OBJECTIVE To analyze the clinical characteristics of aplastic anemia （AA）/pure red cell aplasia （PRCA） induced by pembrolizumab， and provide reference for clinical safe drug use. METHODS Using search terms as “pembrolizumab”， “keytruda”， “anemia” and “aplastic anemia” in both Chinese and English， the literature related to AA/PRCA induced by pembrolizumab were retrieved from PubMed， Embase， CNKI， Wanfang and VIP databases， and then analyzed descriptively and statistically. RESULTS A total of 10 patients were included from 10 literature； among these 10 patients， there were 5 males and 5 females， with 5 patients being aged 65 or above. The primary disease was mainly metastatic melanoma （4 cases）. AA/PRCA occurred 13 d-3 years after the first dose of pembrolizumab. The main clinical manifestations included fatigue， dyspnea， oral/nasal bleeding， diffuse purpura， etc.； 8 cases developed moderate anemia and 2 cases developed severe anemia. After discontinuation and receiving supportive therapy， 5 cases improved， 1 case worsened in anemia， and 4 cases died. CONCLUSIONS When using pembrolizumab in clinical practice， blood routine should be regularly monitored. When AA/PRCA and other related symptoms occur， pembrolizumab should be stopped in time and a therapy regimen should be formulated according to the patient’ condition， to ensure the safety of medication.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

OBJECTIVE To analyze the characteristics of severe cutaneous adverse reactions(SCARs)induced by oral anticoagulants(OACs),and provide a reference for clinical safety of drug use.METHODS Case reports of SCARs caused by OACs(warfarin,apixaban,rivaroxaban,edoxaban,dabigatran etexilate)were retrieved from PubMed,Embase,CNKI,Wanfang Data,VIP and other databases with search terms as"oral anticoagulants""factor Ⅹa inhibitor""direct thrombin inhibitor"and their Chinese equivalents.A descriptive statistical analysis was performed.RESULTS A total of 11 articles were included,involving 11 patients in total,among whom there were 5 males(45.5%)and 6 females(54.5%),with an average age of(59.6±21.5)years.The primary underlying diseases were mainly atrial fibrillation,pulmonary embolism,joint replacement and valve replacement.The OACs involved included warfarin in 3 cases,rivaroxaban in 4 cases,apixaban in 2 cases,and dabigatran etexilate in 2 cases.SCARs occurred from 10 hours to 42 days after treatment,and 7 cases(63.6%)within 10 to 28 days.Among 11 patients,5 cases were diagnosed as drug reaction with eosinophilia and systemic symptoms,4 cases were diagnosed as Stevens-Johnson syndrome or toxic epidermal necrolysis,and 2 cases were diagnosed as acute generalized exanthematous pustulosis.The clinical manifestations mainly included rash,fever and mucosal damage,etc.Except for 1 patient who died of sepsis and diffuse intravascular coagulation,the rest of the patients improved or recovered after withdrawal and treatment with glucocorticoids.CONCLUSIONS SCARs are rare but serious adverse reactions caused by OACs,typically occurring 10 to 28 days after medication.Once SCARs are suspected to be caused by OACs,the medication should be discontinued immediately,and a treatment plan should be formulated based on the type of SCARs to ensure the safety of patients'drug use.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To compare the effect of three-dimensional visual (3DV) model, three-dimensional printing (3DP) model and computer-aided design (CAD) modified 3DP model in video-assisted thoracoscopic surgery (VATS) sublobular resection. Methods The clinical data of patients who underwent VATS sublobular resection in the Affiliated Hospital of Hebei University from November 2021 to August 2022 were retrospectively analyzed. The patients were divided into 3 groups including a 3DV group, a 3DP group and a CAD-3DP group according to the tools used. The perioperative indexes and subjective evaluation of operators, patients and their families were compared. Results A total of 22 patients were included. There were 5 males and 17 females aged 32-77 (56.95±12.50) years. There were 9 patients in the 3DV group, 6 patients in the 3DP group, and 7 patients in the CAD-3DP group. There was no statistical difference in the operation time, intraoperative blood loss, drainage volume, hospital stay time or postoperative complications among the groups (P>0.05). Based on the subjective evaluations of 4 surgeons, the CAD-3DP group was better than the 3DV group in the preoperative planning efficiency (P=0.025), intuitiveness (P=0.045) and doctor-patient communication difficulty (P=0.034); the CAD-3DP group was also better than the 3DP group in the overall satisfaction (P=0.023), preoperative planning difficulty (P=0.046) and efficiency (P=0.014). Based on the subjective evaluations of patients and their families, the CAD-3DP group was better than the 3DP group in helping understand the vessel around the tumor (P=0.016), surgical procedure (P=0.020), procedure selection (P=0.029), and overall satisfaction (P=0.048); the CAD-3DP group was better than the 3DV group in helping understand the tumor size (P=0.038). Conclusion CAD-modified 3DP model has certain advantages in pre-planning, intraoperative navigation and doctor-patient communication in the VATS sublobectomy.

