OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

AIM:To explore the feasibility of predicting orthokeratology lens ordering parameters(flat K, spherical power, lens diameter, and lens toricity)using the extreme gradient boosting(XGBoost)algorithm based on corneal topographic parameters and basic clinical examination indicators, and to provide references for intelligent clinical fitting.METHODS:Clinical data were retrospectively collected from myopic patients who underwent initial orthokeratology lens fitting and achieved successful fitting at Puyang Second People's Hospital between January 2019 and March 2024. Data from right and left eyes were treated as independent samples, and the dataset was partitioned at the patient level into training and test sets in a 7∶3 ratio. Input features included uncorrected visual acuity(UCVA), axial length(AL), horizontal visible iris diameter(HVID), flat K, steep K, horizontal eccentricity, and vertical eccentricity. The lens toricity prediction model additionally incorporated keratometric astigmatism(ΔK)and surface asymmetry index(SAI). The output labels were the final ordering parameters(flat K, spherical power, lens diameter, and lens toricity). Separate XGBoost regression models were constructed for each output parameter, with hyperparameters optimized independently through grid search combined with 5-fold cross-validation. Model performance was evaluated on the test set using the coefficient of determination(R2), mean absolute error(MAE), and root mean square error(RMSE). Feature importance analysis was also performed.RESULTS:Totally 400 patients(800 eyes)were included in the final analysis. The 400 patients comprised 208 male(52.0%)and 192 female(48.0%)patients, with a mean age of 10.1±2.3 y. After partitioning at the patient level, the training set comprised 280 patients(560 eyes; 146 males and 134 females; mean age 10.1±2.3 y), and the test set comprised 120 patients(240 eyes; 62 males and 58 females; mean age 10.0±2.2 y). No statistically significant differences in sex composition or age were found between the two sets(P>0.05). Toric lenses were used by 140 of the 280 patients(50.0%)in the training set and by 50 of the 120 patients(41.7%)in the test set(χ2=2.017, P=0.156). The flat K prediction model achieved an MAE of 0.34 D and an R2 of 0.84. The spherical power model attained an MAE of 0.43 D and an R2 of 0.70. The lens diameter model yielded an MAE of 0.12 mm and an R2 of 0.42. The lens toricity model(Tweedie regression, power=1.5)achieved an MAE of 0.44 D and an R2 of 0.38. The MAE for each parameter fell within the clinically acceptable tolerance limits(flat K≤0.50 D, spherical power ≤0.75 D, lens diameter ≤0.25 mm, lens toricity ≤0.75 D). Scatter plots and Bland-Altman analysis demonstrated strong agreement between predicted values and actual observations. Feature importance analysis revealed that flat K(0.70)and steep K(0.11)were the most influential predictors in the flat K prediction model.CONCLUSION: The XGBoost model based on routine clinical parameters provides predictions of flat K, spherical power, and lens diameter with MAEs within clinically acceptable ranges, and offers useful reference for cylindrical power prediction. This approach may serve as a useful adjunct to clinical lens fitting. Nevertheless, future prospective studies are warranted to validate its clinical utility in improving actual fitting success rates.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective To investigate the acquisition of the"standard for intubation and maintenance of nasointestinal tube in adult patients"of Chinese Nursing Association,and its influencing factors,so as to provide a basis for targeted training programs.Methods A multi-centered,cross-sectional study was performed in 31 provinces from September to November 2023,and nurses from different departments which use nasointestinal tubes like intensive care units,gastroenterology,neurology,geriatrics were included by a convenient sampling method.The tool was a self-designed questionnaire based on the group standard and the survey was conducted.Multiple linear regression analysis was used to explore the influencing factors of nurses'knowledge of nasointestinal tubes intubation and maintenance.Results 1 350 valid questionnaires were collected.Only 61.63％of the respondents knew about the publishing of the standard.The score of knowledge of tube intubation and maintenance was(61.09±13.56).The results of multiple linear regression analysis showed the influencing factors of the score of knowledge of intubation and maintenance were as follows:education level,professional title,job position,intubation experience within half a year,and corresponding achievements(P＜0.05).Conclusion The acqui-sition level of nurses for the standard calls for continuous promotion.Nursing managers should establish targeted training programs based on the related influencing factors,so as to advance the implementation of the group standard.

