Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective:Based on data mining, the basic acupoint selection rules of allergic rhinitis were discussed, which provided a reference for the clinical treatment of allergic rhinitis.Methods:Computer search for literature on auriculo-sensitive rhinitis in VIP, China National Knowledge Infrastructure, Wanfang, China Biomedical Database, PubMed, Embase, Web of Science, the search period was from establishment of the database until August 29, 2023. The frequency, symptom type and distribution of ear point prescriptions were counted, and the association rules and cluster analysis of ear point prescriptions were carried out.Results:A total of 109 studies were included, and 127 prescriptions for ear points were extracted, involving 33 ear points. The association rules showed that the lungs, inner nose, adrenal glands and wind creek were the core ear points, and the cluster analysis formed six types of combinations: "spleen, kidney, lung, wind creek""subcortical, trachea, liver, throat, shenmen" "large intestine" "internal nose, adrenal gland" "endocrine" "sympathetic, external nose".Conclusions:Auricle therapy for allergic rhinitis mainly involves lungs, inner nose, adrenal glands and wind creeks, and dialectical acupoints are selected according to internal organs and symptoms, providing reference and reference for clinicians.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

Objective To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI.Methods The rat models of the sham surgery group,AMI group and hyperlipidemia+acute myocardial infarction (HAMI) group were established.Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats.Principal compo-nent analysis,partial least squares-discriminant analysis,and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites.The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites.Results A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened,respec-tively.Among them,22 metabolites were common in both rat models.These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways.Within the 95% confidence in-terval,the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetyl-spermidine,3-methylhistamine,and thymine were greater than 0.95.Conclusion N8-acetylspermidine,3-methylhistamine,and thymine can be used as potential biomarkers for AMI diagnosis,and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI.This study can provide reference for the mechanism and causes of AMI identification.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Eag1(ether-à-go-go-1,also known as Kv10.1,KC-NH1)is a member of the KCNH gene family of voltage-gated potassiumion(K+)channels,which is mainly expressed in the central nervous system as well as in a variety of malignancies and plays an important role in tumor development.The study of the distribution and mechanism of action of Eag1 is of great impor-tance to reveal its physiological function and its association with pathological mechanisms.This paper reviews the current re-search progress on the physiological and pathological properties of Eag1,the relationship between Eag1 and tumor development and the anti-tumor application of Eag1 modulators.

Objective:To investigate the real experience of patients returning to work after total hip and knee arthroplasty, in order to provide a reference for patients to return to work successfully.Methods:We searched for qualitative studies on the real experience of patients after total hip and knee arthroplasty in the returning to work process at home and abroad in the databases such as Cochrane Library, PubMed and Embase, etc, and the search period was from the establishment of the library to May 29, 2023, and the results were integrated by Meta-integration.Results:A total of 6 studies were included, 46 results were extracted, and 9 categories were formed and integrated into 4 themes, patients had different motivations for returning to work, there were many factors influencing patients′ return to work, and patients were eager to be helped in the process of returning to work, and learned from experience to improve their confidence in successfully returning to work.Conclusions:Patients with joint replacement have many obstacles and psychological burden in the process of regression, and hope to receive support from many aspects. Healthcare workers should pay attention to the needs of these populations, provide improved medical support, and actively promote the return of patients to work.

Objective:To explore the clinical characteristics of neonatal ureaplasma meningitis.Methods:A retrospective analysis was conducted on the clinical manifestations, diagnosis, treatment, and follow-up of a case of ureaplasma parvum (UP) meningitis in a neonate with persistent cerebrospinal fluid (CSF) abnormalities, admitted to the Neonatology Department of the Children's Hospital of Chongqing Medical University on September 2021. Literature was searched using the keywords "neonate", "ureaplasma", and "meningitis" in databases including CNKI, Wanfang Medical Database, Yiigle, VIP Database, SinoMed, and Chinese Medical Care Repository, as well as PubMed, Embase, and Web of Science, from their inception to December 2023. The clinical characteristics of the cases obtained were analyzed in conjunction with the present case. Descriptive statistical analysis and Chi-square test (or Fisher's exact test) were used for data analysis. Results:(1) Case report: The patient was a female neonate, born at 30 +2 gestational weeks, who experienced severe asphyxia at birth and was transferred to the neonatal intensive care unit of our hospital after resuscitation involving mechanical ventilation and chest compressions at an external hospital. On the 7th day of birth, the patient developed seizures, and CSF examination indicated meningitis. Blood and CSF cultures were negative, and empirical anti-infective treatment for one month showed no significant improvement. On the 39th day of birth, metagenomics next generation sequencing (mNGS) of the CSF indicated UP positivity, confirming UP meningitis. The patient received ten weeks of quinolone antibiotics. During hospitalization, a ventriculoperitoneal shunt was performed due to hydrocephalus, and the patient was discharged after improvement. At 2 years and 1 month of follow-up, the patient had cerebral palsy (hemiplegic type) and was undergoing rehabilitation therapy. (2) Literature review: A total of 31 articles were retrieved, encompassing 46 cases, plus the present case, making a total of 47 cases. Among these, 57% (27/47) were preterm infants, 54% (22/41) were low birth weight infants (some articles did not report this item, hence the denominator is less than 47), and 76% (28/37) were born via vaginal delivery. Cases who developed symptoms within the first week accounted for 71% (24/34), and 74% (26/35) had mothers with ureaplasma infection or high-risk factors during pregnancy. The main clinical manifestations included fever [63% (20/32)], seizures or apnea/respiratory distress [each 44% (14/32)]. CSF examination mainly showed significantly elevated white blood cells [287×10 6/L (69×10 6/L-1 176×10 6/L)], decreased glucose [0.79 mmol/L (0.10-1.17 mmol/L)], and elevated protein [3.01 g/L (1.80-8.14 g/L)], with negative general bacterial cultures. CSF mNGS [30% (14/47)], CSF polymerase chain reaction [17% (8/47)], and CSF culture [66% (31/47)] were the main methods for detecting ureaplasma. Treatment primarily involved macrolide antibiotics alone [46% (16/35)] or in combination with other antibiotics [29% (10/35)]. The duration of anti-ureaplasma treatment ranged from 2 to 10 weeks. Intracranial hemorrhage and hydrocephalus were the most common neurological complications [66% (25/38) and 61% (23/38), respectively]. Among the 47 cases, 31 were infected with ureaplasma urealyticum (UU) and 15 with UP (one case was not typed). There were no significant differences in epidemiology, clinical manifestations, neurological complications, and prognosis between UP and UU meningitis. Compared to UU meningitis, a higher proportion of UP meningitis cases were treated with macrolide antibiotics [13/15 vs. 52% (14/27), χ2=5.09, P=0.024]. Among the 43 reported cases of ureaplasma meningitis with outcomes, 44% (19/43) experienced developmental delays or death. The case fatality rate of UU meningitis was higher than that of UP meningitis [39% (11/28) vs. 0/14, Fisher's exact test, P=0.007]. Conclusions:Neonatal ureaplasma meningitis lacks specific clinical manifestations and has a variable prognosis. When empirical anti-infective treatment is ineffective in infants with purulent changes in CSF, intracranial ureaplasma infection should be considered. Macrolide antibiotics alone or in combination with other antibiotics can be the first-choice treatment for ureaplasma infection.