Objective:To investigate the effects and mechanism of Jianpi Yangzheng Xiaozheng Prescription in lung pre-metastatic niche formation of gastric cancer by regulating the content of programmed death receptor ligand 1 (PD-L1) in gastric cancer exosomes.Methods:Totally 30 615 mice were divided into normal group, model group, Jianpi Yangzheng Xiaozheng Prescription low- and high-dosage groups, and exosome inhibitor group according to random number table method, with 6 mice in each group. The mouse model of lung pre-metastatic niche formation of gastric cancer was established by tail vein injection of MFC cells. After 12 days of administration, the lung metastasis under the intervention of Jianpi Yangzheng Xiaozheng Prescription was evaluated by observing the infiltration of tumor into lung tissue, weighing lung weight and hematoxylin-eosin (HE) staining of lung tissue. Mouse serum exosomes were extracted by ExoQuick kit and identified by transmission electron microscopy and nanoparticle tracking analysis (NTA). The content of PD-L1 in serum exosomes and the expression levels of serum transforming growth factor-β (TGF-β), interleukin-10 (IL-10) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the phenotype of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) and the expression of PD-L1 in MDSC and TAM.Results:Compared with the model group, after the intervention of Jianpi Yangzheng Xiaozheng Prescription, the lung metastases of mice were reduced ( P<0.05), and the weight of metastatic tumors decreased ( P<0.05). PD-L1 in serum exosomes and the proportion of MDSC and M2 TAM in lung tissue microenvironment decreased, as well as the expression of PD-L1 on MDSC and TAM decreased ( P<0.05). The serum levels of IL-10 and IL-6 significantly decreased ( P<0.05). Conclusion:Jianpi Yangzheng Xiaozheng Prescription can reduce the proportion of MDSC and M2 TAM and the expression level of PD-L1 in the microenvironment of lung tissue before metastasis by inhibiting the transmission of gastric cancer exosome PD-L1 to MDSC and TAM, and reduce the contents of inflammatory factorsIL-10 and IL-6, so as to play a role in improving the microenvironment before lung metastasis of gastric cancer.

Objective To discuss the clinical efficacy of microwave ablation(MWA)combined with percutaneous vertebroplasty(PVP),radiofrequency ablation(RFA)combined with PVP,and simple PVP in the treatment of vertebral metastatic tumors.Methods A total of 65 patients with vertebral metastatic tumors,who were admitted to the Northern Jiangsu People's Hospital of China to receive treatment from January 2019 to June 2023,were enrolled in this study.The patients were divided into MWA plus PVP group(M+P group,n=25,27 diseased vertebral bodies in total),RFA plus PVP group(R+P group,n=20,23 diseased vertebral bodies in total),and simple PVP group(P group,n=20,24 diseased vertebral bodies in total).Visual analog scale(VAS)score was used to assess the preoperative pain degree and the postoperative relief degree.Bone cement distribution and leakage at one week after surgery were evaluated.Results Successful operation was accomplished in all of the patients.No serious procedure-related complications occurred in all the patients of three groups.In R+P group,P group and M+P group,the preoperative mean VAS scores were(8.48±0.80)points,(8.57±0.98)points and(8.20±1.00)points respectively;the differences among the three groups were not statistically significant(P＞0.05).One week after operation,the pain was significantly relieved in all the patients of three groups;the mean VAS scores in R+P group,P group and M+P group were(4.10±0.85)points,(3.17±0.93)points and(2.44±1.23)points respectively,and the reduction in VAS score was most pronounced in M+P group(P＜0.05).Six months after operation;the mean VAS scores in R+P group,P group and M+P group were(1.87±0.84)points,(4.60±1.09)points and(1.48±0.71)points respectively;and the reduction in VAS score was most pronounced in the M+P group(P＜0.05).The used amount of bone cement in M+P group,R+P group and P group was(7.54±1.44)mL,(5.48±1.12)mL and(4.59±1.56)mL respectively,the difference among the three groups was statistically significant(P＜0.05).The vascular leakage rate(34.8％)and non-vascular leakage rate(52.2％)in P group were remarkably higher than those in R+P group and in M+P group(P＜0.05).No statistically significant difference in the rate of cement leakage existed between R+P group and M+P group(P＞0.05).Conclusion For the treatment of vertebral metastases,MW A plus PVP is superior to RFA plus PVP in pain relief rate.

