Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

ObjectiveTo introduce the Hr gene of spontaneously mutated SHJH^hr mice into BALB/cAShjh inbred mice with clear genetic background,and provide a basis for study on the molecular mechanism of Hr gene mutation-induced abnormal phenotype and the application of this model.Methods Using a backcross-intercross breeding method guided by phenotypic monitoring, mutant genes from SHJH^hr mice bred by spontaneous mutation were introduced into inbred BALB/cAShjh mice by homozygous mutation introgression, and the mice were bred into BALB/cA.Cg.SHJH^hr (abbreviated as C.Cg.SHJH^hr) mice after 10 generations. The genotypes of 90 single nucleotide polymorphism (SNP) detection sites were analyzed in C.Cg.SHJH^hr mice by multiplex PCR library construction followed by next generation sequencing. Then 14 biochemical locus marker genes were detected in C.Cg.SHJH^hr mice according to the method of GB/T 14927.1-2008. Finally, whole genome exon sequencing was utilized to detect the mutated genes in this mouse. ResultsFrom May 2018 to March 2022, a total of 10 generations of backcross-intercross were conducted to complete the construction of the C.Cg.SHJH^hr mouse line. Among the 90 SNPs loci detected, except for rs13484115 and rs13484116, all the other loci had the same genotype as the recipient mice BALB/cAShjh. The results of biochemical marker gene detection showed that all the 14 loci of the mouse were the same as those of the recipient mouse. Whole genome exon sequencing found that the mouse had 109 site mutations compared with the recipient mouse strain, including 71 synonymous mutations, 1 stopgain, 37 missense mutations, and 20 genes involved in protein sequence alterations (including the reported Hr gene). ConclusionC.Cg.SHJH^hr mice were created. Through exon sequencing and genetic analysis, three Hr mutated genes and associated mutated genes that mainly cause phenotypic variations were identified, which provides a basis for expanding the application of C.Cg.SHJH^hr mice in biomedical research.

Objective:To investigate the characters and emergency treatment strategy of upper urinary tract stone obstruction complicated with urosepsis.Methods:Clinical data of 28 cases of urosepsis, caused by upper urinary tract stone obstruction and arranged for emergency admission in our hospital during January 2018 to December 2019, were retrospectively analyzed. There were 6 males and 22 females. The median age was 54(32-93)years old. All patients had fever with the temperature ranged from 38.5 to 41.0 ℃. The median course of disease was 3 (ranging 1-14) days. The systolic blood pressure ranged from 76 to 138 mmHg at admission. Hypotension group was defined as the systolic blood pressure<90 mmHg after admission. Normotensive group was defined as the systolic blood pressure≥90 mmHg. There were 12 cases in hypotension group, including 3 males and 9 females. The median age was 57 (ranging 32-93) years old. The stones located at left side in 7 cases and right side in 5 cases. The stones located at the upper ureter in 5 cases, middle ureter in 2 cases, lower ureter in 4 cases and renal calculi in one case. The median length of the stone was 10 (ranging 6-20) mm. Six cases suffered with diabetes mellitus. One case suffered with neuron system disease. 3 cases have history of recent extracorporeal shock wave lithotripsy(ESWL). There were 16 cases in normotensive group, including 3 males and 13 females with the median age of 53 (ranging 33-76) years old. The stones located at left side in 5 cases, right side in 9 cases and bilateral in 2 cases. The stones located at the upper ureter in 10 cases, middle ureter in 4 cases, lower ureter in 2 cases. The length of the stone was 10 (ranging 8-14) mm. There were 3 cases with neurological diseases and 3 cases with recent ESWL history. There was significant difference between hypotension group and normotensive group in ration of diabetes mellitus ( P=0.024). Blood routine examination, C-reactive protein (CRP), procalcitonin(PCT), blood and urine bacterial culture were performed in both groups. The patients were treated with empiric antibiotics after the evaluation based on the sequential organ failure assessment (SOFA). Patients with hypotension were given blood volume expansion, and vasoactive drugs were added when the blood pressure was still low. After the blood pressure was stable, the collection system decompression was performed. The difference of infection indicators and therapeutic methods between the two groups was compared. Results:There was no significant difference in median WBC [16.34 (2.55-41.65) × 10 9/L vs. 13.97(6.23-26.65) × 10 9/L, P=0.577], median CRP [143.0(74.2-200.0) ng/ml vs.110.0 (22.7-200.0) ng/ml, P=0.771] between hypotension group and normotensive group. The difference of PCT [95.5 (26.5-200.0) ng / ml vs. 57.6 (1.0-200.0) ng / ml, P=0.040] and PLT [65.5(14.0-170.0)×10 9/L vs. 73.0(17.0-412.0)×10 9/L, P=0.030] between hypotension group and normotensive group was statistically significant. The median SOFA scores of hypotension group and normotensive group were significantly different [8.5(3.0-13.0) vs. 5.0(2.0-8.0), P=0.001]. Ureteral stent placement was performed in 23 cases, and nephrostomy was performed in 5 cases. There was no significant difference in surgical drainage between the two groups ( P=0.887). Eight patients in hypotension group were admitted to ICU. There was no significant difference in the duration of antibiotic use between hypotension group and normotensive group [8 (3-12) d vs. 5 (3-7) d, P=0.453]. Sepsis was cured in both groups after decompression, fluid resuscitation and antibiotic treatment. Conclusions:In severe cases of upper urinary tract stone obstruction complicated with urogenic sepsis, septic shock may occur. The condition is urgent, severe and dangerous. Patients with hypotension had higher PCT and SOFA scores, and lower PLT. It is very important to carry out the collection system decompression drainage in time, liquid resuscitation, early effective antibiotic use.

Objective:To analyze variant patterns and characteristics of focal physiological uptake (FPU) in the tongue on 18F-fluorodeoxyglucose (FDG) PET/CT imaging in patients without a history of oral tumor surgery and radiotherapy. Methods:A total of 6 233 consecutive patients who underwent routine whole-body PET/CT scan between January 2013 and December 2017 in the First Hospital of Shanxi Medical University were investigated retrospectively, and 324 patients with a history of oral surgery and radiotherapy were excluded, the remaining 5 909 patients (3 418 males, 2 491 females, age range: 2-95 (average: 58) years) were enrolled. A part of the patients underwent local PET/CT scan and CT scan with diagnostic dose, covering the oral cavity on mouth-opening position. The morphological characteristics of FPU patterns were analyzed, and the maximum standardized uptake value (SUV max) was measured. Results:Seventy-six FPUs in 76 patients (49 males, 27 females, age range: 40-83 (average 64) years) identified by routine whole-body PET/CT scan were confirmed by clinical examination from a specialist in stomatology or follow-up for more than 6 months. Forty-one of the 76 patients subsequently underwent local PET/CT scan and diagnostic CT scan on mouth-opening position. The incidence of FPU in the tongue was 1.29%(76/5 909). The FPU patterns could be classified into three types: type Ⅰ with FDG uptake involved only anterior part of the tongue body in the midline (near the tip of the tongue), which showed as a " dotted" shape( n=68; 1.15%, 68/5 909); type Ⅱ with FDG uptake involved mainly middle part of the genioglossus muscle, which showed as a " bar-shorted" shape ( n=5; 0.08%, 5/5 909); type Ⅲ with FDG uptake involved large part of the tongue body and the genioglossus, which showed as a " T" shape( n=3; 0.05%, 3/5 909). The SUV max in patients with type Ⅰ and type Ⅱ were 5.53(4.53, 7.30), 19.50(17.10, 22.74) respectively. The SUV max in 3 patients with type Ⅲ were 23.34, 27.50 and 35.14, respectively. Conclusion:In patients without a history of oral tumor surgery and radiotherapy, the FPU in the tongue has its specific pattern, and PET/CT scan on mouth-opening position helps to reveal the detailed features.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H2S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall–Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H2S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Coadministration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H2S levels. Conclusions Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H2S-BDNF-Nrf2 signaling pathway.

Objective To explore the effect of 3d digital reconstruction and printing technology on the teaching of complex orthopedics. Methods A total of 90 interns in the Second Affiliated Hospital of Inner Mongolia Medical University from September 2016 to September 2017 were selected as research subjects. According to the different teaching methods, they were divided into control group (n=45) and experimental group (n=45). The former received traditional teaching;the latter used three-dimensional digital reconstruction and printing technology to print out complex fracture models of patients, digitally reproduced fracture classification, developed scientific surgical plans through fracture models, and simulated surgical fixation methods. Examination was divided into clinical skills and written exam according to exam outline requirements; Self-cognitive ability score included professional interest, fracture understanding, etc. The satisfaction of the medical students in the experimental group was determined using self-made questionnaires. t test was used to compare data between groups. Results Experimental groups' scores for surgical skills (84.36 ±0.28) and theoretical knowledge (87.55 ±0.44) were higher than the control group, and the differences were statistically significant (P<0.05). The professional interest of the experimantal group was higher than that of the control group, and the difference was statistically significant (P<0.05). The students' classroom atmosphere was significantly better compared with the control group, and the difference was statistically significant (P<0.05). Conclusion Using 3 d digital reconstruction and printing technology to establish modes in complex orthopedics teaching process can effectively improve interns' surgical skills and theoretical knowledge, and promote student satisfaction.

Objective: To investigate direct and indirect economic burden, psychological impact, and quality of life in patients with psoriasis. Methods: Patients with psoriasis were recruited nationwide from "the psoriasis patient mutual assistance network" , a WeChat official account of "psoriasis patient mutual assistance platform" , and WeChat groups of psoriasis patients in different regions between July and September in 2018. An internet-based online questionnaire survey was carried out on these patients by using a self-designed questionnaire and Dermatology Life Quality Index (DLQI) scale. Comparison of enumeration data was carried out by using chi-square test, and comparison of measurement data by using Mann-Whitney U test. Results: A total of 497 valid questionnaires were collected, and 497 patients with psoriasis were enrolled into this survey, including 190 patients with mild to moderate psoriasis and 307 patients with severe psoriasis. These patients were from 8 geographic regions of China, and mainly in east China and north China. The total annual expenditure for psoriasis per patient accounted for 20% (8%, 50%) (M[P25, P75]) of the total annual income, the annual hospitalization rate was 21.3%, the annual sick leave or absence duration was 15.0 (1.0, 40.0) days, and the unemployment rate due to psoriasis was 37.0%. Of the 497 patients, 443 (89.1%) suffered from mental stress due to psoriasis, 169 (34.0%) had suicide intention, and 23 (4.6%) had ever attempted suicide. The DLQI score for all the patients was 14 (8, 19) , 307 (61.8%) patients reported a severe or extremely severe impact on the quality of life (DLQI > 10, severe psoriasis group) , and 190 (38.2%) patients reported a mild or moderate impact on the quality of life (0 ≤ DLQI ≤ 10, mild to moderate psoriasis group) . Compared with the mild to moderate psoriasis group, the severe psoriasis group showed a significantly higher ratio of total annual expenditure to total annual income (30% vs. 10.0%, P < 0.01) , hospitalization rate (26.4% vs. 13.2%, P < 0.01) , annual sick leave or absence duration (20.0 days vs. 5.5 days, P < 0.01) , unemployment rate (47.9% vs. 19.5%, P < 0.01) , proportion of patients with mental stress (99.0% vs. 73.2%, P < 0.01) , proportion of patients with suicide intention (46.3% vs. 14.2%, P < 0.01) and proportion of patients who had suicide behavior (6.8% vs. 1.1%, P < 0.01) . Conclusions Psoriasis imposes heavy economic and psychological burden on patients, and decreases their quality of life. Meanwhile, patients with severely or extremely severely affected quality of life have higher disease burden compared with those with mildly to moderately affected quality of life.