OBJECTIVE: To compare the efficacy and muscle injury imaging between oblique lateral lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis. METHODS: The clinical data of 60 patients with single-segment degenerative lumbar spinal stenosis who underwent surgical treatment from January 2018 to October 2019 was retrospectively analyzed. The patients were divided into OLIF groups and TLIF group according to different surgical methods. The 30 patients in the OLIF group were treated with OLIF plus posterior intermuscular screw rod internal fixation. There were 13 males and 17 females, aged from 52 to 74 years old with an average of (62.6±8.3) years old. And 30 patients in the TLIF group were treated with TLIF via the left approach. There were 14 males and 16 females, aged from 50 to 81 years old with an average of (61.7±10.4) years old. General data including operative time, intraoperative blood loss, postoperative drainage volume, and complications were recorded for both groups. Radiologic data including disc height (DH), the left psoas major muscle, multifidus muscle, longissimus muscle area, T2-weighted image hyperintensity changes and interbody fusion or nonfusion were observed. Laboratory parameters including creatine kinase (CK) values on postoperative 1st and 5th days were analyzed. Visual analogue scale(VAS) and Oswestry disability index(ODI) were used to assess clinical efficacy. RESULTS: There was no significant difference in the operative time between two groups(P>0.05). The OLIF group had significantly less intraoperative blood loss and postoperative drainage volume compared to the TLIF group(P<0.01). The OLIF group also had DH better recovery compared to the TLIF group (P<0.05). There were no significant differences in left psoas major muscle area and the hyperintensity degree before and after the operation in the OLIF group (P>0.05). Postoperativly, the area of the left multifidus muscle and longissimus muscle, as well as the mean of the left multifidus muscle and longissimus muscle in the OLIF group, were lower than those in the TLIF group (P<0.05) .On the 1st day and the 5th day after operation, CK level in the OLIF group was lower than that in the TLIF group(P<0.05). On the 3rd day after operation, the VAS of low back pain and leg pain in the OLIF group were lower than those in the TLIF group (P<0.05). There were no significant differences in the ODI of postoperative 12 months, low back and leg pain VAS at 3, 6, 12 months between the two groups(P>0.05). In the OLIF group, 1 case of left lower extremity skin temperature increased after the operation, and the sympathetic chain was considered to be injured during the operation, and 2 cases of left thigh anterior numbness occurred, which was considered to be related to psoas major muscle stretch, resulting in a complication rate of 10% (3/30). In the TLIF group, one patient had limited ankle dorsiflexion, which was related to nerve root traction, two patients had cerebrospinal fluid leakage, and the dural sac was torn during the operation, and one patient had incision fat liquefaction, which was related to paraspinal muscle dissection injury, resulting in a complication rate of 13% (4/30). All patients achieved interbody fusion without cage collapse during the 6- month follow-up. CONCLUSION Both OLIF and TLIF are effective in the treatment of single-segment degenerative lumbar spinal stenosis. However, OLIF surgery has obviously advantages, including less intraoperative blood loss, less postoperative pain, and good recovery of intervertebral space height. From the changes in laboratory indexes of CK and the comparison of the left psoas major muscle, multifidus muscle, longissimus muscle area, and high signal intensity of T2 image on imaging, it can be seen that the degree of muscle damage and interference of OLIF surgery is lower than that of TLIF.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Stenosis/surgery* ; Blood Loss, Surgical ; Lumbar Vertebrae/surgery* ; Spinal Fusion/methods* ; Treatment Outcome ; Pain, Postoperative ; Muscles ; Minimally Invasive Surgical Procedures/methods*

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.
Humans ; Atrial Fibrillation/drug therapy* ; Cardiovascular Diseases ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Atherosclerosis ; Dyslipidemias/drug therapy*

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective:The differences of chemical compositions and pharmacological activities between the core and pulp of Phyllanthi Fructus were investigated by chemical analysis and in vitro test to explore the effect of the core on the quality of this medicinal material. Method:Literature， medicinal material standards and market research on the appearance of Phyllanthi Fructus were conducted based on existing databases. Ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to identify the constituents of the core and pulp. The analysis was performed on Thermo Scientific Accucore C₁₈ column （2.1 mm×100 mm， 2.6 μm） with the mobile phase of 0.1% formic acid aqueous solution （A）-methanol （B） for gradient elution （0-25 min， 5%B； 25-30 min， 5%-95%B； 30-35 min， 95%-5%B）， the flow rate was 0.2 mL·min^-1， heating electrospray ionization （HESI） was adopted with positive and negative ion modes， and the scanning range was m/z 100-1 500. High performance liquid chromatography （HPLC） was used to determine the contents of gallic acid， corilagin， chebulagic acid and ellagic acid in the core and pulp of Phyllanthi Fructus. Analysis was performed on Welchrom C₁₈ column （4.6 mm×250 mm， 5 μm） with mobile phase of methanol （A）-0.05% phosphoric acid aqueous solution （B） for gradient elution （0-6 min， 5%A； 6-15 min， 5%-7%A； 15-20 min， 7%-15%A； 20-25 min， 15%-21%A； 25-31 min， 21%-22%A； 31-41 min， 22%A； 41-47 min， 22%-28%A； 47-51 min， 28%-32%A； 51-57 min， 32%-38%A； 57-70 min， 38%-45%A； 70-80 min， 45%-65%A； 80-85 min， 65%-5%A）， the detection wavelength was set at 270 nm. The antibacterial effects of the core and pulp of Phyllanthi Fructus on Escherichia coli and Staphylococcus aureus were investigated by filter paper method， and their antioxidant activities were compared by 1，1-diphenyl-2-picrylhydrazyl （DPPH） free radical scavenging assay. Result:A total of 47 compounds were identified in the core and pulp of Phyllanthi Fructus， mainly including tannins， flavonoids， phenolic acids， fatty acids， amino acids， organic acids， saccharides and glycosides， most of which were concentrated in the pulp， and the fatty acids in the core accounted for a higher proportion. The contents of gallic acid， corilagin， chebulagic acid， ellagic acid and other phenolic compounds in the pulp of 20 batches of Phyllanthi Fructus were much higher than those in the core. The results of antibacterial test showed that the core of Phyllanthi Fructus with different concentrations had no antimicrobial effect. The DPPH radical scavenging test showed that the antioxidant activity of the core ［half-inhibitory concentration （IC₅₀）=199.632 mg·L^-1］ was much less than that of the pulp （IC₅₀=12.688 mg·L^-1）. Conclusion:From the perspectives of polyphenol content， antibacterial and antioxidant activities， it is scientific to use Phyllanthi Fructus pulp in ancient and modern times， which may be to remove the secondary parts of Phyllanthi Fructus， so as to enhance the actual utilization rate and therapeutic effect of medicinal materials. In view of the large proportion of the core of Phyllanthi Fructus and its high content of fatty acids and other components， whether or not to use it remains to be further studied in clinical application.

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals ; Cell Cycle Proteins/genetics* ; Cell Line ; Cell Survival ; Chondroitin Sulfate Proteoglycans/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Gene Expression Regulation ; Gene Knockdown Techniques ; Infertility, Male ; Male ; Meiosis/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphate-Binding Proteins/genetics* ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics* ; Rad51 Recombinase/genetics* ; Real-Time Polymerase Chain Reaction ; Spermatocytes/metabolism* ; Spermatogenesis/genetics* ; Spermatogonia/metabolism*

Objective: To compare left ventricular myocardial mechanics detected by cardiac magnetic resonance tissue tracking(CMR-TT) between patients with constrictive pericarditis(CP) and restrictive cardiomyopathy(RCM),and see if those can be used to differentiate CP from RCM patients. Methods: A total of 23 patients with CP, 20 patients with RCM, who hospitalized in Beijing Anzhen Hospital from January 2014 to April 2019 were included in this study and 25 healthy subjects served as control group, all subjects underwent cardiac magnetic resonance examination. Myocardial mechanics were evaluated by 2-dimensional(2D) and 3-dimensional(3D) CMR-TT in terms of global longitudinal strain(GLS), circumferential strain(GCS), radial strain(GRS) and the lateral wall strain to septal wall strain ratio(lateral/septal ratio) of basal, mid-cavity and apical. The diagnostic area under the receiver operating characteristic curve (ROC) was evaluated for differentiating CP from RCM. Results: Age, sex and heart rate were similar between CP and RCM patients(all P>0.05). 2D-GLS, 3D-GLS, GCS and GRS in CP and RCM groups were significantly lower than those in normal control group(all P<0.05).3D-GLS value was significantly lower in RCM patients than in CP patients(P<0.05), the area under the curve (AUC)=0.787(sensitivity 80%, specificity 78%). 3D-GCS was significantly lower in CP group than in RCM group(P<0.05), the AUC=0.737(sensitivity 80%, specificity 65%). However, there was no significant difference between CP and RCM in 3D-GRS(P>0.05). Compared with RCM, the circumferential and radial lateral/septal ratios of the basal were significantly lower in CP group than in RCM group(both P<0.05), AUC=0.737(sensitivity 70%, specificity 83%) and 0.737 (sensitivity 60%, specificity 87%), respectively. The left ventricular myocardial mechanics strain curve of the CP,RCM and normal control were different. The CP patients presented as " rapidly down-a platform" form, the RCM presented as "slowly down" form, and normal control presented as "rapidly down" form. Conclusion: Evaluating the differences in the diastolic process of left ventricular myocardium and left ventricular myocardial mechanics strain curve is helpful to differentiate CP from RCM patients.
Cardiomyopathy, Restrictive ; Humans ; Magnetic Resonance Spectroscopy ; Myocardium ; Pericarditis, Constrictive ; Reproducibility of Results ; Ventricular Function, Left

Objective To assess the clinical use and occurrence of ad-verse reactions of Shenqifuzheng injection , and to provide reference for rational drug use in the clinic .Methods Based on the method of the real world study , the clinical data of Shenqifuzheng injection in our hos-pital was tracked and analyzed .Results A total of 438 inpatients were enrolled in this study.Shenqifuzheng injection was used accorded with the drug instruction mostly . The incidence of adverse drug reaction ( ADR ) of Shenqifuzheng injection was 0.23%, which showed good safety.Conclusion The application of Shenqifuzheng injection was rational and safe in our hospital .The real world study is effective for clinical reasearch of medicine .

The combined use of batifiban, a synthetic platelet GPII b/ IIIa receptor antagonist, and antithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggregation (%) suggested that neither batifiban alone nor antithrombin agents alone could provide such potent inhibition rate (>80%) to obtain the best clinical efficacy, but they had a synergistic effect on platelet inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.
Administration, Oral ; Adolescent ; Adult ; Area Under Curve ; Aspirin ; administration & dosage ; pharmacology ; China ; Drug Administration Schedule ; Female ; Fibrinolytic Agents ; administration & dosage ; pharmacology ; Heparin ; administration & dosage ; pharmacology ; Humans ; Infusions, Intravenous ; Injections, Intravenous ; Male ; Metabolic Clearance Rate ; drug effects ; Peptides, Cyclic ; administration & dosage ; pharmacokinetics ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacokinetics ; Ticlopidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Time Factors ; Young Adult