Objective To assess early clinical safety and efficacy of transfemoral transcatheter aortic valve replacement (TF-TAVR) for pure aortic regurgitation (PAR). Methods The clinical data of PAR patients who underwent TAVR in Wuhan Asia Heart Hospital and Wuhan Asia General Hospital from January 2018 to October 2022 were retrospectively analyzed. Patients were divided into a TF-TAVR group and a transapical transcatheter aortic valve replacement (TA-TAVR) group. The clinical data of the patients were analyzed. Results A total of 54 patients were enrolled, including 34 males and 20 females with an average age of 74.43±6.87 years. The preoperative N-terminal pro-B-type natriuretic peptide level was lower [808.50 (143.50, 2 937.00) pg/mL vs. 2 245.00 (486.30, 7 177.50) pg/mL, P=0.015], and the left ventricular end-diastolic diameter (56.00±6.92 mm vs. 63.07±10.23 mm, P=0.005) and sinus junction diameter (32.47±4.41 mm vs. 37.65±8.08 mm, P=0.007) were smaller in the TF-TAVR group. There was no death in the two groups during the hospitalization. Only 1 new death within postoperative 1 month in the TF-TAVR group (cerebral hemorrhage). A total of 2 new deaths in the TF-TAVR group (1 patient of sudden cardiac death and 1 of multiple organ failure), and there was no death in the TA-TAVR group within postoperative 3 months. There was 1 new death in the TA-TAVR group (details unknown), and there was no death in the TF-TAVR group within postoperative 6 months. There was no statistical difference between the two groups in the all-cause mortality and the cumulative survival rate during the follow-up period (P>0.05). The incidence of high atrioventricular block was 36.0% in the TF-TAVR group and 10.3% in the TA-TAVR group (P=0.024). There were no significant differences between the two groups in the perivalvular leakage (≥moderate), valve in valve, a second valve implantation, valve migration, cerebrovascular events, major vascular complications, complete left bundle branch block, new permanent pacemaker implantation or transferring to surgery (P>0.05). However, the incidence rates of complete left bundle branch block and new permanent pacemaker implantation were higher in the TF-TAVR group, accounting for 56.0% and 40.0%, respectively. Conclusion TF-TAVR is a safe and feasible treatment for PAR patients, which is comparable to TA-TAVR in the early postoperative safety and efficacy.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

Objective:To investigate the efficacy of arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon in the treatment of chronic lateral ankle instability (CLAI) complicated with multiple ligament laxity.Methods:A retrospective study was conducted to analyze the 34 patients with CLAI plus multiple ligament laxity who had been treated at Foot and Ankle Surgery Center, The Fourth Hospital of Wuhan from March 2014 to December 2021. They were 8 males and 26 females with an age of (32.2±5.6) years. The patients were divided into 2 groups based on their treatment methods. A reconstruction group of 20 cases were treated by arthroscopic reconstruction of the ligament with autologous semitendinosus tendon while a repair group of 14 cases treated by arthroscopic repair of the ligament with the modified Brostr?m procedure. The 2 groups were compared in terms of surgical time, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS) pain score, talar tilt (TT), anterior translation of the talus (ATT), and complications at the last follow-up.Results:The 2 groups were comparable because there were no statistically significant differences in the general data, AOFAS ankle-hindfoot score, VAS pain score, TT, or ATT before surgery between the 2 groups ( P > 0.05). The surgical time for the reconstruction group [(97.5±11.4) min] was significantly longer than that for the repair group [(53.6±10.7) min] ( P < 0.05). All the 34 patients were followed up for (35.4±3.5) months. The TT, ATT, AOFAS ankle-hindfoot score, and VAS pain score at the last follow-up were all significantly improved compared with the preoperative values in both groups ( P < 0.05). The AOFAS ankle-hindfoot score [(90.6±3.6) points], TT (6.0°±1.5°), and ATT [(3.6±1.4) mm] at the last follow-up in the reconstruction group were all significantly better than those in the repair group [(84.1±11.0) points, 8.6°±4.3°, and (6.6±4.1) mm] ( P < 0.05). There was no statistically significant difference in the VAS pain score between the 2 groups at the last follow-up ( P > 0.05). All incisions healed at one stage without such complications as nerve or vascular injury. CLAI recurrence occurred in 5 cases in the repair group, significant worse than that in the reconstruction group (no recurrence) ( P=0.015). Conclusion:In the treatment of CLAI complicated with multiple ligament laxity, arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon can effectively improve ankle function, enhance ankle stability, and reduce recurrence of the condition.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Objective:To summarize the experience of designing transplanted hair based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns.Methods:A retrospective analysis was conducted on clinical data of the patients with eyebrow defects after burns who treated at Hair Transplantation Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences between January 2011 and September 2023. The location and appearance of eyebrow were designed according to the orbital morphology and tissue characteristics. The follicles were extracted by incision of scalps strips and follicle unit excision (FUE) on the donor area of the occipital region near the posterior hairline or the posterior ear hairline. Scalps with scars that needed to be removed or had "dog ear" deformities following scalp expansion surgery that needed to be repaired were also be used as donor sites. The follicles were divided as follicle units (FUs) including single hair. The recipient area was punched with syringe needle of 22 or 22 G to subcutaneous superficial layer. Then the hair shaft was clamped with microforceps and the hairs were transplanted to the defective area to restore the appearance of eyebrow. The density, morphology, direction and scars of the donor sites were observed by following-ups.Results:A total of 197 patients with 282 eyebrows were recruited. There were 133 males and 64 females. The average age was 33.7 (9 to 62) years. There were 17 patients with skin graft transplantation in the eyebrow arch, 33 with flap and expanded flap repair, 36 with eyelid skin grafting, 111 with burn scar healing. A total of 51 patients had complete eyebrow defects on both sides, and 34 had partial defects. Sixty-five patients had complete eyebrow defects on single side, and 47 had partial defects. The amount of hair transplantation was from 53 to 600 FUs on 282 eyebrows. Seventy-five patients extracted follicles with incision of scalps strips and 122 with FUE. The patients were followed up for 9 months to 10 years. Folliculitis were found in 17 patients and completely cured by 75% alcohol disinfection. Nine patients with insufficient density underwent hair transplantation for a second time to increase the density of hairs one year later. And the implanted hairs grew well, which were similar to the shape and direction of normal eyebrows. Transplanted hairs of the rest patients grew well. The direction and appearance were satisfied. The scar in the donor site was not obvious.Conclusion:The transplanted hair should be designed primarily based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns. Then the position of the eyebrow and the bilateral symmetry should be considered. The ideal effect of eyebrow reconstruction would depend on the full consideration of the receipt site.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

