OBJECTIVE To optimize the system of patent linkage system and provide a reference for encouraging generic drugs to apply for listing. METHODS On the basis of literature research， combined with the author’s work experience， the situation of generic drug application and patent challenge were analyzed comparatively after the implementation of the patent linkage system in China. Based on the patent linkage system， the reasons for the insufficient incentive for the challenge of generic drug patents in China were analyzed； corresponding countermeasures and suggestions were proposed. RESULTS & CONCLUSIONS The patent linkage system in China was implemented in 2021， but due to the implementation of the system being still in its initial stage， the relevant documents for practical guidance are not yet complete， and the supporting incentive mechanism is not yet sound， resulting in a weak willingness of generic pharmaceutical enterprises to initiate patent challenges. It is suggested that China can further improve the patent linkage system by improving the patent information registration platform of generic drugs， developing professional drug patent agencies， and establishing the patent common challenges platform of the first generic drug， in order to incentivize Chinese generic drug enterprises to increase innovation motivation， challenge original research drug patents， and apply for listing， achieving the effect of suppressing drug prices and benefiting the people through full competition.

Objective:To evaluate our self-designed pubic symphysis orthotic compression anatomic plate (PSOCAP) in the treatment of fractures and dislocations around the pubic symphysis.Methods:A retrospective study was conducted to analyze the 16 patients with fracture or dislocation around the pubic symphysis who had been treated by our self-designed PSOCAP at Department of Traumatic Surgery, Center for Orthopaedic Surgery, The Third Hospital Affiliated to Southern Medical University from January 2021 to June 2022. There were 8 males and 8 females with an age of (41±19) years. According to the Tile classification for pelvic fractures, there were 3 cases of type B1, 2 cases of type B3, 1 case of type C1.2, 4 cases of type C1.3, 3 cases of type C2, and 3 cases of type C3. There were 8 cases of pubic symphysis separation and 8 fractures of the pubic ramus (2 ones at Nakatani zone Ⅰ and 6 ones at Nakatani zone Ⅱ). Time from injury to surgery was 16 (11, 53) days, ranging from 4 to 348 days. The fractures or dislocations around the pubic symphysis were exposed by the modified Stoppa approach, reduced with the assistance of PSOCAP and fixated with PSOCAP; the posterior pelvic ring was reduced and fixated by corresponding surgical methods. Recorded were the surgical time, intraoperative bleeding, postoperative quality of fracture reduction, surgical complications, and functional recovery at the last follow-up concerning the pelvic anterior ring.Results:Surgery went on successfully in the 16 patients. Their surgical time was (58±15) min, ranging from 40 to 90 min, and their intraoperative bleeding 85 (63, 150) mL, ranging from 50 to 250 mL. According to the Matta scoring, the fracture reduction was evaluated as excellent in 10 cases, as good in 3 cases and as fair in 3 cases. The (10±3)-month follow-up for the 16 patients revealed complete fracture union for all after (12±2) weeks. According to the Majeed scoring at the last follow-up, the pelvic function was evaluated as excellent in 5 cases, as good in 7 cases, and as fair in 4 cases. No such postoperative complications as fracture displacement or internal fixation failure occurred.Conclusion:Owing to the biplane and integrated structure, our self-designed PSOCAP can help reduce the fractures or dislocations around the pubic symphysis to achieve anatomical reduction and strong internal fixation, leading to good clinical efficacy.

Objective:To investigate the surgical technique and the clinical effects of direct posterior approach (DPA) with the fixation of percutaneous tunnel screw and plate for acetabular posterior comminuted fractures.Methods:Thirty-six cases with acetabular posterior comminuted fractures treated by this technique from January 2016 to July 2020 were retrospectively analyzed in this study. There were 28 males and 8 female, aged 42.0±12.1 (range 19-64) years. According to Letournel-Judet classification, there were 28 cases of transverse associated with posterior wall fractures, 6 cases of posterior column with posterior wall fractures and 2 cases of T shape with posterior wall fractures. DPA was adopted in prone position. The anterior and posterior column fractures of the acetabulum were reduced under direct vision and then fixed with percutaneous tunnel screw. Further, the posterior wall fractures of the acetabulum were reduced and fixed with plate and screws. The operation duration, intraoperative blood loss, incision length, fracture union time, fracture reduction quality, postoperative complications and hip function were recorded.Results:The incision was 9.8±1.2 (range 8-12) cm. The operation duration was 102.9±21.4 (range 65-145) min. Intraoperative bleeding was 214.0±116.9 (range 100-640) ml. Postoperative X-ray and CT examinations showed perfect reduction. All the patients were followed up for 20.9±9.2 (range 10-38) months. The fracture healing time was 4.6±1.0 (range 3-6) months. There was no patient with damaged superior gluteal nerve and blood vessel. There were 2 cases of femoral head cystic changes without pain in walking, 1 case of postoperative infection and bacteremia who was cured at 1 month after debridement and anti-infection treatment, 1 case of sciatic nerve injury but recovered at 3 months after operation, and 1 case of heterotopic ossification at 3 months after surgery without affecting hip motion. According to the Matta's criteria, the reduction quality of the acetabular fracture was rated as excellent in 28 cases, good in 6 cases, fair in 2 cases. According to the modified Merle D'Aubigné and Postel scoring system, hip joint function was excellent in 24 cases, good in 10 cases and fair in 2 cases.Conclusion:DPA approach can directly reduce acetabular posterior comminuted fractures through a minimal incision. Combined with the technique of percutaneous tunnel screw, it displays great advantages of less trauma and with good clinical effects.

