Study on quality standard for vinegar-steamed Corydalis rhizoma / 药学实践杂志

Objective To set up the quality standards for vinegar-steamed Corydalis rhizome, which can be used for the quality control of production, supervision, circulation and application of the steam processed Corydalis rhizoma with vinegar. Methods The moisture content, total ash, ethanol extract content and active ingredients of the steam processed Corydalis rhizoma with vinegar were determined according to the related assay method in Part IV of Chinese Pharmacopeia 2015. Results According to the guidelines from the traditional Chinese medicine quality standards and related testing methods, the moisture content of steam processed Corydalis rhizoma with vinegar should be less than 15.0%, the total ash content less than 4.0%, the ethanol extract content more than 11.0%, and the representative component of tetrahydropalmatine more than 0.05%. Conclusion The established process with this study for the quality standard of vinegar-steamed Corydalis rhizoma was conformed to the state requirements for traditional Chinese medicine. It can be used as a reference for the quality standard of vinegar-steamed Corydalis rhizoma.

FDA Premarket Pathways for Combination Products / 中国医疗器械杂志

Combination products face unique R&D, manufacturing, clinical, and regulatory challenges compared to individual devices, drugs, or biological products. Based on the interpretation of the relevant policies and the latest principles of combination products, this paper expounds the FDA's guidance, application trends, and application strategies for the pre-market pathways of combination products, with a view to providing relevant information for Chinese researchers and manufacturers when they start to entry the United States market.

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3+CD25+CD4+ Treg cells via the IL-2/STAT5 signaling pathway / 中国天然药物

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.

The Effect of Doxycycline on the Expression of MMP-2 and MMP-9 in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in multiple myeloma (MM) patients, and analyze the effect of doxycycline (DOX) on the expression of MMP-2 and MMP-9 in MM cells.@*METHODS@#The peripheral blood and bone marrow samples of MM patients were collected, and the patients were divided into three groups: newly diagnosed group, remission group and relapsed/refractory group, while the peripheral blood samples of 34 health people and the bone marrow samples of 17 IDA patients were selected as normal control and control group. The levels of MMP-2 and MMP-9 were detected by ELISA. The protein levels of MMP-2 and MMP-9 in H929 cells treated by different concentrations of DOX were analyzed by Western blot. After H929 cells was treated by Akt inhibitor MK-2206 2HCl in combination with DOX, Western blot was used to detect the levels of MMP-2 and MMP-9.@*RESULTS@#The levels of MMP-2 and MMP-9 in newly diagnosed MM patients were higher than those in control (P<0.05), while for the patients in the remission group were decreased, but still higher than those in control. The levels of MMP-2 and MMP-9 were increased again for the patients in relapsed/refractory group, and showed no significant difference as compared with those in newly diagnosed group. The levels of MMP-2 and MMP-9 could be inhibited by 10 mg/L and 15 mg/L DOX treated by H929 cell. The protein levels of MMP-2 and MMP-9 showed no altered in H929 cells treated by 5 nmol/L MK-2206 2HCl alone. DOX exerted more profound inhibitory effect to MMP-2 and MMP-9 expression in H929 cells when Akt inhibitor MK-2206 2HCl was combined with DOX.@*CONCLUSION@#The levels of MMP-2 and MMP-9 are increased in MM patients and related to the disease status of MM. DOX can inhibit the expression of MMP-2 and MMP-9 in MM cells, and antagonizing its activation of Akt signaling pathway can further enhance the inhibitory effect.

Effect of Doxycycline on Intrinsic Apoptosis of Myeloma Cell Line H929 and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.@*METHODS@#Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.@*RESULTS@#DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05).@*CONCLUSION@#DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.

Clinical assessment of moderate-dose glucocorticoid in the treatment of recurrence of primary nephrotic syndrome in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS).@*METHODS@#A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions.@*RESULTS@#There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018).@*CONCLUSIONS@#For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Effect of wheat-grain moxibustion on the expression of Beclin-1/GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR.@*METHODS@#A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope.@*RESULTS@#After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups.@*CONCLUSION@#Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.

