Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Analysis of early and middle stage efficacy and complications of oblique lumbar interbody fusion in treating degenerative lumbar diseases / 中国骨伤

OBJECTIVE@#To investigate the early and middle stage efficacy and complications of minimally invasive extraperitoneal oblique lumbar interbody fusion (OLIF) in the treatment of degenerative lumbar diseases.@*METHODS@#The clinical data of 22 patients with degenerative lumbar diseases underwent OLIF from October 2017 to March 2019 were retrospectively analyzed, including 14 males and 8 females, aged from 51 to 72 years with an average of (63.15±7.22) years. There were 6 cases of lumbar spinal stenosis, 5 cases of lumbar spondylolisthesis, 4 cases of adjacent vertebral disease, 3 cases of degenerative lumbar scoliosis, 3 cases of discogenic low back pain, and 1 case of recurrence after posterior lumbar decompression. Posterior minimally invasive pedicle screw fixation was performed in 13 cases and Stand-alone fixation in 9 cases. Intraoperative blood loss, operation time, postoperative drainage volume, landing time were recorded. The intervertebral disc height(IDH), intervertebral foramen height(IFH), intervertebral foramen area( IFA), canal diameter(CD), canal area(CA) were measured before and after operation. The imaging changes (including location of fusion cage, interbody fusion, and cage subsidence) and complications were observed. Oswestry Disability Index (ODI), numerical rating scales (NRS) and Japanese Orthopaedic Association (JOA) scores were compared before and 3, 6, 12 months after operation.@*RESULTS@#All 22 patients successfully completed the operation. The intraoperative blood loss was 25 to 280 ml with an average of (95.45±79.07) ml and that of simple anterior approach was 25 to 70 ml with an average of (45.71±15.42) ml. The operation time was 75 to 210 min with an average of (137.72±37.66) min, and the simple anterior operation time was 75 to 105 min with an average of (91.40±15.96) min. The total drainage volume was 10 to 110 ml with an average of (56.23±31.15) ml, and the time to go down to the ground was 24 to 72 hours (54.48±18.24) hours after operation. Postoperative IDH improved (6.63±2.61)mm(P<0.05), the IFH improved (5.35±2.47)mm (P<0.05), the IFA improved (97.67±33.58)mm2(P<0.05), the CD improved (3.31±1.61) mm(P<0.05), the CA improved (57.52±31.39) mm2(P<0.05). Five patients got interbody fusion at 6 months after operation and all 22 patients got interbody fusion at 12 months after operation. There was 5 cases of fusion cage subsidence, all of which occurred in the cases without posterior fixation(using Stand-alone fixation). There was no serious complication such as big blood vessel injury, ureter injury, dural sac injury and nerve root injury. Peritoneal injury occurred in 1 case, postoperative transient thigh pain, decrease of quadriceps femoris muscle strength in 4 cases and sympathetic nerve injury in 1 case. The symptoms of lumbago and radicular pain of lower extremities were alleviated obviously 3 days after operation. The ODI, NRS and JOA scores at 6, 12 months after operation were significantly improved(P<0.05).@*CONCLUSION@#The treatment of lumbar degenerative diseases with definite indications by OLIF can achieve satisfactory clinical results, and it has advantages of less intraoperative bleeding, fast time to land, less complications, good imaging improvement and indirect decompression. But the operation time and fluoroscopy time are longer in the early stage, and complications such as peritoneal injury and lumbar plexus over traction may occur. The long-term incidence of settlement of fusion cage with Stand-alone technology is higher.

PrepFiler Express BTATM Lysis Buffer Combined with Silicon Microbeads for Rapid DNA Extraction from Bone / 法医学杂志

Objective To establish a convenient and rapid method for extracting DNA from bone.Methods Fifteen long bone samples were washed and sterilized.The skeletal fragments were obtained by electric drill,and lysed by PrepFiler Express BTATM lysis buffer.DNA was then manually extracted by silicon microbeads for further analysis.Results STR genotyping was successfully obtained in 14 out of the 15 samples,and the detection rate was 93.33％.Conclusion The method for DNA extraction from bone established in present study is convenient,quick,effective,and with a strong applicability,which is worth spreading and applying.