AIM To explore the clinical effects of Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes on patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment.METHODS One hundred and sixty patients were randomly assigned into control group(80 cases)for 4-week intervention of both warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules,and observation group(80 cases)for 4-week intervention of Heiguteng Zhuifeng Huoluo Capsules,warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules.The changes in clinical effects,TCM syndrome scores,WOMAC scores,Lequesne indices,pain mediators(PGE2,β-EP),growth factors(TGF-β1,IGF-1),bone metabolism indices(OPG,RANKL),TLR4/NF-κB signaling pathway and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC scores,Lequesne indices,PGE2,RANKLE,TLR4,NF-κB(P＜0.05),and increased β-EP,growth factors,OPG(P＜0.05),especially for the observation group(P＜0.05).No serious adverse events or reactions were observable in the two groups.CONCLUSION For the patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment,Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes can safely and effectively alleviate clinical symptoms,improve knee joint pain,and enhance joint functions,whose action mechanisms may contribute to the inhibition of TLR4/NF-κB signaling pathway expression and regulations of serum TGF-β1,IGF-1,OPG,RANKL levels.

Objective:To observe the clinical efficacy of laparoscopic non mesh vaginal sacral fixation(LSC)in the treatment of pelvic organ prolapse(POP)patients with mainly middle pelvic defects.Methods:55 cases of laparoscopic non mesh LSC patients with POP with mainly middle pelvic defects were selected from August 2019 to February 2023 at Liuzhou Hospital of Guangzhou Women and Children's Medical Center.The surgical condition of POP patients were observed.Patients were followed up after surgery,the position and recurrence of the anterior vaginal wall(Ba)point,posterior vaginal wall(Bp)point,and vaginal apex(C)point in POP patients before and after surgery were observed.The preoperative and postoperative pelvic floor dysfunction questionnaire scores of POP patients treated by laparoscopic non mesh LSC were compared.And the occurrence of short-term and long-term complications in POP patients after surgery were observed.Results:Among the 55 POP patients with laparoscopic non mesh LSC,11 underwent bilateral adnexectomy,3 underwent bilateral salpingectomy,55 underwent anterior vaginal wall repair,28 underwent posterior vaginal wall repair,2 underwent paravaginal repair,and 28 underwent perineal laceration repair.Additionally,2 underwent tension free mid urethral suspension via the pubic posterior vaginal wall,and 3 underwent mid urethral folding.The average duration of the surgery was(197.8±48.7)minutes,and the intraoperative blood loss was 50(30,50)mL.The postoperative indwelling time of the urinary catheter was 2.0(1,3)days,the postoperative residual urine volume was 6(0,11)mL,and the hospital stay was 10(8,12)days.Among the 55 POP patients,all surgeries were successful,with a success rate of 100％.The follow-up period ended in September 2024,with an average follow-up time of(42.14±11.37)months.2 cases were lost to follow-up,and 53 patients were successfully followed up,including 48 outpatient follow-up patients and 5 telephone follow-up patients.Among the 48 outpatient follow-up patients,1 case had a recurrence of the anterior vaginal wall,with a recurrence rate of 2.08％(1/48).The patient did not undergo anterior vaginal wall repair during surgery,and after surgery,the patient felt that there was a mass protruding from the vagina.However,the symptoms improved on their own after rest,and no further surgery was performed.The comparison of Ba points,C points,and Bp points before and after surgery in 48 outpatient follow-up patients showed statistically significant differences(P＜0.05).The comparison of preoperative and postoperative pelvic organ prolapse distress inventory(POPDI),Urogenital