Preparation and characterization of linolenic acid-chitosan micelle for doxorubicin oral delivery and its in situ intestinal absorption in rats / 药学学报

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome / 中华烧伤杂志

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research / 中华心血管病杂志

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.

Expression and significance of serum soluble T cell immunoglobulin-domain and mucin-domain protein-3 and galectin-9 in patients with early acute pancreatitis / 中华消化杂志

Objective:To investigate the expression and significance of serum soluble T cell immunoglobulin-domain and mucin-domain protein-3 (sTIM-3) and galectin-9 (Gal-9) in patients with early acute pancreatitis (AP), so as to provide theoretical and clinical evidence for the early prediction and diagnosis of AP.Methods:From 15 September 2020 to 23 July 2021, a total of 94 AP patients with a time from onset to admission ≤48 h who were admitted to Changzhou No.2 People′s Hospital, Nanjing Medical University were selected, including 42 cases of mild acute pancreatitis (MAP), 35 cases of moderately severe acute pancreatitis (MSAP) and 17 cases of severe acute pancreatitis (SAP). The basic clinical features of AP patients were collected. Acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ), modified computed tomography severity index (MCTSI) and bedside index for severity in acute pancreatitis (BISAP) scores were evaluated in all AP patients. The levels of serum interleukin (IL)-6, IL-10, Gal-9 and sTIM-3 were detected with enzyme linked immunosorbent assay. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis. Spearman rank correlation test and Pearson correlation analysis were used to analyze the correlation of sTIM-3, Gal-9 with inflammatory indicators and AP related scoring systems. Receiver operating characteristic curve (ROC) was performed for efficiency analysis of the combination of sTIM-3 and Gal-9 in predicting the severity of AP patients. Results:Serum sTIM-3, Gal-9 and IL-6 levels of SAP patients were higher than those of MAP patients (2 085.00 ng/L (1 628.00 ng/L, 2 673.00 ng/L) vs. 746.10 ng/L (514.50 ng/L, 1 303.00 ng/L); 466.60 ng/L (375.90 ng/L, 629.30 ng/L) vs. 108.10 ng/L (90.29 ng/L, 138.90 ng/L); (323.60±62.93) ng/L vs. (42.90±28.82) ng/L), while IL-10 level was lower than that of MAP patients ((760.30±200.40) ng/L vs. (1 206.00±566.30) ng/L), and the differences were statistically significant ( Z=45.00 and <0.01, t=23.62 and 3.15; all P<0.01). The APACHE Ⅱ and BISAP scores of SAP patients were higher than those of MAP and MSAP patients (12.00(6.00, 16.50) vs. 3.00(2.00, 5.00) and 6.00(3.00, 8.00); 3.00(3.00, 4.00) vs.1.00(1.00, 1.00) and 2.00(2.00, 3.00)), and the MCTSI score was higher than that of MAP patients (4.00(3.00, 6.00) vs. 2.00(0.00, 2.00)), and the differences were statistically significant ( Z=644.50, 704.00, 474.50, 492.50 and 664.00, all P<0.001). Serum sTIM-3 and Gal-9 were positively correlated with the pro-inflammatory factor IL-6 ( r=0.552 and 0.297, P<0.001 and =0.004). Serum sTIM-3 was negatively correlated with the anti-inflammatory factor IL-10 ( r=-0.397, P<0.001). There was no correlation between Gal-9 and the anti-inflammatory factor IL-10 ( P>0.05). Serum sTIM-3 and Gal-9 were positively correlated with APACHE Ⅱ, MCTSI and BISAP scores ( r=0.210, 0.271 and 0.363, P=0.042, =0.008 and <0.001; r=0.390, 0.448 and 0.440, all P<0.001). The areas under ROC curves (95% confidence interval) of serum sTIM-3 and Gal-9 detected alone and in combination was 0.805 (0.716 to 0.895), 0.814 (0.725 to 0.903) and 0.856 (0.773 to 0.939), respectively, and the sensitivity was 69.2%, 67.3%, 75.0%, respectively, and the specificity was 83.3%, 97.6%, 97.6%, respectively. Conclusions:The serum levels of sTIM-3 and Gal-9 increased in patients with early AP and are correlated with the severity of AP. The combined detection of sTIM-3 and Gal-9 has high sensitivity in predicting early AP, and the two indicators may be the reliable predictors of early AP.

