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.

In this paper， by referring to ancient and modern literature， the textual research of Kochiae Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， taste and efficacy， harvesting time， processing and compatibility taboo， so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation， it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic， and has been used as the official name throughout history. It is also known by other names such as Dimai， Dikui， and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia， which is consistent throughout history. In the Han dynasty， it was recorded that Kochiae Fructus was produced in Jingzhou（Hubei province）， while modern literature records its distribution throughout the country， so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn， and the quality is best when it is full， gray green in color， and no impurities. There are two processing methods for its origin：from the Southern and Northern dynasties to the Ming dynasty， it was dried in the shade， and after the founding of the People's Republic of China， it was dried in the sun. There are few records about the processing of Kochiae Fructus， and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar， and the leaves are taken in April and May， processing in the place of origin is shade drying， the processing methods include burning ash and frying frost， pounding juice and wine soaking. For internal use， it is mostly decocted or mashed， while for external use， it is mostly washed with decoction or taken in a soup bath. Throughout history， it has been recorded that Kochiae Fructus is bitter and cold， and is mainly used for treating bladder fever. After the founding of the People's Republic of China， most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia， it has been recorded that Kochiae Fructus has a pungent and bitter taste， and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness， dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history， it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times， it has been used to regulate the liver， spleen and large intestine meridians， with functions such as clearing heat and detoxifying， and diuresis. Based on the textual research， it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus， and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements， the raw products is taken into medicine.

In this paper， by referring to ancient and modern literature， the textual research of Cnidii Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， nature and flavour， efficacy， harvesting and processing， compatibility taboo and others， so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research， it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic， the materia medica of all dynasties was named Shechuangzi， and there are also aliases such as Shesu， Shemi， and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri， and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty， the origin of Cnidii Fructus was Zibo， Shandong province. During the Five dynasties， it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province， the Song dynasty added Shangqiu in Henan province， and it was considered that Yangzhou， Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China， the origin is clearly distributed throughout the country. For its quality evaluation， generally full grain， gray yellow color， strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month， and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products， mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past， there were also stir-frying with honey， stir-frying with salt and rice wine， immersing and steaming with rice wine and other methods. In recent times， it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter， Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm， acted on the kidney meridian， and had small toxicity. After the founding of the People's Republic of China， most of the literature classified it as a medicine to attack poison， kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness， destroying parasites and elieving itching， warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research， it is suggested that when developing the famous classical formulas containing Cnidii Fructus， the source shall be the dried ripe fruit of C. monnieri， and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas， the raw products can be taken into medicine.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