Objective:To summarize the experience of designing transplanted hair based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns.Methods:A retrospective analysis was conducted on clinical data of the patients with eyebrow defects after burns who treated at Hair Transplantation Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences between January 2011 and September 2023. The location and appearance of eyebrow were designed according to the orbital morphology and tissue characteristics. The follicles were extracted by incision of scalps strips and follicle unit excision (FUE) on the donor area of the occipital region near the posterior hairline or the posterior ear hairline. Scalps with scars that needed to be removed or had "dog ear" deformities following scalp expansion surgery that needed to be repaired were also be used as donor sites. The follicles were divided as follicle units (FUs) including single hair. The recipient area was punched with syringe needle of 22 or 22 G to subcutaneous superficial layer. Then the hair shaft was clamped with microforceps and the hairs were transplanted to the defective area to restore the appearance of eyebrow. The density, morphology, direction and scars of the donor sites were observed by following-ups.Results:A total of 197 patients with 282 eyebrows were recruited. There were 133 males and 64 females. The average age was 33.7 (9 to 62) years. There were 17 patients with skin graft transplantation in the eyebrow arch, 33 with flap and expanded flap repair, 36 with eyelid skin grafting, 111 with burn scar healing. A total of 51 patients had complete eyebrow defects on both sides, and 34 had partial defects. Sixty-five patients had complete eyebrow defects on single side, and 47 had partial defects. The amount of hair transplantation was from 53 to 600 FUs on 282 eyebrows. Seventy-five patients extracted follicles with incision of scalps strips and 122 with FUE. The patients were followed up for 9 months to 10 years. Folliculitis were found in 17 patients and completely cured by 75% alcohol disinfection. Nine patients with insufficient density underwent hair transplantation for a second time to increase the density of hairs one year later. And the implanted hairs grew well, which were similar to the shape and direction of normal eyebrows. Transplanted hairs of the rest patients grew well. The direction and appearance were satisfied. The scar in the donor site was not obvious.Conclusion:The transplanted hair should be designed primarily based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns. Then the position of the eyebrow and the bilateral symmetry should be considered. The ideal effect of eyebrow reconstruction would depend on the full consideration of the receipt site.

Lung cancer is the most common cancer in China and even in the world, and it is also the main cause of cancer death. Patients with anaplastic lymphoma kinase (ALK) gene alterations have the opportunity to receive molecularly targeted therapies. The inhibitors of anaplastic lymphoma kinase, such as ALK-tyrosine kinase inhibitors (ALK-TKIs) significantly prolong the survival of patients. ALK gene variant types include point mutation, amplification, fusion/rearrangement, and ALK fusion is more common than other types. However, the effect of different types of gene changes in molecular targeted therapy is different. Therefore, this paper introduced the relevant contents of different variants of ALK gene, focused on the research progress of targeted therapy, and proposed the future development direction.
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Humans ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase ; Molecular Targeted Therapy ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors* ; Protein Kinase Inhibitors/therapeutic use*