OBJECTIVE To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects. METHODS UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway. CONCLUSION The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.

This study was designed to investigate the potential protective effect of isopimpinelline against para-chlorophenylalanine(PCPA)-induced pineal gland damage in rats.Forty male Sprague-Dawley(SD)rats were divided into four groups(n=10 each):a normal group,a model group,a melatonin-treated group(10 mg/kg),and an isopimpinelline-treated group(1.5 mg/kg).All groups,except for the normal,received intraperitoneal injection of PCPA(450 mg/kg)to induce pineal gland damage.Subsequent treatments were administered orally for 7 days.Sleep latency and duration were evaluated on the sixth day using the pentobarbital sodium sleep synergy test.After the treatment period,serum melatonin levels and pineal gland inflammation markers were assessed alongside oxidative and antioxidative parameters.Histological examinations of the pineal gland were conducted,and the expression of proteins related to the Nrf2 and NF-κB signaling pathways were quantified.Data showed that isopimpinelline alleviates the structural damage in the pineal gland of model rats,significantly elevated serum melatonin levels,and markedly improved sleep latency and duration(P＜0.05).Isopimpinelline activated the Nrf2 signaling pathway by inhibiting Keap1 expression,which facilitated the nuclear translocation of Nrf2 and upregulated the antioxidant proteins NQO1 and HO-1,thereby mitigating oxidative stress in the pineal gland(P＜0.05).Furthermore,isopimpinelline significantly reduced the levels of pro-inflammatory cytokines IL-2,TNF-α and IL-6.Isopimpinelline also suppressed the NF-κB signaling pathway,reducing the expression of NF-κB p65,IKKβ,and p-IKKβ proteins,as well as the nuclear translocation of NF-κB p65(P＜0.05),thereby providing anti-inflammatory benefits.In conclusion,isopimpinelline could protect pineal gland from damage by activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway.

Purpose To explore the effect of compressed sensing(CS)technique with different acceleration factors on the quality of cardiac magnetic resonance cine sequences and feasibility of clinical application.Materials and Methods From January to July 2021,40 healthy volunteers were prospectively recruited for cardiac magnetic resonance cine imaging in Hefei First People's Hospital.Four scan protocols of volunteers were designed:SENSE 2 and CS-cine sequences with acceleration factors of 3,4 and 8.The imaging slices include four chamber heart,short axis heart,left ventricular two chamber heart and three chamber heart.Subjective score of image quality,left ventricular cardiac function and 16-segment myocardial thickness of SENSE 2 and CS3,CS4 and CS8 were compared and analyzed.Results Taking SENSE 2 image as the standard score of 5,the scores of CS3 and CS4 were above 3,and the scores of CS8 were below 3.There was no significant difference between the scores of four chamber heart and short axis heart images of CS3 and SENSE 2 sequence(all P>0.05).There were statistically significant differences in the subjective scores of image quality between the left ventricular two chamber heart and three chamber heart groups of each sequence(all P<0.05).There was no statistically significant difference in left ventricular function(left ventricular ejection fraction,left ventricular end systolic volume,left ventricular end diastolic volume,left ventricular stroke volume,left ventricular end-diastolic mass)(F=0.027,0.182,0.057,0.140,0.545)and myocardial thickness(F=0.052-7.366)among the four imaging schemes(all P>0.05).Conclusion Cardiac cine based on compressed sensing technology have good application prospects.With the increase of acceleration factors,the scanning time gradually decreases,and the corresponding image quality will also decrease.When the acceleration factor is 4,that is,the scanning time of the conventional cine sequence is reduced by 50%,the left ventricular function and myocardial thickness can still be accurately measured,and the image quality basically meets the diagnostic requirements.