Objective To explore the magnetic resonance imaging(MRI)manifestations of acute cerebral infarction(ACI)and the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2),cystatin C(Cys C)and short-term prognosis.Methods A total of 110 ACI patients admitted to the department of neurology in our hospital from January 1,2022 to January 1,2023 were selected as the study objects.The clinical data and multimodal MRI were collected,and the serum Lp-PLA2 and Cys C levels of patients were detected.The patients were divided into the good prognosis group and the poor prognosis group according to the modified Rankin scale(mRS)score 90 days after onset.The predictive value of MRI manifestations and Lp-PLA2 and Cys C levels for short-term poor prognosis was analyzed.Results There were statistically significant differences in the time from onset to admission,National Institute of Health Stroke Scale(NIHSS)score on admission,hypertension or diabetes,coronary heart disease or atrial fibrillation of patients between the good prognosis group and the poor prognosis group(P<0.05).The proportions of patients with ischemic penumbra,HV positive,cortical-subcortical infarction,large perforating branch infarction,small perforating branch infarction,bilateral anterior circulation infarction,posterior circulation infarction,anterior-posterior circulation infarction,middle cerebral artery(MCA)stenosis or occlusion,both internal carotid artery(ICA)and MCA stenosis or occlusion,posterior cerebral artery(PCA)or vertebral artery(VA)stenosis or occlusion and hemorrhage transformation in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).The Lp-PLA2 and Cys C levels of patients in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).Small penetrating branch infarction,posterior circulation infarction,anterior-posterior circulation infarction,MCA stenosis or occlusion,both ICA and MCA stenosis or occlusion,hemorrhage transformation,serum Lp-PLA2 and Cys C had certain predictive value for patients with short-term poor prognosis(P<0.05).Conclusion MRI manifestations(ischemic penumbra,HV positivity,different types of cerebral infarction,and vascular stenosis)and serum Lp-PLA2 and Cys C levels can predict the short-term prognosis of ACI patients and provide important reference for the formulation of clinical treatment plans.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective:To explore the value of nuclear proliferation index (MIB-1) in the diagnosis and prognosis of adrenal cortical carcinoma (ACC).Methods:A retrospective analysis was conducted on the clinical data of ACC patients and patients with benign adrenal lesions admitted to Beijing Union Medical College Hospital from June 2018 to August 2022. There were 59 cases in the ACC group, 25 males and 34 females, with a male to female ratio of 1∶1.4. Age (46.1 ± 2.1) years old, including 4 cases under 20 years old, 7 cases between 21-30 years old, 11 cases between 31-40 years old, 14 cases between 41-50 years old, 13 cases between 51-60 years old, 8 cases between 61-70 years old, and 2 cases over 70 years old. Body mass index (24.3 ± 2.4) kg/m 2. Systolic blood pressure (149.3 ± 5.2) mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure (93.4±1.7) mmHg. There were 51 cases of typical Cushing's syndrome, 52 cases of hypertension, 44 cases of elevated blood sugar, 16 cases of hypokalemia, and 16 cases of menstrual abnormalities and acne caused by androgen secretion. Laboratory examination: Blood glucose (7.2 ± 0.3) mmol/L, glycated hemoglobin (8.6 ± 1.4)%, total cholesterol (5.7 ± 0.3) mmol/L, and triglycerides (2.0 ± 0.3) mmol/L. 24-hour urine free cortisol (234.4 ± 39.0)μg/24 h, with 46 cases showing an increase, and at 8am, corticotropin releasing hormone (9.5 ± 4.1) pg/ml, with 48 cases showing a decrease. Blood free cortisol (401.2 ± 17.1)μg/dl, with 42 cases of rhythm disappearance. 17 cases showed elevated aldosterone levels. Dehydroepiandrosterone sulfate (713 ± 159)μg/dl, of which 16 cases increased. Neuroenolase (21.2 ± 5.3) ng/ml, of which 27 cases were elevated. Insulin like growth factor-1 was (272.0 ± 42.1) ng/ml, with 26 cases showing an increase. 46 routine high-dose and low-dose dexamethasone inhibition tests were not suppressed. 39 cases of tumors were functional. 59 cases underwent preoperative abdominal and pelvic contrast-enhanced CT, MRI, and B-ultrasound examination, and 21 cases underwent PET/CT examination. The tumors were located in 32 cases on the left, 26 cases on the right, and 1 case on both sides. The maximum diameter of the tumor was (9.6 ± 1.7) cm, with 43 cases ≤10 cm and 16 cases >10 cm. There were 5 cases with lymph node metastasis, 16 cases with distant metastasis, and 11 cases with local invasion. There were 4 cases of tumor ENSAT clinical staging stage Ⅰ(T 1N 0M 0 stage), 27 cases of stage Ⅱ(T 2N 0M 0 stage), 23 cases of stage Ⅲ(T 1-2N 1M 0 stage, T 3N 0M 0 stage), and 5 cases of stage Ⅳ(T 1-4N 0-1M 1 stage, T 3N 1M 0 stage, T 4N 0-1M 0 stage). Six cases were accompanied by tumor thrombi in the central adrenal vein, renal vein, and inferior vena cava. There were 53 cases of benign adrenal tumors, including 26 males and 27 females. Age (44.3±3.2) years old, typical manifestations of Cushing's syndrome in 28 cases, 24-hour urine free cortisol (176.4±41.2) μg/24 h. 27 cases showed disappearance of free cortisol rhythm. Dehydroepiandrosterone sulfate is normal. 