P＜0.001),NT-proBNP(r=0.292,P＜0.001)and Gensini score(r=0.353,P＜0.001),but negatively correlated with LVEDD(r=-0.175,P=0.002).The cut-off point of white blood cell count in the diagnosis of ACS was 9.35×109 L-1(sensitivity was 56.7％,specificity was 93.1％).The patients were divided into normal white blood cell level group(n=202)and above normal white blood cell level group(n=99).Hyperlipidemia,smoking history,TC,LDLC,C-reactive protein,troponin Ⅰ,NT-proBNP and Gensini scores in above normal white blood cell level group were significantly higher than those in the normal white blood cell level group(all P＜0.05),while LVEDD was lower than that in the normal white blood cell level group(all P＜0.05).Conclusion White blood cell count can easily identify the high-risk type of coronary heart disease,and the cut-off point for the diagnosis of ACS is 9.35×109 L-1.

Aim To study the relationship between white blood cell count and clinical classification in patients with coronary heart disease and its clinical significance.Methods A total of 301 patients diagnosed with coronary heart disease in the Second Affiliated Hospital of Harbin Medical University from January 2022 to December 2023 were se-lected as the research subjects,and divided into stable angina pectoris(SAP)group and acute coronary syndrome(ACS)group based on their clinical manifestations and results of electrocardiogram,the differences of general data,biochemical indexes and cardiovascular indexes between the two groups were compared.Spearman correlation analysis was used to an-alyze the relationship between white blood cell count,neutrophil count and cardiovascular related indicators,including tro-ponin Ⅰ,N-terminal pro-brain natriuretic peptide(NT-proBNP),ejection fraction,left ventricular end-diastolic diameter(LVEDD),left atrial diameter,Gensini score,etc.ROC curve was employed to determine the cut-off point for diagno-sing ACS and SAP classification of coronary heart disease based on white blood cell count,and dividing patients into a group with normal white blood cell level and a group with above normal white blood cell level based on this cut-off point,the differences between the two groups were compared.Results The ratio of hyperlipidaemia history,white blood cell count,neutrophil count,C-reactive protein,platelet count,total cholesterol(TC),low density lipoprotein cholesterol(LDLC),troponin 1,NT-proBNP and Gensini score in the ACS group were significantly higher than those in the SAP group(all P＜0.05),while the ratio of aspirin use,the ratio of statin use,and ejection fraction in the ACS group were low-er than those in the SAP group(all P＜0.05).Spearman correlation analysis results showed that white blood cell count was positively correlated with C-reactive protein(r=0.443,P＜0.001),troponin Ⅰ(r=0.333,P＜0.001),NT-proBNP(r=0.245,P＜0.001)and Gensini score(r=0.341,P＜0.001),but negatively correlated with LVEDD(r=-0.212,P＜0.001).Similarly,neutrophil count was positively correlated with C-reactive protein(r=0.430,P＜0.001),troponin Ⅰ(r=0.325,P＜0.001),NT-proBNP(r=0.292,P＜0.001)and Gensini score(r=0.353,P＜0.001),but negatively correlated with LVEDD(r=-0.175,P=0.002).The cut-off point of white blood cell count in the diagnosis of ACS was 9.35×109 L-1(sensitivity was 56.7％,specificity was 93.1％).The patients were divided into normal white blood cell level group(n=202)and above normal white blood cell level group(n=99).Hyperlipidemia,smoking history,TC,LDLC,C-reactive protein,troponin Ⅰ,NT-proBNP and Gensini scores in above normal white blood cell level group were significantly higher than those in the normal white blood cell level group(all P＜0.05),while LVEDD was lower than that in the normal white blood cell level group(all P＜0.05).Conclusion White blood cell count can easily identify the high-risk type of coronary heart disease,and the cut-off point for the diagnosis of ACS is 9.35×109 L-1.