Objective:To analyze the dosimetric differences between gamma knife stereotactic body radiation therapy (SBRT) and linear accelerator-based SBRT for lung tumors by comparison to provide a theoretical basis for the selection of treatment strategies.Methods:Seven patients who underwent SBRT for lung tumors in the Cancer Center of Affiliated Zhongshan Hospital of Dalian University from January 2022 to May 2023 were enrolled. Plans of gamma knife SBRT (γ_SBRT) or linear accelerator-based SBRT plans (X_SBRT) were designed for the 13 lesions in the patients, with adjacent lesions in the same patient sharing one plan. As a result, 10 γ_SBRT plans and 10 X_SBRT plans were obtained. All lesions received 30-50 Gy of radiation in 5-10 fractions. Then, dosimetric parameters were analyzed and compared between γ_SBRT and X_SBRT plans, including the target coverage, gradient index (GI), conformity index (CI), maximum dose ( Dmax); mean dose ( Dmean), and minimum dose ( Dmin) of planning target volumes (PTVs); lung volumes receiving 20 Gy or more ( V20), 10 Gy or more ( V10), 5 Gy or more ( V5), 100% of the prescription dose ( V100%), and 50% of the prescription dose ( V50%); Dmean and the percentages of lung volume receiving doses of 20 Gy or more (Lung_ V20) and 5 Gy or more (Lung_ V5) of ipsilateral lung; Dmean and Lung_ V5 of contralateral lung; and Dmax values of the esophagus, spinal cord, and heart. Results:Compared to X_SBRT plans, γ_SBRT plans exhibited superior GI, V20, V10, V5, V50%, the Dmean, Lung_ V20, and Lung_ V5 of ipsilateral lung, the Dmean and Lung_ V5 of the contralateral lung, and the Dmax of esophageal and heart ( z = -2.81 to -1.99, P < 0.05), higher Dmax and Dmean of PTVs ( z = -2.80, -2.80, P < 0.05), and longer delivery time ( z=-2.70, P<0.05). Meanwhile, there was no significant difference in target coverage, CI, and Dmax of the spinal cord ( P > 0.05). Conclusions:Gamma knife SBRT plans can achieve sharper dose falloff outside target volumes than linear accelerator-based SBRT plans. Gamma knife radiosurgery is expected to reduce the radiation dose to low-dose areas around PTVs and normal lung tissue in SBRT for lung tumors. However, it significantly prolongs the delivery time.

Objective:To evaluate the value of ultrasonographic features and classification defined by the Chinese-Thyroid Imaging Reporting and Data System (C-TIRADS) in differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) .Methods:Data of 87 patients who underwent thyroid nodule-related surgery at Tianjin Medical University General Hospital from Jan. 2019 to Feb. 2023 and whose postoperative pathology confirmed FTC or FTA was divided into FTC group (26 cases) and FTA group (61 cases) were retrospectively analyzed. The differences of general data, pathological diagnosis, surgical methods, ultrasonographic features of thyroid nodules and C-TIRADS classification between the two groups were compared. Multivariate Logistic regression analysis was used to screen the independent predictors related to the occurrence of FTC, a regression model was established based on the independent predictors and a nomogram was drawn. Bootstrap method was used to verify the nomogram internally, and ROC curve and calibration curve were drawn to evaluate the diagnostic efficiency and predictive ability of the nomogram.Results:There were statistically significant differences between orientation, echo, composition, calcification, margin, halo and C-TIRADS classification between groups (all P<0.05) ; maximum diameter, echotexture, blood flow, general data, pathological diagnosis and surgical methods had no statistically significant differences between groups (all P>0.05) .Single-factor logistic regression analysis showed taller-than-wide, peripheral calcification, blurred/irregular edges or external invasion, C-TIRADS 4B/4C class were candidate variables for predicting the occurrence of FTC ( OR=10.909, 19.059, 19.259, 49.333, all P<0.05). Multivariate logistic regression analysis showed that peripheral calcification, blurry/irregular edges or extra-thyroid invasion, C-TIRADS 4B/4C class were independent predictors for the occurrence of FTC ( OR=33.731, 11.620, 22.794, all P<0.05) .The nomogram of FTC occurrence was constructed based on the above three independent predictors, and the AUC was 0.920 (95% CI=0.854-0.986), which showed that the nomogram had high diagnostic efficacy, and the optimal diagnostic threshold determined by the Youden index was 0.23 (corresponding to the total score of the nomogram is about 52 points), the sensitivity was 88.5%, and the specificity was 82.0%. The calibration curve drawn by internal verification was close to the reference line, suggesting that the nomogram had a high predictive ability. Conclusions:The nomogram prediction model for FTC occurrence based on the ultrasonographic features and classification defined by C-TIRADS has high diagnostic efficiency and predictive ability, and can help in the preoperative identification of FTC and FTA.

Constraint-based genome-scale metabolic network models (genome-scale metabolic models, GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric constraints, other constraints such as enzyme availability and thermodynamic feasibility may also limit the cellular phenotype solution space. Recently, extended GEM models considering either enzymatic or thermodynamic constraints have been developed to improve model prediction accuracy. This review summarizes the recent progresses on metabolic models with multiple constraints (MCGEMs). We presented the construction methods and various applications of MCGEMs including the simulation of gene knockout, prediction of biologically feasible pathways and identification of bottleneck steps. By integrating multiple constraints in a consistent modeling framework, MCGEMs can predict the metabolic bottlenecks and key controlling and modification targets for pathway optimization more precisely, and thus may provide more reliable design results to guide metabolic engineering of industrially important microorganisms.
Genome ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Models, Biological ; Thermodynamics

Objective:To evaluate efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:A retrospective study was conducted among patients with AD who showed poor response to topical agents and then received standardized injections of dupilumab for 16 weeks in Department of Dermatology, Peking University First Hospital from June 1, 2020 to September 1, 2021. Basic information on the patients was collected, so were the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) scores recorded before and at weeks 2, 4, 8, 12, and 16 during treatment. Adverse reactions were recorded during treatment. Wilcoxon rank sum test was used to compare the scores of all patients at the end of follow-up with those before treatment.Results:A total of 57 patients were enrolled in the study, and all completed 16-week injections and follow-up. At week 16, the patients′ IGA, EASI, NRS, DLQI, and POEM scores significantly decreased from 4.0 (4.0, 5.0), 30.0 (17.2, 36.0), 9.0 (7.0, 10.0), 15.0 (11.5, 20.5), and 19.0 (15.5, 23.0) points respectively at baseline to 1.0 (1.0, 1.0), 4.0 (1.6, 7.3), 1.0 (0.0, 1.0), 3.0 (1.0, 4.0), and 4.0 (2.0, 4.0) points respectively ( Z = 6.65, 6.57, 6.59, 6.57, and 6.57 respectively, all P < 0.001). All the 5 scale scores showed a continuous downward trend within 16 weeks after the start of dupilumab treatment. During the follow-up period, no serious adverse reaction was observed, and only two patients developed conjunctivitis. Conclusion:Dupilumab shows marked efficacy in the treatment of AD, with favorable safety.

Objective:To evaluate the efficacy and safety of baricitinib in the treatment of moderate-to-severe atopic dermatitis (AD) .Methods:From June 2020 to June 2021, patients with moderate-to-severe AD who were insensitive or intolerant to topical agents were enrolled from Department of Dermatology, Peking University First Hospital. Before treatment, the patients were evaluated by 4 scales, including the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), and Dermatology Life Quality Index (DLQI) ; meanwhile, photos of skin lesions were taken, routine blood test was performed, blood biochemical indices and total IgE levels were measured. After exclusion of contraindications, the patients were treated with oral baricitinib at a dose of 2 mg/d for 16 weeks. Regular follow-up was conducted at weeks 1, 2, 4, 8, 12, 16 and 20 after the start of treatment, clinical evaluation was carried out with the above 4 scales, and adverse events were recorded during the treatment.Results:A total of 24 patients were enrolled in the study, and all completed 16-week oral treatment and 20-week follow-up. All the 4 scale scores showed a continuous downward trend within 20 weeks after the start of treatment. At week 20, the patients′ IGA, EASI, NRS, and DLQI scores significantly decreased from 4.13 ± 0.61, 37.59 ± 14.86, 6.83 ± 2.26 and 18.67 ± 8.64 points respectively at baseline to 1.12 ± 0.49, 4.53 ± 3.78, 0.72 ± 0.58 and 1.39 ± 0.85 points respectively ( t = 22.70, 10.55, 10.69, 8.40, respectively, all P < 0.001). During the follow-up period, no serious adverse reactions were observed; 3 patients experienced gastric discomfort at the start of oral treatment, but the symptoms disappeared after the treatment continued; 3 developed acute allergic manifestations (1 case of allergic conjunctivitis, 2 cases of acute urticaria), which resolved rapidly after the use of antihistamines without recurrence. Conclusion:Baricitinib can provide a safer and more effective treatment option for patients with moderate-to-severe AD, especially those who are insensitive or intolerant to topical agents and need systemic treatments.

Objective:To investigate the effect of O-arm navigation assisted posterior pedicle screw reduction and internal fixation of atlantoaxial fractures.Methods:A retrospective case-control study was conducted to analyze 37 patients with atlantoaxial fractures admitted to Third Hospital of Hebei Medical University from January 2016 to June 2018, including 22 males and 15 females, aged from 29 to 68 years [(50.9±9.8)years]. The posterior pedicle screw reduction and internal fixation was performed under O-arm navigation system (navigation group, n=24), and using free-hand technique (free-hand group, n=13). The operation time and blood loss were compared between the two groups. The Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) were used to evaluate the clinical efficacy before operation, 7 days operation and at the last follow-up. The complications were detected. A total of 86 screws were placed in navigation group (Neo grade 0: 83 screws, grade 1: 2 screws, grade 2: 1 screw ), and 44 screws were inserted in free-hand group (Neo grade 0: 36 screws, grade 1: 5 screws, grade 2: 2 screws, grade 3: 1 screw)( P<0.05). Classification of screw positions proposed by Neo et al was used to evaluate the position relationship between the screw and the bone cortex and the incidence of screw penetration. Results:All patients were followed up 24-38 months [(27.7±4.0)months]. The operation time in navigation group was (189.8±35.4)minutes, significantly shorter than (221.5±48.6)minutes in free-hand group ( P<0.05). The bleeding volume in navigation group was 300.0 (250.0, 537.5)ml , significantly less than 500.0 (425.0, 625.0)ml in free-hand group ( P<0.05). Both groups showed significantly enhanced JOA and decreased NDI after operation and at last follow-up, compared with those before operation ( P<0.05). However, there was no significant difference in JOA and NDI between the two groups ( P>0.05). No severe complications such as neurovascular injury occurred during operation. The incidence of cortical penetration was 3% (3/86) in navigation group and 18% (8/44) in free-hand group ( P<0.05). Conclusions:In the process of posterior atlantoaxial pedicle screw placement, the application of O-arm navigation can significantly reduce the operation time and amount of bleeding, and enhance the accuracy of pedicle screw implantation.

Objective:The study retrospectively identified the correlative factors of low back pain after single-level oblique lateral interbody fusion (OLIF).Methods:Records of 93 patients (55 males and 38 females) who underwent OLIF (oblique lateral interbody fusion) surgery for lumbar degenerative diseases from May 2016 to September 2019 were analyzed retrospectively and patients' age was 55.73±9.48 years (range 32-78 years). There were 18 patients underwent L 3, 4 segment (19.35%), 73 patients underwent L 4, 5 segment (78.50%), and 2 patients underwent L 5S 1 segment (2.15%). There were 43 patients underwent OLIF stand alone and 50 patients underwent OLIF combined with lateral or posterior internal fixation. The follow-up time was 22.86±5.90 months (range 12-32 months). According to whether the visual analog scale (VAS)≥3 at the last follow-up visit, the patients were divided into low back pain group and no low back pain group. The demographic characteristics (age, gender, body mass index and comorbidities), basic surgical data (surgical segments, surgical methods, surgical time, intraoperative bleeding, endplate injury or not during operation), imaging data (lumbar lordosis, segmental lordosis, intervertebral height and cage subside) and lumbar function were recorded. The potential related factors were analyzed by univariate analysis, and the factors with P<0.05 were selected in the multivariate logistic regression model. Then the risk factors of low back pain after OLIF were determined by multivariate logistic regression analysis. Results:Nineteen patients with VAS score equal or greater than 3 were included in low back pain group, and the remaining 74 patients were included in no low back pain group. There was no significant difference in baseline data such as age, gender, BMI, follow-up time and comorbidities between two groups. There was no significant difference in VAS score between the two groups before operation ( t=0.818, P=0.414), but there was significant difference in VAS score at last follow-up visit ( t=6.958, P<0.001). The incidence rate of osteoporosis in low back pain group (63.16%) was significantly higher than that in no low back pain group (25.68%) ( t=9.558, P=0.002). There was no significant difference in vertebral height between the two groups ( t=1.008, P=0.316), however, the vertebral height was higher in no low back pain group ( t=2.537, P=0.316) at the last follow-up. The incidence of cage subsidencewas 8.11% in no low back pain group and 36.84% in low back pain group and there was significant difference between the two groups ( t=10.381, P=0.001). Multivariate logistic regression analysis showed that osteoporosis ( P=0.009), intraoperative bone endplate injury ( P=0.031), decreased intervertebral space height ( P=0.029) and cage subsidence ( P=0.016) were associated with low back pain after single-level OLIF. Conclusion:Low back pain is one of the common complications after OLIF. Osteoporosis, intraoperative bony endplate injury, decreased intervertebral space height and cage subsidence were closely related to postoperative low back pain. In order to reduce the incidence of postoperative low back pain and improve the clinical outcomes, attention should be paid to the protection of the bony endplate, rational use of internal fixation and active anti-osteoporosis treatment after operation.