ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

Objective To evaluate the clinical screening value of the Epworth sleepiness scale(ESS)for patients with type 2 diabetes mellitus(T2DM)and obstructive sleep apnea hypopnea syndrome(OSAHS).Methods A total of 399 hospitalized T2DM patients were selected for portable monitoring(PM)and ESS assessment.Based on the presence or absence of OSAHS,the study was divided into a simple T2DM group(T2DM,n=143)and a group with comorbid OSAHS(OSAHS,n=256).According to the apnea-hypopnea index(AHI),the study participants were categorized into a normal group(AHI<5 times/h,n=143),a mild OSAHS group(AHI 5～15 times/h,n=147),a moderate OSAHS group(AHI>15～30 times/h,n=69),and a severe OSAHS group(AHI>30 times/h,n=40).Differences in ESS scores across various OSAHS severity groups were compared.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the screening value of ESS for OSAHS.Results Body mass index,proportion of obesity,proportion of central obesity,serum creatinine and fasting C-peptide were significantly higher the OSAHS group compared to the non-OSAHS group(P<0.05).Significant statistical differences in ESS scores were observed between the severe and mild OSAHS groups(P=0.006).When an ESS score of≥9 was used as the threshold for screening OSAHS,the concordance rate with PM diagnosis was 40.6%.ROC curve analysis revealed that the area under the curve(AUC)for ESS screening for OSAHS,moderate-to-severe OSAHS,and severe OSAHS,and their respective optimal thresholds(95%CI),were as follows 0.518(95%CI 0.459～0.577,P=0.545),0.571(95%CI 0.507～0.635,P=0.029)and 0.624(95%CI 0.531～0.718,P=0.010),with cutoffs of≥2 points,≥3 points,and≥4 points,respectively.Conclusions An increased ESS score in T2DM patients significantly indicates the likelihood of severe OSAHS.Using an ESS score of≥9 as a threshold to screen for OSAHS is ineffective,whereas an ESS score of≥3 for screening moderate-to-severe OSAHS and≥4 for severe OSAHS has some reference value.

SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Objective:To explore the optimal evidence for the nursing management of limb spasm in patients with spinal cord injury.Methods:Based on the "6S" evidence model, the databases including CNKI, Wanfang, PubMed and Cochrane Library, the guideline websites such as the National Guideline Clearinghouse, Guidelines International Network and Registered Nurses′ Association of Ontario, and the websites of professional associations such as the Royal College of Physicians, American Spinal Injury Association and Canadian Spine Association were systematically searched. Search period of each database was set from the year of inception until July 2022. Two investigators independently screened the literatures related to the management of limb spasm in patients with spinal cord injury, and conducted quality evaluation and evidence recommendation level evaluation.Results:Totally 17 literatures consisting of 6 guidelines, 3 expert consensuses, 5 systematic reviews, 2 evidence summaries, and 1 clinical decision were included. Moreover, 30 pieces of evidence were summarized from 3 aspects, including evaluation and identification, drug therapy (chemical denervation, and oral medication), rehabilitation training (hydrotherapy, electrical stimulation, magnetic stimulation, vibration therapy, heat and cold therapy, body position, and exercise therapy).Conclusion:Nursing staff can set up a multidisciplinary team according to the clinical environment and take into consideration of the characteristics of spinal cord injury patients to provide personalized interventions involving evaluation and identification, drug therapy, rehabilitation training, etc., so as to alleviate the degree of limb spasm.

Respiratory diseases are common， frequently-occurring clinical diseases. As the prevalence rate is increasing year by year， they have become a problem that seriously affects public health. The diseases are mainly located in the lung by traditional Chinese medicine （TCM） syndrome differentiation. Lung governs Qi and controls breathing and is also an organ for the storage of phlegm. Clinically， phlegm and Qi are often used for the treatment. Banxia Houputang （BHT）， originated from Synopsis of the Golden Chamber （《金匮要略》）， was used to treat plum-stone Ai （globus hystericus） at first. It is composed of Rhizoma Pinelliae， Cortex Magnoliae Offcinalis， Poria， Rhizoma Zingiberis Recens， and Folium Perillae， and treats diseases with the core pathogensis of mutual obstruction of phlegm and Qi. BHT has the effects of moving Qi， dissipating mass， descending adverse Qi， and resolving phlegm， which basically correspond to the pathological characteristics of the lungs. Clinical studies have confirmed that modified BHT can be used either alone or in combination with western medicine to treat chronic pharyngitis， asthma， chronic obstructive pulmonary disease， pneumonia， obstructive sleep apnea， upper airway cough syndrome and other respiratory diseases， with significant effects. It effectively improves the symptoms and signs of the diseases and reduces the recurrence rate. Basic research has shown that BHT plays anti-inflammatory， anti-oxidative stress， anti-apoptotic， autophagy-regulating， and iron overload-regulating roles by regulating the targets in multiple pathways. This paper， by combing the relevant literature in recent years， conducted a systematic review on BHT from the three aspects of syndrome analysis， clinical treatment research and mechanism research， with a view to providing theoretical basis and reference for the mechanism research of BHT in treating respiratory diseases and for expanding its clinical application.