distress inventory(UDI),and Pelvic Floor Distress Inventory-short From-20(PFDI-20)scores among 53 POP patients showed statistically significant differences(P＜0.05),there was no statistically significant difference in preoperative and postoperative colorectal-anal distress inventory(CRADI)scores among the 53 POP patients(P＞0.05).There were a total of 11 cases of postoperative complications in 55 POP patients,including 1 case of enteritis,2 cases of urinary tract infections,1 case of bladder injury,1 case of lower back pain,pelvic pain,and difficulty defecation,and 5 cases of newly developed urinary incontinence.The incidence of complications was 20.00％(11/55).The long-term follow-up results of POP patients showed that 4 patients had no sexual activity after surgery,and 49 patients resumed sexual activity after surgery,among them,47 patients reported an improvement in their sexual experience compared to before surgery,accounting for 95.92％(47/49).Two patients were unable to have normal sexual activity due to painful intercourse,accounting for 4.08％(2/49).Conclusion:Laparoscopic non mesh LSC treatment for POP patients with mainly middle pelvic defects has a high success rate,few complications,good short-term and long-term follow-up effects,and can significantly improve pelvic floor dysfunction symptoms.

Objective To explore the differences in clinical characteristics of sudden sensorineural hearing loss(SSNHL)between patients with coronavirus disease 2019(COVID-19)and those without-COVID-19.Methods 31 SSNHL patients with COVID-19 who were hospitalized in a department during the COVID-19 epidemic period(from December 2022 to January 2023)were included as the study group,and 12 SSNHL patients without COVID-19 who received treatment during the non-COVID-19 epidemic period(from December 2021 to January 2022)were co-llected as the control group.Two groups of patients received standardized treatment,and their clinical characteristics and prognosis were compared.Clinical characteristics of SSNHL patients with COVID-19 during the COVID-19 epidemic period were analyzed.Results The time interval from patients developed COVID-19 to the onset of SSNHL in the study group was 3-30 days.The time interval from onset to consultation were 3(1,7)days and 5(4,6)days in the study group and the control group,respectively,with no significant difference(P＞0.05).The average age of patients in the study group was(44.16±13.54)years,which was higher than that of the control group(35.23±9.24)years,and the difference was statistically significant(P＜0.05).The hearing at damaged fre-quency of the study group improved by 6.5(0.5,24.5)dB after therapy,which was lower than that of the control group(36.0[27.0,38.0]dB),with statistically significant difference(P＜0.05).There was a negative correlation of the interval of consultation with the average improvement level of hearing at damaged frequency(r=-0.318,P=0.033).The longer the interval,the less the hearing improvement and the worse the therapeutic effect.Corre-lation analysis was further conducted on the time interval from development of COVID-19 to SSNHL onset and the time interval of consultation in patients in the study group,which showed no correlation(r=-0.337,P=0.059).There was no statistically significant difference in the types and degree of SSNHL between two groups of patients(both P＞0.05).After standardized treatment,the rate of ineffective patients in the study group was 56.25％,which was higher than that in the control group(15.38％),and the difference was statistically significant(P＜0.05).Conclusion After adjusting the COVID-19 prevention and control policies,there are more hospitalized COVID-19 patients with SSNHL,with a higher proportion in patients of older age,with poorer efficacy,and inef-fective treatment.The earlier the treatment for SSNHL patients,the better the effect can achieve.COVID-19 may be a potential inducement and/or etiological factor of SSNHL,and further research is needed.