OBJECTIVE: To investigate the clinical value of analgesia and sedation under bispectral index (BIS) monitoring combined with hydraulic coupled intracranial pressure (ICP) monitoring in severe craniocerebral injury (sTBI). METHODS: (1) A prospective self-controlled parallel control study was conducted. A total of 32 patients with sTBI after craniotomy admitted to the intensive care unit (ICU) of the First People's Hospital of Huzhou from December 2020 to July 2021 were selected as the research objects. ICP was monitored by Codman monitoring system and hydraulically coupled monitoring system, and the difference and correlation between them were compared. (2) A prospective randomized controlled study was conducted. A total of 108 sTBI patients admitted to the ICU of the First People's Hospital of Huzhou from August 2021 to August 2022 were selected patients were divided into 3 groups according to the random number table method. All patients were given routine treatment after brain surgery. On this basis, the ICP values of the patients in group A (35 cases) were monitored by Codman monitoring system, the ICP values of the patients in group B (40 cases) were monitored by hydraulic coupling monitoring system, and the ICP values of the patients in group C (33 cases) were monitored combined with hydraulic coupling monitoring system, and the analgesia and sedation were guided by BIS. The ICP after treatment, cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, complications and Glasgow outcome score (GOS) at 6 months after surgery were compared among the 3 groups. In addition, patients in group B and group C were further grouped according to the waveforms. If P₁ = P₂ wave or P₂ and P₃ wave were low, they were classified as compensatory group. If the round wave or P₂ > P₁ wave was defined as decompensated group, the GOS scores of the two groups at 6 months after operation were compared. RESULTS: (1) There was no significant difference in ICP values measured by Codman monitoring system and hydraulic coupling monitoring system in the same patient (mmHg: 11.94±1.76 vs. 11.88±1.90, t = 0.150, P = 0.882; 1 mmHg≈0.133 kPa). Blan-altman analysis showed that the 95% consistency limit (95%LoA) of ICP values measured by the two methods was -4.55 to 4.68 mmHg, and all points fell within 95%LoA, indicating that the two methods had a good correlation. (2) There were no significant differences in cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, and incidence of complications such as intracranial infection, intracranial rebleeding, traumatic hydrocephalus, cerebrospinal fluid leakage, and accidental extubation among the 3 groups of sTBI patients (P > 0.05 or P > 0.017). The ICP value of group C after treatment was significantly lower than that of group A and group B (mmHg: 20.94±2.37 vs. 25.86±3.15, 26.40±3.09, all P < 0.05), the incidence of pulmonary infection (9.1% vs. 45.7%, 42.5%), seizure (3.0% vs. 31.4%, 30.0%), reoperation (3.0% vs. 31.4%, 40.0%), and poor prognosis 6 months after operation (33.3% vs. 65.7%, 65.0%) were significantly lower than those in group A and group B (all P < 0.017). According to the hydraulic coupling waveform, GOS scores of 35 patients in the compensated group were significantly higher than those of 38 patients in the decompensated group 6 months after operation (4.03±1.18 vs. 2.39±1.50, t = 5.153, P < 0.001). CONCLUSIONS The hydraulic coupled intracranial pressure monitoring system has good accuracy and consistency in measuring ICP value, and it can better display ICP waveform changes than the traditional ICP monitoring method, and has better prediction value for prognosis evaluation, which can replace Codman monitoring to accurately guide clinical work. In addition, analgesia and sedation under BIS monitoring combined with hydraulic coupled ICP monitoring can effectively reduce ICP, reduce the incidence of complications, and improve the prognosis, which has high clinical application value.
Humans ; Intracranial Pressure ; Prospective Studies ; Monitoring, Physiologic/methods* ; Craniocerebral Trauma ; Analgesia ; Cerebrospinal Fluid Leak

Objective : To investigate the correlation between nocturnal sleep duration combined with snoring in the first trimester of pregnancyand small for gestational age(SGA) ，large for gestational age(LGA) ． Methods : Multi- variate Logistic regression model was used to analyze the association between nocturnal sleep duration ，snoring， their combined effects and SGA，LGA. Results : Compared to nocturnal sleep duration 7 to 9 h in the first trimester of pregnancy，sleep duration＜7 h was positively correlated with SGA in male newborn( OR = 4. 22，95% CI : 1. 69 - 10. 52) ; After stratified by snoring，the sleep duration of snoring women＜7 h was positively correlated with SGA ( OR = 5. 68，95% CI : 1. 02－31. 51) ，and the sleep duration of non-snoring women＜7 h was positively correlated with LGA ( OR = 2. 10，95% CI : 1. 16 －3. 81) ． Conclusion Sleep duration＜7 h in the first trimester of preg- nancy is a risk factor for SGA and LGA，and snoring may enhance the association between sleep duration＜7 h in the first trimester of pregnancy and SGA．Pregnant women should keep adequate nocturnal sleep duration to reduce the risk of abnormal neonatal weight.