Synthesis, bioactivity evaluation of dibenzoyl methane halophenols and their interactions with CAV-1 / 药学学报

Caveolin-1 (CAV-1) is related to inflammation, oxidative damage, and immunity. In order to obtain a series of dibenzoylmethane halophenols with strong anti-inflammatory and antioxidant effects targeting CAV-1, twenty-nine target compounds were therefore synthesized by Baker-Ventaraman rearrangement and demethylation reaction, starting from the substituted benzoyl chloride and o-hydroxyacetophenone, and their interactions with CAV-1 were investigated by BLI technique. Their in vitro anti-inflammatory and antioxidant properties were also evaluated. The results showed that compounds A6, A17, A18, and A29 not only specifically bind to CAV-1, but also present strong anti-inflammatory and antioxidant effects. These results suggest that this class of compounds can affect the signaling pathways related to inflammation and oxidative stress by directly acting on CAV-1. In particular, these compounds exhibit the most significantly inhibitory effects on IL-1β and COX-2 release. IL-1β plays a key regulatory role in the development of arthritis. Therefore, it is worth expecting for the application of such compounds in the prevention and treatment of arthritis.

Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation / 中国实验方剂学杂志

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （<italic>P</italic><0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （<italic>P</italic><0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （<italic>P</italic><0.01）， and scores of three symptom dimensions were lower than those in control group （<italic>P</italic><0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （<italic>P</italic><0.01）， and CD8⁺ was lower than those in the control group （<italic>P</italic><0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-<italic>β</italic>₁ were lower than those in the control group （<italic>P</italic><0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （<italic>χ</italic>²=4.572， <italic>P</italic><0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Observation on clinical effect of acupuncture combined with wheat-grain moxibustion for mild to moderate postpartum depression / 中国针灸

OBJECTIVE@#To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression.@*METHODS@#Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed.@*RESULTS@#After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (@*CONCLUSION@#Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.

Early efficacy of direct anterior approach versus posterolateral approach for total hip arthroplasty in elderly patients / 中华老年医学杂志

Objective:To compare the early efficacy of direct anterior approach versus posterolateral approach for total hip arthroplasty in elderly patients.Methods:The 48 elderly patients receiving total hip arthroplasty from September 2017 to September 2019 were divided into two groups: DAA group(n=23, 30 hips)receiving direct anterior approach for total hip arthroplasty, and PLA group(n=25, 33 hips)receiving posterolateral approach for total hip arthroplasty in this retrospective study.The operation time, blood loss, length of hospital stay, acetabular abduction angle, anteversion angle, and intraoperative and postoperative complications were recorded and compared between the two groups.The hip function was compared with Visual Analogue Scale(VAS)and Harris Hip Score(HHS).Results:All the 48 patients were followed up for 7-31 months, with an average of 22.8 months in DAA group, and 24 months in PLA group.The operation time was less in PLA group than in DAA group[(49.3±5.7)min vs.(70.3±6.2)min, t=12.22, P=0.00], while the hospital stay was longer in PLA group than in DAA group, with a statistically significant difference[(7.8±1.5)d vs.(5.6±1.3)d, t=-5.40, P=0.00]. There was no significant difference in intraoperative blood loss between the two groups[(173.1±47.9)ml vs.(189.6±48.7)ml, t=1.18, P=0.24]. The VAS and HHS scores were better at 1 month after operation and at the last follow-up than before operation in both DAA and PLA group(all P<0.05). The VAS and HHS scores were better in DAA than in PLA groups( P<0.05)at 1 month after surgery.However, at the last follow-up, there was no significant difference in VAS and HHS scores between the two groups( P>0.05). Conclusions:The early results of direct anterior approach for total hip arthroplasty are satisfactory in patients aged 85 years and older.It has the advantages of less trauma, faster postoperative recovery and shorter hospital stay.

