ObjectiveTo investigate the value of percutaneous and intravenous contrast-enhanced ultrasound（P-Ⅳ-CEUS） in sentinel lymph nodes（SLNs） after resection of early-stage primary breast cancer. MethodsA retrospective analysis was done on the clinical and imaging data of 42 early breast cancer patients. Following primary tumor resection， all these patients underwent reoperation in our hospital. SLNs were examined by preoperative P-Ⅳ-CEUS and intraoperative sentinel lymph node biopsy（SLNB） was performed by using Methylene blue as a tracer. Then we analyzed the detection and false-negative rate in CEUS and SLNB respectively. By using the surgical pathological results as the gold standard， the diagnostic efficacy of CEUS for SLNs was explored. ResultsThe detection rate and false negative rate of SLNs in percutaneous contrast-enhanced ultrasound （P-CEUS） were 92.9% （39/42） and 7.1% （3/42）， respectively. The detection rate in methylene blue staining was 100% （41/41） and one patient underwent neoadjuvant therapy due to biopsy-confirmed metastasis. The sensitivity， specificity， positive predictive value， negative predictive value and accuracy of P-Ⅳ-CEUS were 66.7% （2/3）， 100% （37/37）， 100% （2/2）， 97.3% （36/37） and 97.4% （38/39）， respectively. ConclusionsP-Ⅳ-CEUS after resection of early-stage primary breast cancer can accurately detect SLNs and characterize their status， which is a reliable clinical basis for reducing invasive SLNB.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Background: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. Methods: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. Results: There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). Conclusion Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

[摘 要] 目的：探讨胶质母细胞瘤（GBM）患者肿瘤组织来源的GBM类器官（GBO）模型的制备方法。方法：选取2021年广东三九脑科医院新诊断经病理确诊的8例GBM患者的新鲜肿瘤组织标本，将其剪成0.5~1 mm大小的组织碎片并用特制的培养基进行培养，待其成球且直径达到1 mm时剪小传代，同时选取培养2周以上的GBO进行石蜡包埋、切片，后进行H-E染色和免疫组化染色检测，并与亲本GBM组织进行组织学与细胞学的比较。结果：成功培养2例可传代冻存的GBO，并建立GBO生物库。H-E染色结果显示，GBO保留了与亲本GBM组织相似的组织结构和细胞形态；免疫组化实验结果显示，GBO与GBM组织中GFAP、OLIG2、Ki67和ATRX分子的表达情况一致。结论：将患者来源的GBM组织在体外剪小并用特制培养基培养，可构建与GBM患者肿瘤组织在组织和细胞层面一致的GBO。

OBJECTIVE: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema. METHODS: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up. RESULTS: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average. CONCLUSION 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.
Acne Vulgaris/therapy* ; Erythema/etiology* ; Face ; Humans ; Immunoglobulin A ; Treatment Outcome

OBJECTIVE: To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA). METHODS: A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. RESULTS: A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study. CONCLUSIONS CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).
Humans ; Medicine, Chinese Traditional ; Osteoarthritis, Knee/therapy* ; Outpatients ; Quality of Life ; Treatment Outcome

OBJECTIVE: To investigate the types and proportion of gene mutations of thalassemia in Hakka people in Gannan Area of Jiangxi, and to provide some references for prevention and treatment of thalassemia major, genetic counseling and epidemiological studies. METHODS: 81 cases Hakka patients with severe thalassemia admitted treated in First Affiliated Hospital of Gannan Medical College from January 2009 to June 2019 were enrolled. The deletion type of α-thalassemia was detected by Gap-PCR. The point mutations of α-thalassemia and β-thalassemia were detected by PCR-RDB. The thalassemia gene was detected and analyzed in the patients with anemia, and the frequency of gene mutation was calculated. RESULTS: Among 81 Hakka patients with thalassemia major, 4 β-thalassemia (homozygote) genotypes were detected out, including: CD41-42（TTCT）(19 cases), β-IVS-II-654 (C→T) (9 cases), -28M (A→G) (1 case), CD17 (A→T) (1 case); 12 β-thalassemithalassemia (heterozygote) genotypes were detected out, including: CD41-42(-TTCT)/β-IVS-II-654(C→T) (15 cases, 29.41%), β-IVS-II-654(C→T)/β-28M(A→G) (13 cases，25.49%) ； CD41-42(-TTCT)/β-28M(A→G) (9 cases，17.65%); β-IVS-II-654(C→T) /CD27/28(+C) (3 cases， 5.88%) ； CD41-42(-TTCT)/CD27/28(+C)(3 case，5.88%)；β-28M(A→G)/CD17(A→T) (2 cases，3.92%)；CD41-42(-TTCT)/CD17(A→T), CD41-42(-TTCT)/Βe, β-IVS-II-654(C→T)/β-29、βCD17（A→T）/CD71-72(+a), βCD71-72/β-28M(A→G), β-28M(A→G) /β-IVS-II-654(C→T)(1 cases，1.96%). There were 3 cases of β homozygous thalassemia with α-thalassemia gene and 5 cases of β heterozygotes thalassemia with α-thalassemia gene. CONCLUSION The incidence rate of thalassemia in Hakka people in Gannan Area of Jiangxi is relatively high. The distribution of gene mutation types is as follows: the genotype of CD41-42 (-TTCT) is the main genotype of β-thalassemia (homozygous); the major genotypes of β- thalassemia (heterozygotes) are CD41-42 (-TTCT)/β-IVS-II-654 (C→T) and β-IVS-II-654 (C→T) /β-28M (A→G); CD41-42 (-TTCT) gene is dominant in β-complex α-thalassemia.
China ; Genotype ; Heterozygote ; Humans ; Mutation ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

OBJECTIVE: To explore a new method in order to extract DNA from bones and teeth automatically. METHODS: Samples of 33 bones and 15 teeth were acquired by freeze-mill method and manual method, respectively. DNA materials were extracted and quantified from the triturated samples by AutoMate Express forensic DNA extraction system. RESULTS: DNA extraction from bones and teeth were completed in 3 hours using the AutoMate Express forensic DNA extraction system. There was no statistical difference between the two methods in the DNA concentration of bones. Both bones and teeth got the good STR typing by freeze-mill method, and the DNA concentration of teeth was higher than those by manual method. CONCLUSION AutoMate Express forensic DNA extraction system is a new method to extract DNA from bones and teeth, which can be applied in forensic practice.
Automation ; Bone and Bones/chemistry* ; DNA/isolation & purification* ; DNA Fingerprinting/methods* ; Forensic Medicine/methods* ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; Specimen Handling/methods* ; Tooth/chemistry*