Objective:To investigate the mechanism of oxidative stress injury and possible pathways in glutaryl CoA dehydrogenase deficient (GCDH -/-) rats with high lysine diet (Lys). Methods:Four-week-old rats were randomly divided into 6 groups: wild type+standard diet group (WT, n=6), GCDH -/-+standard diet group (GCDH -/-, n=11), WT+Lys group ( n=8), GCDH -/-+Lys group ( n=13), WT+Lys+vitamin (V) E group ( n=7), and GCDH -/-+Lys+VE group ( n=12); rats in the WT group and GCDH -/- group were given standard diet, and rats in the WT+Lys group, GCDH -/-+Lys group, WT+Lys+VE group and GCDH -/-+Lys+VE group were given high lysine diet (4.7% Lys); rats in the WT+Lys+VE and GCDH -/-+Lys+VE group were given VE (100 mg/[kg·d]) by intragastric administration once per d, and rats in other groups were given normal saline by intragastric administration once per d. The body mass and survival of rats in each group were observed. Twenty-eight d after intervention, rats were injected intraperitoneally with 10% chloral hydrate and anesthetized; their brains were severed to obtain hippocampal tissues; and pathomorphological changes were observed by HE staining; the content/activity of glutathione peroxidase (GPx), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in the hippocampus were detected by ELISA; the protein expressions of P38, c-Jun N-terminal kinase (JNK) and extra-celluar regulated protein kinase (ERK) in the hippocampus were detected by Western blotting. Results:(1) The survival ratio of rats in the GCDH -/-+Lys group was 9/13, and that in the GCDH -/-+Lys+VE group was 11/12. From the 7 th d of intervention, the body mass of rats in the GCDH -/-+Lys group and GCDH -/-+Lys+VE group was significantly lower than that in the WT group ( P<0.05). (2) As compared with that in the WT group, MDA content in hippocampal tissues of rats in the GCDH -/-+Lys+VE group and GCDH -/-+Lys+VE group was significantly increased ( P<0.05). As compared with WT group, GCDH -/-+Lys group had significantly decreased GPx activity, CAT activity and SOD activity, and statistically decreased GSH content ( P<0.05). As compared with those in the GCDH -/-+Lys+VE group, the GPx activity, CAT activity, SOD activity, and GSH content in the GCDH -/-+Lys+VE group were significantly increased ( P<0.05). (3) Western blotting showed that as compared with that in the WT group, the P38 protein expression in the hippocampus of rats in GCDH -/-+Lys group and GCDH -/-+Lys+VE group was significantly increased ( P<0.05); as compared with GCDH -/-+Lys+VE group, the P38 protein expression in the GCDH -/-+Lys+VE group was statistically decreased ( P<0.05). Conclusion:There is oxidative stress injury in the hippocampus of GCDH -/- rats with Lys, whose possible mechanism is to activate P38 and initiate MAPK signaling pathway; VE protects GCDH -/- hippocampal cells from oxidative stress by decreasing P38 expression.