Effect of different femoral tunnel locations on patellofemoral joint during single-bundle anterior cruciate ligament reconstruction / 中国组织工程研究

BACKGROUND: Studies have shown that arthroscopic single-bundle anterior cruciate ligament reconstruction can restore the forward stability of the knee joint, but the rotational stability of the knee joint and the matching degree with the patellofemoral joint are affected by the central position of the femoral and tibial tunnels. OBJECTIVE: To investigate the relationship between the location of different femoral tunnel centers and patellofemoral articulation and cartilage conditions in young and middle-aged patients with anterior cruciate ligament reconstruction, and to carry out the correlation analysis of patient study factors to further explore the location of the femoral tunnel with the least influence on the patellofemoral joint. METHODS: Seventy patients with anterior cruciate ligament rupture were diagnosed by preoperative MRI, physical examination and intraoperative arthroscopy. All patients were divided into quasi-isometric group and quasi-anatomical group according to the parity of random numbers. In the quasi-isometric group, a Kirschner needle was inserted 7 mm distal to the apex of the lateral wall of the intervertebral fossa using a femoral locator. In the quasi-anatomical group, the Kirschner needle was inserted at the lateral wall of the intercondylar fossa and at the foot print center of the original anterior cruciate ligament. The central coordinates of the femoral tunnel were evaluated on the near-far-front-rear plane based on a standardized grid system, while the central coordinates of the tibial tunnel was evaluated on the anterior-posterior-inner-outer plane, labeled as quadrant Y% and quadrant X%. By comparing the baseline data of patients in the two groups, the difference of lateral patellofemoral angle (LPFA), the difference of cartilage quantitative T2 value, and the correlation between various research factors, the surgical operators were further guided to carry out clinical practice. The implementation of the study protocol complied with the relevant ethical requirements of the First Affiliated Hospital of Anhui Medical University, and all patients signed an informed consent form prior to the participation in the trial. RESULTS AND CONCLUSION: There was no significant difference in baseline data between the two groups, but a significant difference in LPFA existed between the two groups, (0.57±0.33)° in the quasi-anatomical group vs. (1.55±0.36)° in the quasi-isometric group (P<0.001). The T2 values of medial patella, lateral patella and trochlear cartilage in the quasi-anatomical group were all smaller than the corresponding values of the quasi-isometric group. Quadrant X% had a significant negative correlation with LPFA difference (R=-0.664, P<0.01). Quadrant Y% was positively correlated with LPFA difference (R=0.804, P<0.01). The difference of LPFA was significantly positively correlated with T2 values of trochlear and patellar outer cartilage (R=0.651, 0.655, P<0.01). T2 values of trochlea and lateral patella cartilage were negatively correlated with postoperative Lysholm score (R=-0.505, -0.529, P<0.01). Quadrant Y% was highly correlated with T2 value of lateral patella (R=0.825, P<0.01), and significantly correlated with T2 value of trochlear cartilage (R=0.798, P<0.01). Quadrant X% was negatively correlated with T2 values of lateral patella and pulley cartilage (R=-0.639, -0.657, P<0.01). By exploring the change of the patellofemoral joint at early stage after single-bundle anterior cruciate ligament reconstruction, we found that the quasi-anatomical reconstruction relative to the quasi-isometric reconstruction requires less patellofemoral articular cartilage degeneration and smaller patellar tilt angle. Therefore, the surgeon is required to local the center point of the femoral tunnel as far as possible at the quasi-anatomical position, thereby minimizing the degeneration of the patellofemoral joint.

