Objective To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assis-tance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury.Methods A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022.Among them,39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of(44.98±7.33)years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy in-cluding 24 males and 13 females with an average age of(44.37±10.82)years old.Among them,42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation(INFIX)or suprapubic support screws to fix the anterior pelvic ring.Postoperative follow-up time,operation time,complications of the two groups were compared.Results of Matta reduction criteria,Majed efficacy evaluation,the CT grading and the rate of secondary surgical revision were com-pared.Results The nailing time of(32.63±7.33)min in CT group was shorter than that of(52.95±10.64)min in C-arm group(t=-9.739,P＜0.05).The follow-up time between CT group(11.97±1.86)months and C-arm group(12.03±1.71)months were not statistically significant(P＞0.05).The postoperative complication rates between two groups were not statistically significant(x2=0.159,P＞0.05).Results of Matta reduction criteria(Z=2.79,P＜0.05),Majeed efficacy evaluation(Z=2.79,P＜0.05),CT grading(Z=2.83,P＜0.05)in CT group were better than those in C-arm group(P＜0.05);the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group(x2=5.641,P＜0.05).Conclusion Compared with traditional C-arm fluoroscopy,intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time,high accuracy and safety,and significant decrease in postoperative sec-ondary revision rate,and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Objective:To analyze the efficacy and safety of low-dose azacitidine in the treatment of senile myelodys-plastic syndromes(MDS).Methods:A total of 92 elderly MDS patients who were initially diagnosed in the Huaibei Miners General Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2018 to June 2022 were randomly divided into the observation group and the control group with 46 patients in each group.The observation group received a low dose of azacitidine 100 mg/d,dl-7,28 days as a course of treatment,6 courses in total,and the control group received a standard dose of azacitidine 75 mg(m2·d),d1-7,28 days as a course of treatment,a total of 6 courses of treatment.The clinical efficacy,overall survival(OS)and adverse reactions of the two groups of patients were observed.Results:There was no statistically significant difference in the clinical data between the two groups(P＞0.05).After treatment,the hemoglobin and platelet levels of the two groups of patients were significantly higher than before treatment in each group(P＜0.05).There was no statistically significant difference in leukocyte,hemoglobin and platelet levels between patients in the observation group and control group(P＞0.05).The number of cases with complete remission,partial remission,hematological remission,disease stabilization and disease progression in the observation group were 4,10,22,6 and 4,respectively,with a total effective rate of 78.26％.The numbers of cases with complete remission,partial remission,hematological remission,disease stabilization and disease progression in control group were 8,12,18,4 and 4,respectively,with a total effective rate of 82.61％.The total effective rate of patients in the observation group was slightly lower than that of the control group(x2=0.457,P=0.254).There was no significant difference between the two treatment schemes in the treatment of patients with blood transfusion dependence and patients with low risk,medium risk and high risk(P＞0.05).It takes 4 and 6 courses of treatment to achieve the best treatment response in the control group and observation group respectively.There was no significant difference in OS between the two groups(P＞0.05).In the observation group,there were 4,6 and 2 cases of infection,Ⅲ-Ⅳ degree myelosuppression and gastrointestinal reaction,respectively,with the incidence rate of adverse events being 26.09％.In the control group,there were 6,16 and 6 cases of infection,Ⅲ-Ⅳ degree myelosuppression and gastrointestinal reaction,respectively,with the adverse event rate was 60.87％.The incidence of adverse events in the control group was significantly higher than that in the observation group(x2=7.095,P=0.036).Conclusion:Elderly patients with MDS have poor tolerance to chemotherapy.Reducing azacitidine in the treatment of elderly MDS patients shows good efficacy and safety.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ²=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ²=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

In this report, a series of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead . The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound holds great promise as a potential drug candidate for the treatment of HIV-1 infection.

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Aged ; Animals ; Bone Density ; Diabetes Mellitus, Experimental/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/etiology* ; Rats ; Receptor, IGF Type 1/physiology* ; Signal Transduction ; Streptozocin ; beta Catenin/physiology*

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.
Consensus ; Diabetes Mellitus, Type 2/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Yin Deficiency

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier NCT00856544 and NCT00413699.
Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid ; drug therapy ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; adverse effects ; therapeutic use ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Pyrroles ; adverse effects ; therapeutic use ; Surveys and Questionnaires ; Young Adult

Objective To develop a simultaneous determination method of risperidone,paliperidone,olanzapine and quetiapine in human serum for therapeutic drug monitoring.Methods Clinical serum samples were prepared by protein precipitation and analytes were determined using HPLC-MS/MS.An Eclipse XDB C1s column (4.6 mm ×50 mm,1.8μm) was combined with mobile phase consisted of methanol,water and acetrile (37.5:12.5:50,plus 2.5 mmol · L-1 ammonium formate).The flow rate was 0.5 mL · min-1 The column temperature was 35 ℃ and the injection volume was 2 μL.MS detection was carried out using an electrospray ionization source operated in multiple reaction monitoring (MRM) mode.The ion transitions were m/z 427.3 → m/z 207.2(paliperidone),m/z 431.3--m/z 211.2 (paliperidone-D4),m/z 411→m/z 191 (risperidone),m/z 415.4→m/z195.2 (risperidone-D4),m/z 384.3→m/z 253.1 (quetiapine),m/z 392.3→m/z 258 (quetiapine-D8),m/z313→m/z 256 (olanzapine),m/z 316→m/z 256 (olanzapine-D3),respectively.Results The calibration curves of risperidone and paliperidone were y =0.67x +4.94 × 10-4 (R2 =0.999 4) and y =0.68x +0.14 × 10-2 (R2 =0.999 6),with the linear ranges of 1-100 ng · mL-1.The linear ranges were 2-200 ng · mL-1(calibration curve:y =1.33x-0.65 × 10-2,R2 =0.998 6) for olanzapine and 8-800 ng· mL-1 (calibration curve:y =1.80x-2.08 × 10-2,R2 =0.999 4) for quetiapine.The inter and intra-batch precisions of risperidone,paliperidone,olanzapine and quetiapine were all within 15 ％ in lower limit of quantitation (LLOQ),low,middle and high levels of quality control samples.The extraction efficiency was more than 90％ for four analytes.The concentration of analytes in quality control samples were less than ± 15 ％ bias compared with nominal concentration after storage at room temperature for 24 h,-70 ℃ for 34 d or after freeze-thaw for 3 cycles.Conclusion The validated method was simple,fast and sensitive for the simultaneous determination of risperidone,paliperidone,olanzapine and quetiapine in human serum.The method was applied to the therapeutic drug monitoring for patients administered with the above drugs.The stability of mixed quality control samples is reliable and can be used for therapeutic drug monitoring.

Insomnia and depression are common mental disorders and there exists bidirectionality between sleep symptoms and depressive symptoms.Cognitive behavioral therapy for insomnia (CBT-I) is recommanded first in patients with accute or chronic insomnia.Phannacotherapy treatment is recommended when CBT-I is insufficient or patients are comorbided with depression or other mental diseases.Pharmacotherapy treatment options include antidepressants,benzodiazepines,non-benzodiazepines,atypical antipsychotics as monotherapy or cotherapy.The aim of the present review was to discuss the selection and clinical application of sedative-hypnotic drugs in patients with comorbid depression and insomnia.