We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

Objective:To investigate the effect of decompression of optic nerve canal for traumatic optic neuropathy (TON) via lateral supraorbital approach.Methods:A retrospective case series study was performed to analyze clinical data of 23 TON patients admitted to First People's Hospital of Huzhou from December 2013 to June 2019. There were 16 males and 7 females, aged 17-51 years [(34.3±2.2)years]. Degree of visual impairment included count fingers in 4 patients, hand motion in 4, light perception in 9 and loss of light perception in 6. Visual evoked potential examination (VEP) was performed in 15 patients before surgery. The amplitude of P100 completely disappeared in 5 patients, and the amplitude of P100 was lower than the lower limit of normal value and the latency prolonged in 10 patients. The time from injury to operation was 3 h-14 days [(3.3±0.6)days]. All patients underwent decompression of optic nerve canal via supralateral orbital approach, and dural repair was performed simultaneously in 11 patients with dural rupture. Intraoperative fractures and meningeal tears, duration of operation, blood loss, and hospitalization duration were recorded. Combined with the classical visual acuity improvement assessment method and the World Health Organization (WHO) low vision and blind grading standard, visual acuity was compared before operation, at 10 days and 3 months after operation. Glasgow Coma Scale (GCS) was used to evaluate patients' state of consciousness in the course of the disease. Glasgow Outcome Scale (GOS) was used to evaluate the prognosis. Incidence of complications was observed as well.Results:All patients were followed up for 12-16 weeks [(13.5±2.4)weeks]. Intraoperative microscopic exploration revealed that all patients had optic nerve canal fracture, 3 patients had frontal fracture with dural rupture, and 8 patients had ethmoid bone fragment with anterior skull base dural rupture. The duration of operation was 108.5-224.3 minutes [(151.8±30.2)minutes], including (32.5±8.4)minutes for craniotomy. The intraoperative blood loss was 90.5-165.3 ml [(121.3±15.5)ml]. The hospitalization was 14-26 days [(19.7±3.4)days]. The visual acuity of 13 patients (57%) improved and 5 patients (39%) relieved from blindness 10 days after operation, showing significant difference compared with the preoperation ( P<0.05). The visual acuity of 17 patients (74%) improved and 9 patients (39%) relieved from blindness at 3 months after operation. There was significant difference in visual acuity examined between 10 days and 3 months after operation ( P<0.05). Six patients were invalid, and 4 of them had no light perception before operation and the amplitude of VEP examination completely disappeared. All patients had GCS of 15 when left the hospital and GOS of 5 at 3 months after operation. One patient had cerebrospinal fluid rhinorrhea and healed after 7 days of supine position. No secondary hematoma, epilepsy or intracranial infection occurred during follow-up. Conclusion:Optic canal decompression via the lateral supraorbital approach can improve visual acuity in early stage and increase the rate of out of blindness, with low postoperative complications and satisfactory functional recovery, which is worthy of clinical application.

Objective To investigate the efficacy and safety of Nocardiarubra cell wall skeleton (N-CWS) bladder irrigation in prevention of recurrence after transurethral resection for the treatment of non-muscle invasive bladder cancer (NMIBC).Methods The clinical data of patients with NMIBC treated by N-CWS and epirubicin collected between October 2013 and November 2018 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.All patients underwent TURBT.Among the 118 NMIBC patients,the average age was (65.1 ± 1 1.9) years,and the sex ratio (male/female) was 1.9∶1 (77/41).Patients were divided into two group:N-CWS group (n =55) and epirubicin group (n =63) according to different instillation regimens.N-CWS was given as an instillation of 800 μg in 50 ml of saline and maintained in the bladder for 2 h in the N-CWS group.Epirubicin was given as an instillation of 50 mg in 50 ml of saline and maintained in the bladder for 1 h in the epirubicin group.In the N-CWS group,mean agewas (64.9 ± 12.1) years and 37 (67.3％) were male.Multiple tumors were present in 17 (69.1％) patients.Tumor size was ≤3 cm in 49(89.1％) and 7(12.7％) had a history of NMIBC.Stage was Ta and T1 in 36(65.5％) and 19(34.5％),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 38(69.1％),13(23.6％) and 4(7.3％),respectively.Low risk,intermediate risk and high risk were present in 14 patients(25.5％),16 (29.1％) and 25 (45.5％),respectively.In the epirubicin group,mean age was (65.3 ± 11.2) years and 40(63.5％)were male.Multiple tumors were present in 19(30.2％) patients.Tumor size was ≤3 cm in 56(88.9％) and 11 (17.5％) had a history of NMIBC.Stage was Ta and T1 in 37(58.7％) and 26 (41.3％),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 44(69.8％),12(19.0％)and 7(11.1％),respectively.Low risk,intermediate risk and high risk were present in 13 (20.6％),19 (30.2％) and 31 (49.2％),respectively.The tumor recurrence,progression and adverse reactions after Intravesical Instillation in both groups were followed up and recorded.No significant differences were found between the two groups.Results A total of 118 patients were followed up.Mean follow-up time was (33.7 ± 5.4) months.25.5％ (14/55) in the N-CWS group vs.42.8％ (27/63) in the epirubicin group had recurrence after 5 years (x2 =3.922,P =0.048).The five-year RFS was higher in the N-CWS group than in the epirubicin group (74.2％ vs.56.5％,P =0.044).No significant difference was found in the progression rate between the two groups(5.5％ vs.7.9％,P =0.867).The incidences of adverse events in the two groups were 16.4％ (9/55) and 19.0％ (12/63),respectively.The N-CWS group had significantly fewer cases with urinary frequency and dysuria than the epirubicin group.No significant differences were found in other side effects.Conclusions Intravesical instillation of N-CWS after NMIBC TURBT was found to be a promising procedure to prevent recurrence and prolong the recurrence-free survival with less side effects.