This study aims to establish BHK-21 stable cell lines expressing APN from four species(human,pig,dog,and cat),the APN fragments were amplified from pEGFP-C1-APN plasmids of the four species stored in the laboratory to generate the recombinant plasmids pcDNA4.0-APN.Af-ter the recombinant plasmids were transfected into BHK-21 cells,the stable BHK-21 cell lines ex-pressing the APNs were selected by two rounds of limited dilution.The constructed BHK-21 cell lines were identified by indirect immunofluorescence assay(IFA),and their susceptibility to PD-CoV and TGEV was tested for these four cell lines.Virus infection experiments revealed that PD-CoV infected cells expressing human,pig,and dog APNs,while it did not infect cells expressing cat APN.Simultaneously,TGEV infected cells expressing pig,dog,and cat APNs,but did not infect cells expressing human APN.The results suggest that the risk of cross-species infection for different coronaviruses and the established cell line can be used effectively to evaluate the virus in-fection.The findings also revealed that PDCoV has the potential risk of cross-species infection of human and dog,and TGEV has the potential risk of cross-species infection of dog and cat.These results provide a basis for the prevention and control strategy of coronaviruses.

Objective:To explore the clinical features of Brucellar myelitis and diagnosis and treatment of secondary neuromyelitis optica spectrum disorder (NMOSD), and enhance the awareness of clinicians about this disease.Methods:A retrospective study was performed; 13 patients with Brucellar myelitis admitted to Department of Neurology, Inner Mongolia Autonomous Region People's Hospital from January 2020 to December 2024 were chosen. Clinical data were collected, and MRI images and serological changes during the infection period were observed. Serum and cerebrospinal fluid demyelinating antibody markers and cerebrospinal fluid oligoclonal bands (OCBs) in the suspected secondary inflammatory demyelinating diseases of the central nervous system patients were detected. All patients received standard antibiotic treatment and/or individualized immunotherapy depending on disease severity. The patients were followed up for 24 (12, 42) months. At the last follow-up, the neurological outcomes were evaluated using modified Rankin scale (mRS, scores of 0-2: good prognosis; scores of 3-6: poor prognosis).Results:(1) Among the 13 patients, 12 had motor disorder, 9 had bladder/bowel dysfunction, 7 had sensory abnormality, and 4 had other symptoms such as dizziness, behavioral changes, or unsteady gait. (2) MRI results showed that 8 patients had spinal cord abnormalities, including 2 with long-segment intramedullary high signal at T2-weighted image and 6 with short-segment local intramedullary high signal at T2-weighted image. Enhanced MRI was performed in 11 patients, with 2 showing lesion enhancement, 3 showing meningeal enhancement, and 6 showing no enhancement. (3) Four patients had elevated cerebrospinal fluid pressure (>180 mmH 2O); 9 patients had elevated cerebrospinal fluid protein level (>0.45 g/L). Brucella-specific DNA was detected in the cerebrospinal fluid of 6 patients. One patient was positive for OCB type II. One patient was positive for aquaporin 4 antibody (AQP4-IgG) in both serum and cerebrospinal fluid, and one patient was double positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG) and AQP4-IgG in serum. (4) All 13 patients received standard antibiotic treatment; 12 patients received immunotherapy. (5) Among the 4 patients with poor prognosis, 3 died and the remaining 9 had a good prognosis. The mRS score decreasing from 4 (3, 4) at admission to 2 (2, 3) at the last follow-up, showing an overall improvement in neurological function. (6) Among the 13 patients, 2 were diagnosed as having Brucellar myelitis secondary NMOSD. On the basis of antibiotic treatment, one AQP4-IgG positive patient was treated with high-dose glucocorticoids only and later died; one MOG-IgG and AQP4-IgG double positive patient was treated with intravenous immunoglobulin combined with high-dose glucocorticoids and sequential rituximab, with mRS score decreasing from 5 at admission to 2 at the last follow-up and good neurological function recovery. Conclusions:The clinical manifestations of Brucellar myelitis are diverse and overlap with the clinical features of NMOSD. For patients with suspected Brucellar myelitis secondary NMOSD, combination of immunosuppressant (such as rituximab) with antibiotics may be an effective individualized treatment.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.