Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Objective To observe the clinical effect of Jiu-Wei-Yong-An granule combined with cetirizine in the treatment of damp-heat accumulation syndrome of eczema. Methods 108 eczema patients with syndrome of damp-heat accumulated in the skin, treated in the Department of Traditional Chinese Surgery in the First Affiliated Hospital of Naval Medical University from December 2021 to March 2023, were selected. They were randomly divided into an observation group and a control group, 54 cases in each. Both groups took cetirizine tablets orally for basic treatment. The observation group was given Jiu-Wei-Yong-An granules, and the control group was given placebos of the same. The clinical efficacy before and after treatment in the two groups was observed and compared, including TCM syndrome scores, eczema area and severity index （EASI）, visual analogue scale （VAS）, and adverse reactions. Results After treatment, the total effective rate of the observation group （88.9%） was higher than that of the control group （77.8%）, and the difference was statistically significant （P<0.05）. After treatment, the TCM syndrome score, EASI and VAS in the observation group were significantly lower than those in the control group （P<0.05）, and the difference was statistically significant. There was no significant difference in the total rate of adverse reactions between the two groups （P>0.05）. Conclusion The combination of Jiu-Wei-Yong-An granules and cetirizine tablets in the treatment of damp-heat eczema showed significantly better clinical outcomes in the observation group compared to the control. It effectively improved patient conditions, reduced skin lesion areas, and alleviated itching, with both safety and efficacy that merit clinical promotion.

Objective To evaluate the clinical efficacy of Traditional Chinese Medicine （TCM）external treatment methods in alleviating skin pruritus caused by eczema through a Meta-analysis. Methods Randomized clinical trials investigating the use of TCM external treatment methods for skin pruritus caused by eczema were searched in databases including China National Knowledge Infrastructure （CNKI）, VIP, Wanfang, Sinomed, PubMed, Embase, LILACS, and Cochrane, up to December 2024. Two reviewers independently screened and entered the statistical data, conducted bias risk assessment by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0, and performed Meta-analysis using RevMan 5.4.1. Results Ultimately, 14 studies involving 1 788 patients were included. Compared to the control group, TCM external treatment methods （treatment group）showed better improvement in pruritus scores （Z=11.88, P<0.000 01）, better improvement in Eczema Area and Severity Index （EASI） scores （Z=23.15, P<0.000 01）, higher overall clinical efficacy rate （Z=6.21, P<0.000 01）, better improvement in TCM symptoms （Z=5.49, P<0.000 01）, and lower clinical recurrence rate （Z=2.88, P=0.004）. Three of the included studies mentioned adverse reactions, with the treatment group showing lower adverse reactions than the control group. Conclusion The external treatment of TCM was more effective in treating skin pruritus caused by eczema compared to the control group. Given the biases and heterogeneity in the included literature, this conclusion needs to be further substantiated by more large-scale, multi-center, randomized, controlled, and double-blind studies.

Objective To prepare Xuanyang Jiedu cream and to study its pharmacodynamics.Methods The herbal decoction process of Xuanyang Jiedu cream was optimized by orthogonal design method.The prescription of the cream preparation was screened according to the external properties,malleability and stability of cream.Forty normal guinea pig were randomly divided into four groups(10 in each group):blank group,model group,ketoconazole cream group,and Xuanyang Jiedu cream group.The guinea pig model of tinea corporis was established to investigate the efficacy of Xuanyang Jiedu cream in the treatment of superficial fungal disease.Results The optimal extraction conditions were 3 extractions,water added for 20 times,and 1.5 h of extraction time.The number of extractions and the amount of water significantly affected on the extraction process of the liquid extract.The optimized Xuanyang Jiedu cream looked smooth and creamy,with moderate viscosity and good stabilities of centrifuge,cold and heat resistance.After 14 d treatment,there were still obvious erythema,scales and papules on the lesions in the model group.The scores of erythema,scales and papules in the Xuanyang Jiedu cream group and the ketoconazole cream group were lower than those in the model group(P<0.05).Conclusion Xuanyang Jiedu cream has antifungal activity and may be a new treatment for skin superficial mycosis.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Drug loading is an important index to evaluate the quality of solid preparation of traditional Chinese medicine. Drug loading is restricted by drug characteristics, dosage form, process, and drug delivery in vivo, which affects the preparation process, therapeutic effect, and drug release rate. By consulting domestic and foreign literature, this paper put forward the significance of increasing the drug loading: improving the compliance of patients, reducing the production cost, reducing the risk of the excipients. In this review, the possible approaches to increase drug loading, such as the selection of high-efficiency excipients, suitable drug preparation techniques, and modification of the physical properties of drugs are summarized. It will provide theoretical basis through this review for the development of high drug loading and high-quality formulations.