23 routine high-dose and low-dose dexamethasone inhibition tests were not inhibited. The maximum diameter of the tumor is (4.2 ± 2.3) cm. T 1N 0M 0 stage patients undergo robotic or laparoscopic radical adrenalectomy, with the resection range including the surrounding lymphoid tissue of the tumor; Patients with stage ≥T 2 underwent open radical adrenalectomy and lymph node dissection. Six cases underwent radical adrenalectomy combined with nephrectomy due to tumor invasion of the kidneys with unclear boundaries. 11 cases of local implant metastasis underwent stereotactic radiotherapy. Nine patients with liver metastasis underwent Interventional Embolization treatment. Three cases with isolated lung metastases underwent surgical resection. Four cases of multiple lung metastases were treated with radiotherapy combined with mitotane. According to the postoperative pathological examination results, record the pathological Weiss score and MIB-1. Analyze the correlation between MIB-1 and clinical pathological indicators and prognosis of patients. Results:There were 59 cases in the ACC group, 35 cases of R0 resection, 19 cases of R1 resection and 5 cases of R2 resection.The postoperative pathological examination showed an average weight of approximately (371±52)g, with 42 cases having a tumor mass ≤ 300 g and 17 cases having a tumor mass>300 g. The positive rate of MIB-1 in the control group was 1% to 5%, while the positive rate of MIB-1 in the ACC group was greater than 5%, the difference between the two groups was statistically significant ( P<0.01). 53 patients diagnosed with capsule invasion, capsule rupture, intravascular tumor thrombus, and MIB-1>10% through postoperative pathological examination were treated with tumor bed radiotherapy and mitotan medication, followed by second-line combination immunotherapy and EDP chemotherapy. The 5-year survival rates of ACC patients with different tumor stages were 65% in stage Ⅰ, 58% in stage Ⅱ, 38% in stage Ⅲ, and less than 5% in stage Ⅳ. The total survival time of the two subgroups with low and high staging was 3.6 years and 1.1 years respectively ( P=0.003), while the disease-free survival time of the two groups was 25 months and 11 months, respectively ( P=0.011). R0 resection has a better prognosis than R1 and R2 resection, and its five-year survival rate is higher ( P=0.03). The 5-year survival rates of R0, R1, and R2 groups were 61%, 31%, and 17%, respectively( P=0.030).Survival analysis showed that adrenal cortical cancer patients with MIB-1 greater than 10% had a worse prognosis, with 5-year OS of 17% and 32% for both groups, respectively ( P=0.021). The Weiss score of the ACC group was (7±2). There were 21 cases in the Weiss score 3-5 group and 38 cases in the 6-9 group, the 5-year survival rates of the two groups were 62% and 19%, respectively ( P=0.017). Conclusions:MIB-1 can serve as an auxiliary diagnostic and prognostic indicator, and high expression of MIB-1 can contribute to the early diagnosis and determination of treatment strategies for ACC.

Objective To explore the characteristic categories of presenteeism among ICU nurses and analyse the influencing factor.Methods A convenience sampling method was adopted to select 391 ICU nurses as the study subjects from four Grade IIIA hospitals in Zhejiang Province in May 2023.A general information questionnaire,the Stanford presenteeism scale-6,and Maslach burnout inventor were used in the survey.R language was used for latent profile analysis,and univariate analysis and multinomial logistic regression analysis were employed to explore the influencing factors of the latent profiles.Results A total of 391 ICU nurses completed the survey,with the score of presenteeism at 16.10±4.64,which was at medium level.The score of presenteeism was further divided into four latent classes:low work limitation-low work energy type accounted for 13.04%,high work limitation-moderate work energy type accounted for 24.55%,low work limitation-high work energy type accounted for 4.86%,moderate work limitation-moderate work energy type accounted for 57.55%.The influencing factors include average monthly income,the score of emotional exhaustion and personal fulfillment dimensions in job burnout(all P<0.05).Conclusion The incidence of presenteeism among the ICU nurses has distinctive classification characteristics.Based on the identified influencing factors,nursing managers should provide individualised interventions to the ICU nurses with different latent profiles of characteristic categories to reduce the presenteeism among the nurses and thereby to improve the quality of nursing services.