[摘 要] 目的：探讨含SET结构域蛋白5（SETD5）对结肠癌细胞增殖、迁移和对5-氟尿嘧啶（5-FU）药物敏感性的影响及机制。方法：常规培养结肠癌细胞，用Lipofectamine 2000将siSETD5-NC、si-SETD5-1~3质粒转染至HT-29细胞中，将其分为对照组（未处理）、si-SETD5-NC组、si-SETD5组和si-SETD5+SC79组，si-SETD5+SC79组HT-29细胞转染质粒的同时用10 µmol/L SC79处理。qPCR法检测NCM460、HT-29和LoVo细胞中SETD5 mRNA表达，流式细胞术、细胞划痕法、WB法和CCK-8法分别检测各组HT-29细胞的凋亡情况、迁移能力、相关蛋白的表达，以及对5-FU的敏感性。结果：SETD5 mRNA在HT-29、LoVo细胞中均呈高表达（均P<0.01）。在HT-29细胞中成功地敲减了SETD5 mRNA（P<0.01）。敲减SETD5 mRNA可明显抑制HT-29细胞的增殖活性（P<0.01）、迁移能力（P<0.01）、相关蛋白（SETD5、p-PI3K、p-AKT1、p-mTOR蛋白）的表达（均P<0.01）、促进细胞凋亡（P<0.01），且提高其对5-FU的敏感性（P<0.01），这些作用均可被AKT激活剂SC79部分阻挡（P<0.05或P<0.01）。结论：SETD5在HT-29、LoVo细胞中高表达，SETD5通过PI3K/AKT1通路促进结肠癌HT-29细胞的增殖、迁移，且降低其对5-FU的敏感性，SETD5是结肠癌临床诊断、治疗的潜在靶点。

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Objective:To investigate the effects of unilateral ureteral obstruction on renal pelvic peristalsis and pacemaker cells in neonatal rats.Methods:An animal experimental study.Thirty-six 2-day-old newborn SD rats were randomly divided into the partial unilateral ureteral obstruction (PUUO) group, complete unilateral ureteral obstruction (CUUO) group, and sham operation group, with 12 rats in each group.One week after surgery, all rats were subjected to renal pelvic pressure (RPP) measurement by puncture.After measurement, the rats were euthanized, and their left renal pelvis and ureter were removed and fixed for histological examination.Parameters such as RPP, peristaltic wave frequency and amplitude at different perfusion speeds were recorded and compared, and the changes in pacemaker cells (atypical smooth muscle cells and Cajal-like interstitial cells) were also compared.The independent samples t-test was used for comparison between 2 groups, and the one-way ANOVA of variance was used for comparison among 3 groups. Results:In the sham operation group, the RPP increased gradually with the increase of perfusion speed; the frequency of peristaltic waves rose rapidly and then dropped after reaching the highest level with the increase of perfusion speed; similarly, the amplitude of peristaltic waves first increased and then decreased as the perfusion speed increased.In the PUUO group, the RPP increased rapidly with the increase of perfusion speed, higher than that in the sham operation group; the frequency of peristaltic waves was higher than that in the sham operation group, and it was relatively constant under the perfusion speed of 40 mL/h, but when the perfusion speed increased again, the frequency began to decline; the amplitude of peristaltic waves increased quickly and then declined at a faster rate than the sham operation group with the increase of perfusion speed.In the CUUO group, the basic RPP was 12 cmH 2O(1 cmH 2O=0.098 kPa); at the perfusion speed of 5 mL/h, the RPP rose gradually, and no plateau appeared; when the RPP reached 73 cmH 2O, the perfusate retrograded from the side of the puncture needle, then the RPP slightly decreased and then balanced, and no regular peristaltic waves were observed in the renal pelvis throughout the whole perfusion process.Immunofluorescence staining analysis showed the pacemaker cells were all located in the smooth muscle of the renal pelvic wall.The sham operation group had the highest positive rate, followed by the PUUO group and then the CUUO group. Conclusions:Ureteral obstruction has a significant impact on the peristalsis of the renal pelvis, and its impact on the peristaltic wave frequency and amplitude and RPP can be predicted.The reduction of pacemaker cells in the renal pelvis may be involved in the changes of renal pelvic peristalsis caused by ureteral obstruction, but further research is needed on how pacemaker cells regulate the peristalsis of the renal pelvis and ureter.