Objective To investigate the clinical efficacy of semi-open cancellous bone grafting for infected bone defect combined with soft tissue defect of lower limb.Methods A retrospective case control study was conducted to analyze the clinical data of 26 patients with infected bone defect combined with soft tissue defect of lower limb admitted to the Third Hospital of Hebei Medical University from March 2010 to August 2017.There were 16 males and 10 females,aged 16-65 years [(39.6 ± 12.8)years].The bone defect area before bone grafting was 1.4-6.0 cm [(3.3 ± 1.2) cm].The surface soft tissue defect of bone graft granules was 2.3 cm × 1.1 cm-8.5 cm × 5.0 cm after bone grafting.If the defect was segmental defect of more than 6 cm,the defect was firstly reduced by bone transport.When the defect was near the docking point,the bone defect was repaired by open bone grafting.If the defect was located at the metaphyseal end of the calcaneus or tibia,stage Ⅰ or stage Ⅱ open bone grafting was performed after debridement.After bone grafting,antibiotic-containing cement sheets were used to cover the wound in 14 patients (semi-open group),and vacuum sealing drainage (VSD) devices were used to cover the wound in 12 patients (VSD group).The time of granulation tissue covering bone graft granules,wound healing time,bone defect healing time,material cost and complications (wound infection and necrosis of bone graft granules) were compared between the two groups.The limb function was evaluated according to Paley score.Results All patients were followed up for 12-40 months [(19.3 ±7.2) months].In the semi-open group and VSD group,the time of granulation tissue coverage was 22.2 days (15.0-44.0) days and 20.2 days (15.0-44.0) days (P ＞ 0.05);wound healing time was 3.1 months (1.5-5.5) months and 3.1 months (1.5-6.5) months (P ＞ 0.05);bone defect healing time was (5.5 ± 2.2) months and (5.9 ± 2.4) months (P ＞ 0.05);the cost of covering wound materials was (2 056.1 ± 23.4) yuan and (5 555.3 ± 1 105.5) yuan respectively (P ＜ 0.05).No wound infection occurred in either group.Two patients in the semi-open group and one patient in the VSD group had bone graft granules surface necrosis (P ＞0.05).According to Paley's functional score,the results were excellent in 12 patients and good in two in the semiopen group,compared with excellent in 11 and good in one in the VSD group (P ＞ 0.05).Conclusion For infected bone defect combined with soft tissue defect of lower limb,semi-open bone grafting can simplify the nursing of wound,prevent wound infection,promote wound healing and fracture healing.It has similar therapeutic effect with VSD,but its treatment cost is significantly reduced.

Objective: To investigate the regulation of AMPK-mTOR signal transduction pathway in paraquat-induced autophagy of pheochromocytoma cells (PC12) . Methods: The PC12 cell were treated with terminal concentrations of 0, 25, 50, 100, 200, 300 and 400 μmol/L PQ for 24 hours, and the cells were induced by 300 μmol/L PQ for different time (6, 12, 24, 48 h) . MTT was used to detect the relative survival rate of cells, and the dose/time-effect relationship was determined respectively. The cells were treated with PQ at concentrations of 0, 100, 200 and 300 μmol/L PQ for 24 hours, the lactate dehydrogenase (LDH) activity in the culture supernatant was detected by spectrophotometry. The expression and distribution of autophagic lysosomes were observed by MDC staining. The intracellular reactive oxygen species (ROS) was detected by dichlorofluorescein diacetate (DCFH-DA) . The expression of microtubule-related protein 1 light chain 3 (LC3) was measured by immunofluorescence. The protein level of LC3Ⅱ, p62, Beclin1 and p-AMPK, p-mTOR were detected by Western blot. Results: Compared with the control group, the cell survival rate of the 100, 200, 300, 400 μmol/L PQ group decreased significantly, and showed a dose-dependent pattern (P<0.05) . The survival rate of cells treated with 300 μmol/L PQ decreased significantly with the prolongation of exposure time (12, 24, 48 h) (P<0.05) . Compared with the control group, the activity of LDH in 100, 200, 300 μmol/L PQ-treated group were significantly higher while The fluorescence intensity of ROS was significantly increased (P<0.05) . MDC staining showed the density of autophagic lysosomes and fluorescence intensity in PQ-treated group significantly decreased (P<0.05) . Immunofluorescence results showed the LC3 fluorescence intensity of PQ-treated group decreased which was consistent with MDC staining results. Western blot showed that compared with the control group, the expression levels of autophagy related proteins LC3Ⅱand Beclin1 in PQ-treated group were significantly lower, while the expression level of p62 protein was higher (P<0.05) . p-AMPK protein level decreased and p-mTOR protein expression increased in 200 and 300μmol/L PQ-treatd groups, with statistically significant difference (P<0.05) . Conclusion AMPK-mTOR signaling pathway played a regulatory role in PQ-induced decreased autophagy of PC12 cell.

Objective To explore the clinical efficacy of rectangle advancement flaps used in the reconstruction of skin defects around the Achilles tendon in children.Methods From May 2014 to June 2015,7 children with skin defects around the Achilles tendon were admitted to our trauma center.The areas of skin defect ranged from 3.4 cm × 2.7 cm to 5.5 cm × 4.0 cm.The integrity of Achilles tendon was preserved in 6 cases but the tendon insertion was partly disrupted in one case.The skin defects were reconstructed with self-designed rectangle advancement flaps after debridement.In the one case with the Achilles tendon partly disrupted,the contaminated tendon ends were excised before wound closure.The injured ankles were immobilized in plantar flexion with one 1.5 mm K-wire and plaster splint to decrease the postoperative tension of the flap.Results All the flaps survived completely by primary intention but local infection occurred in 2 wounds which was cured by second intention of dressing change.The follow-up periods ranged from 8 to 12 months (average,11.5 months).The scar around the flap was remarkable in 2 cases,but the flaps in the other cases appeared normal in terms of color and texture.The ankle function was satisfactorily normal in all the cases.Conclusion Our self-designed rectangle advancement flaps provide a simple,safe and reliable way to repair skin defects around the Achilles tendon in children.

Objective To analyze setup errors in cone beam computed tomography(CBCT)-guided radiotherapy for nasopharyngeal cancer(NPC)and evaluate the use frequency of CBCT. Methods Twenty-six patients newly diagnosed with NPC who received CBCT scan no less than 3 times per week during the whole course(7 weeks)of intensity-modulated radiotherapy(IMRT)were enrolled as subjects. Two setup errors were recorded each week:the setup error in the first CBCT analysis(Ef)and the setup error in the subsequent CBCT analysis(Ec). Comparisons of Efbetween two different weeks, Ecbetween two different weeks,and between Efand Ecin the same week were made by analysis of variance. Results During the 7 weeks,there were no significant differences in Efin the medial-lateral(ML), superior-inferior(SI), or anterior-posterior(AP)direction between any two weeks(all P>0.05);there were also no significant differences in Ecin the ML or SI direction between any two weeks(all P>0.05);there was a significant difference in Ecin the AP direction between two different weeks(P<0.05);there were no significant differences between Efand Ecin the ML or SI direction in any week(P>0.05);there were also no significant differences between Efand Ecin the AP direction in any week(P>0.05)except for the first week (P<0.05). Conclusions In IMRT for NPC,the setup errors in the ML and SI directions are stable in the whole course of radiotherapy,while the setup errors in the AP direction are different between the first week and subsequent weeks. Daily CBCT scan in the first week and weekly CBCT scan in the subsequent weeks are highly recommended for most patients to reduce the use frequency of CBCT.