Objective:To analyze the results of serum erythropoietin (EPO) in adults patients with Kaschin-Beck disease (KBD) in Qinghai Province.Methods:According to the "Diagnosis of Kaschin-Beck Disease" (WS/T 207-2010), by using clinical examination and X-ray, adults over 20 years old in KBD areas of Xinghai County and Guide County, Hainan Tibetan Autonomous Prefecture, Qinghai Province, were divided into KBD case group ( n = 109) and internal control group ( n = 95) in July 2019. At the same time, healthy people were selected as external control group ( n = 90) in Xunhua County. Then 2 ml fasting cubital venous blood was collected from the target population to separate serum. The serum EPO level was determined by enzyme-linked immunosorbent assay (ELISA). Results:There was no significant difference in age and sex ratio among the 3 groups ( F = 0.73, P = 0.484; χ 2 = 1.03, P = 0.611). There was significant difference in serum EPO levels among the 3 groups [KBD case, internal and external control groups: (30.74 ± 26.23), (19.73 ± 11.53) and (10.83 ± 4.48) U/L, F = 26.51, P < 0.001]. Multiple comparisons showed that there were statistically significant differences in serum EPO levels between KBD case group and the internal and external control groups ( P < 0.05), but there was no significant difference between the internal and external control groups ( P > 0.05). Conclusions:The serum EPO level in adult KBD patients in Qinghai Province is increased significantly.

Objective:To analyze clinicopathological characteristics of trauma-related melanoma and their relationship with the prognosis of patients.Methods:Clinical data were collected from 87 cases of trauma-related melanomas in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from 2009 to 2020, and their clinicopathological characteristics were retrospectively analyzed. Mann-Whitney test was used to analyze the difference in Breslow thickness of tumors between patients of different ages or genders; Spearman rank correlation analysis was used to analyze the correlation between the time from trauma to the notice of melanoma and Breslow thickness, Kaplan-Meier survival analysis and Log-Rank test were employed to analyze the relationship between clinicopathological characteristics of melanoma and the prognosis of patients; Cox regression model was used to analyze risk factors for survival duration of patients with trauma-related melanoma.Results:Among the 87 patients with trauma-related melanoma, 47 (54.02%) were males and 40 (45.98%) were females. Among them, melanoma occurred in 50 (57.47%) cases after sharp injuries, and in 37 (42.53%) after blunt injuries. In addition, 31 (35.63%) cases presented with primary lesions on the hands, and 48 (55.17%) on the feet. The Breslow thickness of the primary tumors was significantly higher in the group aged > 55 years than in the group aged ≤ 55 years ( U= 623.500, P= 0.010) , but there was no significant difference between patients of different genders ( P= 0.138) . The time from trauma to the notice of melanoma was negatively correlated with the Breslow thickness of tumors ( r=-0.203, P= 0.037) . The age of patients, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor significantly affect the survival duration of patients with trauma-related melanoma ( P= 0.011, 0.031, 0.002 and 0.031, respectively) ; the gender, type of trauma and ulceration of tumor mass did not significantly affect the survival duration of patients ( P= 0.618, 0.114 and 0.379, respectively) . Cox regression model analysis showed that the Ki67 proliferation index and Breslow thickness were independent risk factors affecting the prognosis of trauma-related melanoma (risk ratio [ RR] and 95% confidence interval [ CI] were 1.946 (1.234, 4.217) and 1.839 (1.014, 3.332) , P= 0.039 and 0.045, respectively) . Conclusion:The Breslow thickness of trauma-related melanoma is related to the age of patients and time from trauma to the notice of melanoma; the age, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor all affect the survival duration of patients with melanoma, and Ki67 proliferation index and Breslow thickness are independent risk factors affecting prognosis.

Objective:To understand the changes of serum interleukin (IL)-2 and IL-6 in adult patients with Kashin-Beck disease (KBD) in Qinghai Plateau, and to provide scientific basis for scientific prevention and treatment of plateau KBD.Methods:According to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), adult KBD patients and healthy people over 18 years old were selected as KBD group and control group, respectively, in KBD disease areas of Xinghai County and Guide County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. Fasting cubital venous blood was collected from the people of two groups, and the levels of serum IL-2 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 193 people were surveyed, including 114 people in KBD group and 79 people in control group. There was no significant difference in age and sex ratio between the two groups ( t = 0.204, χ 2 = 2.547, P > 0.05). The serum IL-2 and IL-6 levels of the KBD group were (572.21 ± 172.92), (42.35 ± 15.86) pg/ml, respectively; compared with the control group [(511.28 ± 173.22), (51.96 ± 17.18) pg/ml], the differences were statistically significant ( t = 2.404, 3.999, P < 0.05). Conclusion:The serum IL-2 level is increased and IL-6 level is decreased in adult KBD patients in Qinghai Plateau, both of which may be involved in the inflammatory reaction of adult KBD.

Objective:To explore surgical treatment strategies and prognosis of early-stage nail apparatus melanoma.Methods:A total of 115 patients with early-stage nail apparatus melanoma receiving surgical treatment were collected from Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from July 2011 to December 2019, and surgical treatment strategies and outcomes were analyzed retrospectively.Results:According to the modified ABCDEF criteria and clinical manifestations (such as deformation of the nail plate, ulcers, nodules) , 73 patients with early-stage nail apparatus melanoma received extended surgical resection based on the resection principles of melanoma in situ, 22 based on the resection principles of stage I and II melanoma, 20 based on the resection principles of stage I and II melanoma with invasion risks. During the follow-up period of 6 months to 9 years, there was no recurrence of the primary tumors in any patients; no abnormalities were observed by the ultrasound examination of lymph nodes in 101 patients; metastases occurred in 2 patients receiving finger amputation, 1 of whom died; 12 patients were lost to follow-up. Conclusion:To select extended surgical resection strategies for early-stage nail apparatus melanoma based on clinical manifestations, can ensure adequate treatment and preserve the normal function of the extremities to the greatest extent without recurrence of the primary tumors.