Short hairpin RNA targeting insulin-like growth factor binding protein-3 restores the bioavailability of insulin-like growth factor-1 in diabetic rats

ABSTRACT Purpose To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. Materials and methods After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. Results At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Conclusions Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.

Effects of different endophytic fungi on seedling growth of Dendrobium devonianum / 中国中药杂志

To obtain seedling growth-promoting fungi is a key step in restoration-friendly cultivation of medicinal Dendrobium species, since there are a large number of functionally-unknown endophytic fungi in the roots of Dendrobium plants.In this study, six functionally-unknown endophytic fungal strains were isolated from roots of D.devonianum using single peleton isolation technology, and used in inoculation experiments to test their effectiveness for seedling growth in D.devonianum.After 90 days of inoculation, comparing with the control treatment, FDdS-1, FDdS-2 and FDdS-4 showed strong pathogenic or fatal effects on seedlings; while, FDdS-12, FDdS-9 and FDdS-5 had different effects on seedling growth.FDdS-5 had significant promoting effects on height, fresh and dry weight, stem diameter and root numbers, while FDdS-9 only had significant promoting effect on seedling height, and FDdS-12 had a negative effect on seedling growth.According to the anatomical features of the inoculated roots, FDdS-5 fungi could infect the velamina of seedlings and the existence of symbiosis pelotons in the cortex cells, suggesting that FDdS-5 is a mycorrhiza fungi of D.devonianum.FDdS-5 and FDdS-9 were identified as Sebacina vermifera and Sebacina sp.by molecular technologies.By using FDdS-5 in the restoration-friendly cultivation of D.devonianum, it could effectively promote seedling growth and shorten the seedling growth periods.The results will aid in reintroduction and cultivation of D.devonianum.

Recurrence and survival analysis of postoperative patients aged 25 to 59 years with differentiated thyroid carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the recurrence and survival of postoperative patients with differentiated thyroid carcinoma (DTC) aged from 25 to 59 years.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 36 patients with DTC treated in our hospital from 1996 to 2011, and the recurrence and survival status of the patients were recorded. Kaplan-Meier analysis was carried out to analyze factors that affect the patient's survival.</p><p><b>RESULTS</b>Nine patients died of recurrence or metastasis, and the interval between the initial surgery and recurrence ranged from 22 to 46 months. The survival time of the 36 patients ranged from 34 to 135 months with a 10-year survival rate of 75.0%. Kaplan-Meier analysis showed that male patients had a significantly shorter mean survival time than female patients (Χ=3.164, P=0.041); the median survival time of patients aged 45-59 years was obviously shorter than that of patients aged 25-44 years (Χ=4.622, P=0.032); the postoperative survival in patients with 131I therapy was significantly longer than those who did not receive the therapy (Χ=4.527, P=0.033), and was not affected by total excision of the thyroid gland (Χ=0.988, P=0.320). No significant difference was found in the median survival of patients in different clinical stages (Χ=2.2132, P=0.167).</p><p><b>CONCLUSION</b>In young and middle-aged patients with DTC, postoperative recurrence is the most likely in 2 to 4 years after the surgery. Male patients at 45-59 years of age who do not receive 131I treatment are at high risks of tumor recurrence.</p>

Comparative study on pro-inflammatory toxicity of Pinellia pedatiecta before and after being processed with alum / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the pro-inflammatory toxicity of Pinellia pedatiecta, as well as the alum processing method on its pro-inflammatory effect.</p><p><b>METHOD</b>Raphide and agglutinin (PPA) proteins were isolated from fresh P. pedatiecta. The overall animal and cellular level models were applied to investigate the pro-inflammatory effect of raphide and PPA in P. pedatiecta, as well as the impact of the alum processing method on the pro-inflammatory effect, with inflammatory mediators as the index.</p><p><b>RESULT</b>Intraperitoneal injection with P. pedatiecta raphide suspension could significantly increase the content of inflammatory mediators PGE2 and NO. After the alum processing method was adopted, fresh P. pedatiecta and raphide-induced PGE2 and NO release significantly reduced. The stimulation of mice macrophages with P. pedatiecta agglutinin protein could cause the content of dose-dependent inflammatory mediators TNF-alpha and IL-6. After the alum processing method was adopted, PGE2 content in P. pedatiecta agglutinin protein-induced mice peritoneal exudate notably decreased.</p><p><b>CONCLUSION</b>The irritation and toxicity of P. pedatiecta were inflammatory responses in organisms. Its raphide and agglutinin proteins were toxic components, both could cause significant the release of inflammatory medium. The alum processing method could help significantly reduce the pro-inflammatory toxicity of P. pedatiecta.</p>