Objective:To establish the classification system of sacroiliac joint dislocation with ipsilateral sacral wing fracture (SJDISWF), examine its reliability and evaluate the clinical application.Methods:A multi-center retrospective case series study was conducted to analyze the clinical data of 20 SJDISWF patients admitted to Third Affiliated Hospital of Southern Medical University, Honghui Hospital Affiliated to Xi′an Jiaotong University and Third Hospital of Hebei Medical University from January 2016 to December 2019. There were 8 males and 12 females, aged from 13-58 years［(34.7±13.2)years］. Based on the direction of sacral displacement, SJDISWF was divided into 3 types. Type I: the sacroiliac joint dislocated and the ipsilateral sacral wing fracture fragment was anteriorly prolapsed; Type II: the sacroiliac joint dislocated, the ipsilateral sacral wing fracture fragment was compressed or crushed, the anterior sacral foramen may fractured; Type III: the sacroiliac joint dislocated and the ipsilateral sacral wing fracture end was inserted into the sacral canal, causing an intra-sacral canal occupation. The reliability of the classification was performed based on the assessment results of two phases in four observers at 4-week intervals. Treatments were utilized based on the types I, II, III fractures, including anterior approach for open reduction and internal fixation, closed reduction and internal fixation or posterior approach for open reduction and internal fixation respectively. Postoperative fracture healing time was recorded. Quality of fracture reduction was graded according to Matta′s criteria. Majeed functional score was recorded at postoperative 3 months, 6 months and the final follow-up. Complications were detected as well.Results:The overall Kappa value of inter-observer reliability was 0.890. The overall Kappa value of intra-observer reliability was 0.854. There were 12 patients with type I, 7 with type II and 1 with type III. All patients went through the procedure uneventfully and were followed up for 6-36 months［(20.0±8.7)months］. All patients achieved clinical healing in 8-14 weeks［(10.2±1.7)weeks］. According to the Matta′s criteria for fracture reduction, the outcome was excellent or good in 83% (10/12) for type I, 71% (5/7) for type II and 0% (0/1) for type III, with the overall excellent rate of 75%. Majeed functional score was (74.6±5.2)points at postoperative 3 months and (84.4±5.8)points at postoperative 6 months ( P<0.01). According to Majeed functional score, the outcome was excellent or good in 75% (9/12) for type I, 100% (7/7) for type II and 0% (0/1) for type III at the final follow-up, with the overall excellent rate of 80%. There were no complications such as lateral femoral cutaneous nerve or sciatic nerve injury, lower extremity deep vein thrombosis, sacroiliac joint pain, failure of internal fixation or loss of fracture reduction during the follow-up. Conclusions:The SJDISWF classification has high reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory restoration and functional recovery, indicating that the classification plays a certain role in guiding treatment selection for SJDISWF.