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection / 医学前沿

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Surgical treatment of traumatic osteomyelitis of extremities with MRSA infection / 中国骨伤

OBJECTIVE@#To summarize and discuss the clinical efficacy and application value of intravenous drip of linezolid combined with local targeted sustained-release of vancomycin in the treatment of traumatic osteomyelitis of extremities infected with MRSA.@*METHODS@#Thirty patients with traumatic osteomyelitis of extremities infected by MRSA from March 2015 to March 2017 were analyzed retrospectively, including 21 males and 9 females; aged 25 to 64 years old, with an average age of(47.94± 6.23) years old;the course of disease ranged from 9 to 23 months, with an average of (15.68±6.23) months. The lesions were located in tibia in 18 cases and calcaneus in 12 cases. The causes of injury were fall injury in 12 cases, trafficaccident injury in 9 cases and fall injury in 9 cases. There were 22 patients with closed fractures and 8 patients with open fractures. There were 13 cases of internal fixation. Twenty-two patients had sinustract, 8 patients had soft tissue defect with bone and internal fixation exposure, soft tissue defect area ranged from 2.0 cm × 3.0 cm to 8.2 cm × 12.3 cm;10 patients had bone defect, defect area ranged from 0.5 to 3.4 cm;bacterial culture of sinus tract or wound secretion in all patients was MRSA. On the basis of thorough debridement, calcium sulfate artificial bone loaded with vancomycin was implanted in the lesion, and linezolid and glucose injection was given intravenously during the perioperative period. The patients were followed up regularly according to the time of antibiotic use, blood routine, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, liver and kidney function and other related laboratory indexes, X-ray, CT and other imaging examinations, bone healing, flap survival, joint function and McKee's osteomyelitis cure criteria.@*RESULTS@#All the patients were followed up, and the duration ranged from 3 to 6 years, with a mean of (4.23±0.76) years. No recurrence of osteomyelitis occurred. Fracture healing, infection control, wound healing and functional recovery were achieved.@*CONCLUSION@#Intravenous drip of linezolid combined with local targeted sustained-release of vancomycin for the treatment of MRSA infected traumatic osteomyelitis in limbs have significant effects and low recurrence rates.

Psychosis speech recognition algorithm based on deep embedded sparse stacked autoencoder and manifold ensemble / 生物医学工程学杂志

Speech feature learning is the core and key of speech recognition method for mental illness. Deep feature learning can automatically extract speech features, but it is limited by the problem of small samples. Traditional feature extraction (original features) can avoid the impact of small samples, but it relies heavily on experience and is poorly adaptive. To solve this problem, this paper proposes a deep embedded hybrid feature sparse stack autoencoder manifold ensemble algorithm. Firstly, based on the prior knowledge, the psychotic speech features are extracted, and the original features are constructed. Secondly, the original features are embedded in the sparse stack autoencoder (deep network), and the output of the hidden layer is filtered to enhance the complementarity between the deep features and the original features. Third, the L1 regularization feature selection mechanism is designed to compress the dimensions of the mixed feature set composed of deep features and original features. Finally, a weighted local preserving projection algorithm and an ensemble learning mechanism are designed, and a manifold projection classifier ensemble model is constructed, which further improves the classification stability of feature fusion under small samples. In addition, this paper designs a medium-to-large-scale psychotic speech collection program for the first time, collects and constructs a large-scale Chinese psychotic speech database for the verification of psychotic speech recognition algorithms. The experimental results show that the main innovation of the algorithm is effective, and the classification accuracy is better than other representative algorithms, and the maximum improvement is 3.3%. In conclusion, this paper proposes a new method of psychotic speech recognition based on embedded mixed sparse stack autoencoder and manifold ensemble, which effectively improves the recognition rate of psychotic speech.