Arthroscopic simultaneous reconstruction of posterior cruciate ligament using double femoral tunnel technique and anterior cruciate ligament with achilles allograft / 中华外科杂志

<p><b>OBJECTIVES</b>To introduce the technique of arthroscopic simultaneous reconstruction of posterior cruciate ligament (PCL) using double femoral tunnel, single-bundle transtibial tunnel PCL technique and anterior cruciate ligament (ACL) with achilles allograft, and to evaluate the clinical outcome.</p><p><b>METHODS</b>Fourteen patients with PCL and ACL injuries after a minimum follow-up 18 months were received. Arthroscopically assisted simultaneous ACL/PCL reconstruction with achilles allograft were performed using the single-incision endoscopic ACL technique and the double femoral tunnel, single-bundle transtibial tunnel PCL technique. The Lysholm and Tegner knee score scale were used for functional evaluation. All patients were evaluated with physical examination and KT-1000 arthrometer testing. The mean knee flexion was (123.6 +/- 2.5) degrees preoperatively. The Lysholm score was 52.8 +/- 2.2. The Tegner score was 5.9 +/- 0.5 before injury, 1.2 +/- 0.9 preoperatively.</p><p><b>RESULTS</b>The mean time from injury to the reconstructive procedure was 19.5 d. The mean knee flexion was (117.9 +/- 2.8) degrees postoperatively( t = 1.54, P = 0.14). As to the Lachman test for 14 patients, the results of 13 patients (92.9%) was negative. As to posterior drawer test, the results of 12 patients (85.7%) was negative. The Lysholm score was 92.9 +/- 3.3 at final evaluation (t = 17.009, P < 0.001). KT-1000 arthrometer testing at 25 degrees knee flexion showed that the side-to-side difference was below 2 mm in 9 cases, 3-5 mm in 4 cases, 6 mm in 1 case. At 75 degrees knee flexion the difference was below 2 mm in 10 cases, 3-5 mm in 3 cases, 6 mm in 1 case. The Tegner score was 5.4 +/- 0.8 at final evaluation. The difference between the preoperative score and the postoperative was statistically significant (F = 4.2, P < 0.01).</p><p><b>CONCLUSIONS</b>Combined ACL and PCL injuries can be successfully treated with arthroscopic simultaneous reconstruction of PCL using double femoral tunnel technique and ACL with achilles allograft. The double femoral tunnel technique more closely approximates the anatomic insertion the native PCL. Most patients recover a functionally stable knee.</p>

A cadaveric study of relationships among rotational alignment reference axes of distal femur and tibial mechanical axis / 中华外科杂志

<p><b>OBJECTIVES</b>To investigate the relationships among rotational alignment reference axes of distal femur and tibial mechanical axis, and determine the safest rotational alignment reference axis.</p><p><b>METHODS</b>Digital photos were taken of 30 cadaveric lower extremities with knee in extension and flexion at 90 degrees , angles were measured among tibial mechanical axis and a line perpendicular to clinical epicondylar axis, a line perpendicular to surgical epicondylar axis, Whiteside's line and femoral mechanical axis. Statistical analysis of relationships among those axes were performed.</p><p><b>RESULTS</b>The angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, a line perpendicular to the surgical epicondylar axis, Whiteside's line and femoral mechanical axis were 0.6 degrees varus, 3.9 degrees varus, 0.2 degrees valgus and 3.0 degrees varus respectively. The angle between the femoral mechanical axis and the tibial mechanical axis was significantly larger than the angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, the Whiteside's line (P < 0.05). There was no significant difference compared with the angle between a line perpendicular to the surgical epicondylar axis and the tibial mechanical axis. Angles of the clinical epicondylar axis, the surgical epicondylar axis and the Whiteside's line between knee extension and flexion were 2.3 degrees valgus, 0.9 degrees varus and 3.1 degrees valgus respectively.</p><p><b>CONCLUSION</b>The surgical epicondylar axis rather than the clinical epicondylar axis or the Whiteside's line is the safest femoral rotational alignment reference axis intraoperatively.</p>

Effect of increased posterior tibial slope or partial posterior cruciate ligament release on knee kinematics of total knee arthroplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the effects of increased posterior tibial slope or partial posterior cruciate ligament (PCL) release on knee kinematics of total knee arthroplasty (TKA).</p><p><b>METHODS</b>Anteroposterior laxity, rotational laxity, varus and valgus laxity and maximum flexion angle were evaluated in 6 normal cadaver knees and the knees after TKA at flexion 0 degrees , 30 degrees , 60 degrees , 90 degrees and 120 degrees . Then the femoral prosthesis was shifted 5 mm posteriorly to simulate the tightly implanted knee. The same tests were performed on the tightly implanted knees. After that, the posterior tibial slope was increased 4 degrees or the PCL was partially released, and the same tests were made as in the normal knees respectively. Statistical analysis of the results was made using student's t test.</p><p><b>RESULTS</b>Anteroposterior laxity, rotational laxity and varus and valgus laxity of the tightly implanted knees at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees were significantly less than those of the normal TKA knees (P < 0.05). Compared with the tightly implanted knees, anteroposterior laxity, rotational laxity and varus and valgus laxity at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees significantly improved after increased 4 degrees posterior tibial slope (P < 0.05); in the partial PCL released group, anteroposterior laxity at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees was significantly improved (P < 0.05), varus and valgus laxity was significantly improved only at flexion 90 degrees (P < 0.05), and rotational laxity was significantly improved at flexion 30 degrees , 60 degrees and 90 degrees (P < 0.05). Compared with PCL released group, varus and valgus laxity at flexion 30 degrees , 60 degrees and 90 degrees and rotational laxity at flexion 0 degrees , 30 degrees , 60 degrees and 90 degrees were significantly improved in the group of increased 4 degrees posterior tibial slope (P < 0.05). Maximum flexion angle of the tightly implanted knee (120.4 degrees ) was less than that of the normal TKA knees (130.3 degrees , P < 0.05) and that of increased 4 degrees posterior tibial slope group (131.1 degrees , P < 0.05). There was no significant difference at the maximum flexion angle between the increased 4 degrees posterior tibial slope group and the PCL released group (131.1 degrees vs 124.0 degrees , P = 0.0816).</p><p><b>CONCLUSIONS</b>Anteroposterior laxity, varus and valgus laxity, rotational laxity and maximum flexion angle of the tightly implanted knees are less than those of the normal TKA knees. After increased 4 degrees posterior tibial slope, these indexes are improved significantly. Partial PCL released can significantly improve the anteroposterior laxity and had less effect on the varus and valgus laxity, rotational laxity and maximum flexion angle. So, a knee that is tight in flexion can be more likely to be corrected by increasing posterior tibial slope than by partially releasing PCL.</p>

The incidence and variation of tunnel enlargement after anterior cruciate ligament reconstruction / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the incidence and variation of tunnel enlargement after anterior cruciate ligament (ACL) reconstruction.</p><p><b>METHODS</b>ACL reconstructions using hamstring tendons were performed in 58 patients (58 knees) in the study. MRI scans were taken in a consistent manner at 1, 3, 6, 12 and 24 months after surgery to measure tibial and femoral tunnel expansion.</p><p><b>RESULTS</b>Femoral tunnel enlargement was observed in 9 knees (9/58, 15.5%); Tibial tunnel enlargement was found in 12 knees (12/58, 20.7%). Of those with enlarged bone tunnels, there was no significant difference of tunnel diameters between 1 and 3 months after surgery (P>0.05). Six, 12 and 24 months postoperatively, the average tunnel diameters were larger than those of 1 or 3 months after surgery (P<0.05), however, no significant difference was found in between the tunnel diameters 6, 12 and 24 months postoperatively either (P>0.05).</p><p><b>CONCLUSION</b>Tunnel expansion mainly occurs during 3 to 6 months after surgery, and it remains basically unchanged between 12 and 24 months postoperatively.</p>

Recent advances in the study of antifungal lead compounds with new chemical scaffolds / 药学学报

In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized.