Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Osteoarthritis （OA） is characterized by articular cartilage degeneration， synovial hyperplasia， hyperosteogeny， and narrowing of joint space， which can be caused by trauma， inflammation， and other factors. With the increasing global population aging， the incidence of OA is rising year by year， making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex， including oxidative stress， autophagy， and apoptosis. Recent studies have found that ferroptosis， a new type of cell death， is also an important pathogenic factor in OA， characterized by a series of complex changes such as iron ion accumulation， glutathione （GSH） depletion， and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation， delay extracellular matrix （ECM） degradation， and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement， but there are limitations. Traditional Chinese medicine （TCM） has been widely used in the treatment of various diseases because of its low cost， low drug resistance， and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets， multiple levels， and aspects， but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism， lipid peroxidation， cysteine/glutamate transporter system Xc^- （system Xc^-）/GSH/glutathione peroxidase 4 （GPX4） pathway， nicotinamide adenine dinucleotide phosphate（NADPH）/ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀） pathway， tumor protein p53 in OA， and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.

Objective To study the relationship between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain in patients with hip osteoarthritis after hip arthroplasty.Methods The clinical data of 30 patients with facet joint-derived low back pain induced by hip osteoarthritis who underwent unilateral hip arthroplasty(observation group)from June 2019 to November 2020 in our hospital were retrospectively analyzed,and 50 healthy subjects who underwent lumbar X-ray examination in the physical examination center of our hospital at the same time were randomly selected as the control group.The sagittal spinopelvic parameters were measured based on the X-ray,including pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),sacrum pubic incidence(SPI)and sacrum pubic posterior angle(SPPA).The correlation between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain was analyzed by multiple linear regression,and its diagnostic efficacy to facet joint-derived low back pain was analyzed by receiver operating characteristic(ROC)curve.Results The PI,LL,SPI or SPA before and 1 year after surgery of the observation group had no significant difference combined with those of the control group(P>0.05).The PT before surgery of the observation group was smaller than that of the control group(P<0.05),and the SS before surgery was larger than that of the control group(P<0.05).Multiple linear regression analysis showed that PT and SS before surgery were correlated with facet joint-derived low back pain(P<0.05).The sensitivity of PT and SS before surgery in diagnosing facet joint-derived low back pain were 50.00%and 73.30%,with the specificity of 88.00%and 78.00%,respectively.ROC curve analysis showed that the area under the curve of PT and SS before surgery in diagnosing facet joint-derived low back pain were 0.708(95%CI:0.595 to 0.822)and 0.775(95%CI:0.673 to 0.877),respectively.Conclusion Patients with hip osteoarthritis pain have significantly larger SS and significantly smaller PT.Hip arthroplasty can alleviate the symptoms of low back pain without affecting the sagittal spinopelvic balance;the PT and SS before surgery are correlated with the facet joint-derived low back pain,and they are of high value in the diagnosing facet joint-derived low back pain.

For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

Skeletal muscle wasting refers to a loss of skeletal muscle mass and function.Mitochondrial quality control(MQC)is the basis by which normal physiological mitochondrial function is maintained and mainly involves the regulation of mitochondrial biogenesis,mitochondrial dynamics(fission/fusion),and mitophagy.MQC maintains muscle homeostasis by regulating the relative stability of mitochondrial shape,quantity,and quality.As an economical and effective treatment for muscular atrophy,exercise interventions are widely used,but the relationship between exercise intervention and MQC is not clear.This paper discusses the role of mitochondrial biogenesis,mitochondrial dynamics,and mitophagy in skeletal muscle atrophy and related molecular targets.We thoroughly analyze the mechanisms by which MQC-mediated exercise can improve the skeletal muscle atrophy caused by aging,disuse,and cancer cachexia in order to provide theoretical guidance for intervention.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L^-1.

Objective To compare the clinical effects of three treatment methods including systemic thrombolysis(ST),catheter-directed thrombolysis(CDT),and AngioJet percutaneous mechanical thrombectomy(PMT)in acute lower extremity deep venous thrombosis(LEDVT). Methods The data of 82 patients diagnosed with LEDVT in the Department of Vascular and Gland Surgery of the First Affiliated Hospital of Hebei North University from January 2017 to December 2020 were collected.The patients were assigned into a ST group(n=50),a CDT group(n=16),and a PMT group(n=16)according to different treatment methods.The efficacy and safety were compared among the three groups. Results Compared with that before treatment,the circumferential diameter difference of both lower limbs on days 1,2,and 3 of treatment in the ST,CDT,and PMT groups reduced(all P<0.001).The PMT group showed smaller circumferential diameter difference of lower limbs on days 1,2,and 3 of treatment than the ST group(all P<0.001)and smaller circumferential diameter difference of the lower patellar margin on day 1 of treatment than the CDT group(P<0.001).The PMT group showed higher diminution rate for swelling of the affected limb at the upper and lower edges of the patella than the ST group(P<0.001)and higher diminution rate for swelling at the upper edge of the patella than the CDT group(P=0.026).The incidence of complications after treatment showed no significant differences among the three groups(all P>0.05).The median of hospital stay in the PMT group was shorter than that in the ST and CDT groups(P=0.002,P=0.001).The PMT group had higher thrombus clearance rate than the ST group(P=0.002)and no significant difference in the thrombus clearance rate from the CDT group(P=0.361).The vascular recanalization rates in the PMT(all P<0.001)and CDT(P<0.001,P=0.002,P=0.009)groups 3,6,and 12 months after treatment were higher than those in ST group,and there were no significant differences between PMT and CDT groups(P=0.341,P=0.210,P=0.341). Conclusions ST,CDT,and PMT demonstrated significant efficacy in the treatment of LEDVT,and PMT was superior to ST and CDT in terms of circumferential diameter difference of the lower limbs,diminution rate for swelling of the affected limb,thrombus clearance rate,length of hospital stay,and long-term vascular recanalization.There was no obvious difference in safety among the three therapies.
Humans ; Thrombolytic Therapy/methods* ; Fibrinolytic Agents/therapeutic use* ; Treatment Outcome ; Thrombectomy/methods* ; Venous Thrombosis/drug therapy* ; Lower Extremity/blood supply* ; Catheters ; Retrospective Studies

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.