Objective:To investigate the surgical method of LC-II screws for fragility fractures of the pelvis (FFP) in the elderly and evaluate its clinical efficacy.Methods:A retrospective analysis was performed on 45 patients with FFPs operated in our department from January 2011 to January 2022. The clinical information was as follows. The FFP classification of pelvic fracture was IIIA in 26 cases and IIIB in 19 cases. Among them, 22 cases were fixed with closed reduction and modified LC-II screws (experimental group), and 23 cases were fixed with open reduction and reconstruction plates (control group). In the experimental group, there were 6 males and 16 females. The age range was 62-90 years, with an average of 73.2±9.2 years. The FFP classification of pelvic fracture was IIIA in 12 cases and IIIB in 10 cases. In the control group, there were 8 males and 15 females. The age range was 60-87 years, with an average of 72.8±6.6 years. FFP classification of pelvic fracture was IIIA in 14 cases and IIIB in 9 cases. After admission, pelvic X-ray and CT scan were performed, and the surgery was prepared. In the experimental group, after closed reduction of the posterior ring, the modified LC-II screw was inserted below the anterior inferior iliac spine (AIIS) toward the sacroiliac joint and penetrated the sacroiliac joint. For combined anterior ring fractures, the INFIX was used for anterior ring fixation. In the control group, the posterior ring was fixed with a reconstruction plate and/or sacroiliac screw after open reduction through the lateral rectus approach (LRA). The clinical efficacy was evaluated between the experimental group and the control group.Results:All 45 patients were successfully operated and followed up for 6 months to 3 years. All the pelvic fractures healed. In the experimental group of 22 cases, the time from injury to operation was 3-9 days, with an average of 5.8±1.9 days; the operation time was 25-70 min, with an average of 42.0±12.9 min. The intraoperative bleeding was 20-40 ml, with an average of 29.1±6.7 ml. According to the X-ray reduction evaluation criteria of Matta, 7 cases were excellent, 11 cases were good and 4 cases were medium, with an excellent and good rate of 81.8%. According to rehabilitation criteria of Majeed, 10 cases were excellent, 6 cases were good and 6 cases were fair, with a total excellent and good rate of 72.7%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 10 cases, <3 in 7 cases, and 4-6 in 5 cases. No internal fixation loosening occurred. In the control group, the time from injury to operation was 5-20 days, with an average of 9.9±3.8 days; the operation time was 50-150 min, with an average of 89.1±29.5 min; the intraoperative bleeding was 220-1 000 ml, with an average of 509.2±214.3 ml. According to the X-ray reduction evaluation criteria of Matta, 16 cases were excellent, 4 cases were good and 3 cases was medium, with an excellent and good rate of 87.0%. According to rehabilitation criteria of Majeed, 12 cases were excellent, 6 cases were good and 7 cases were fair, with a total excellent and good rate of 78.3%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 14 cases, <3 in 6 cases, and 4-6 in 3 cases. In the control group, posterior ring plate loosening was found in 2 cases and anterior ring pubic ramus plate and screw loosening was found in 4 cases, but there was no reduction loss.Conclusion:The modified LC-II screw is theoretically feasible in the treatment of FFP. Preliminary clinical results show good safety and efficacy, providing a new idea for minimally invasive treatment of FFP.

【Objective】 To analyze the infectious indicators, HBV s gene mutations and changes in bioinformatics characteristics of HBV DNA+ /HBsAg- blood donor. 【Methods】 A sample of HBV DNA+ /HBsAg- was screened by PCR method, and HBsAg/HBsAb/HBeAg/HBeAb/HBcAb of HBV in the sample were detected by ELISA and chemiluminescence methods. The mutation of the HBVs gene fragment in the sample was sequenced and analyzed, and the bioinformatics analysis was performed using analysis software. 【Results】 The sample showed HBV DNA+, HBsAg-, HBsAb+, HBeAg+, HBeAb- and HBcAb+, with an amino acid unit point mutation (P151L) occurred in the HBV s gene, and the spatial structure changed. 【Conclusion】 The spatial structural changes in the gene sequence of HBVs may be the reason for the appearance of serological HBsAg-/HBsAb+ /HBV DNA+ in the test results.

As the only translational factor that plays a critical role in two translational processes (elongation and ribosome regeneration), GTPase elongation factor G (EF-G) is a potential target for antimicrobial agents. Both Mycobacterium smegmatis and Mycobacterium tuberculosis have two EF-G homologous coding genes, MsmEFG1 (MSMEG_1400) and MsmEFG2 (MSMEG_6535), fusA1 (Rv0684) and fusA2 (Rv0120c), respectively. MsmEFG1 (MSMEG_1400) and fusA1 (Rv0684) were identified as essential genes for bacterial growth by gene mutation library and bioinformatic analysis. To investigate the biological function and characteristics of EF-G in mycobacterium, two induced EF-G knockdown strains (Msm-ΔEFG1(KD) and Msm-ΔEFG2(KD)) from Mycobacterium smegmatis were constructed by clustered regularly interspaced short palindromic repeats interference (CRISPRi) technique. EF-G2 knockdown had no effect on bacterial growth, while EF-G1 knockdown significantly retarded the growth of mycobacterium, weakened the film-forming ability, changed the colony morphology, and increased the length of mycobacterium. It was speculated that EF-G might be involved in the division of bacteria. Minimal inhibitory concentration assay showed that inhibition of EF-G1 expression enhanced the sensitivity of mycobacterium to rifampicin, isoniazid, erythromycin, fucidic acid, capreomycin and other antibacterial agents, suggesting that EF-G1 might be a potential target for screening anti-tuberculosis drugs in the future.
Antitubercular Agents/pharmacology* ; Bacterial Proteins/metabolism* ; Drug Resistance ; Mycobacterium smegmatis/metabolism* ; Peptide Elongation Factor G/pharmacology*

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
Apoptosis ; drug effects ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Humans ; Ligands ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; genetics ; metabolism ; Oximes ; metabolism ; pharmacology ; Protein Conformation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrazoles ; metabolism ; pharmacology ; Retinoid X Receptor alpha ; chemistry ; genetics ; metabolism ; Thiazoles ; metabolism ; pharmacology ; Transcription, Genetic ; drug effects ; Transcriptional Activation ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism