Research progress in the route of administration and corresponding dosage form of triamcinolone acetonide / 中国药房

As a glucocorticoid drug with wide clinical application， triamcinolone acetonide can be administered by multiple routes， such as eye， nose， joint cavity， and skin， for the treatment of various local diseases such as arthritis， macular edema， rhinitis， and urticaria. As a drug with extremely low solubility in water， the dose form of triamcinolone acetonide is closely correlated with administration route and site. The dosage form of triamcinolone acetonide administered via injection（including joint cavity injection， vitreous injection， suprachoroidal injection， intramuscular injection） is mainly suspension， and the representative drugs include Kenalog-40®， Zilretta®， Triesence®， Xipere®， etc.； the dosage forms of nasal mucosal administration are mostly sprays， and the representative drug is Nasacort®； the dosage forms of oral mucosal administration are mostly patches， ointments and creams， and the representative drug is Oracort®； the dosage forms for transdermal administration are mostly ointments， creams and lotions， and the representative drugs include Trianex®， Teva-Triacomb®， etc. At present， the research on dosage forms of triamcinolone acetonide by various administration routes mainly focuses on the construction of delivery carriers， the addition of cosolvents or the use of new delivery tools.

Clinical characteristics and survival comparison between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with cervical cancer / 肿瘤研究与临床

Objective:To summarize the clinical features and survival differences between human immunodeficiency virus (HIV)-positive and HIV-negative cervical cancer patients, and to explore the factors influencing the prognosis.Methods:The clinical data of patients with cervical cancer diagnosed and treated in Zhongnan Hospital of Wuhan University from January 2015 to January 2022 were retrospectively analyzed. There were 46 HIV-positive cases and 587 HIV-negative cases; all 46 HIV-positive patients had squamous cell carcinoma, while 504 HIV-negative patients had squamous cell carcinoma. According to age and clinical staging, 230 HIV-negative squamous cell carcinoma patients were screened to match with 46 HIV-positive squamous cell carcinoma patients according to 1∶5. The clinical features of HIV-positive and HIV-negative patients were compared in all matched patients with pathological type of squamous cell carcinoma; the Kaplan-Meire method was used to analyze the overall survival (OS) and the comparison of OS was made by using log-rank test. Multivariate Cox proportional risk model was used to analyze the independent factors affecting the OS of patients with cervical squamous cell carcinoma.Results:The differences in the age, pathological types, clinical staging between 46 HIV-positive patients and 587 HIV-negative patients were statistically significant (all P < 0.05). There were statistically significant differences in age and clinical staging between 46 HIV-positive squamous cell carcinoma patients and 504 HIV-negative squamous cell carcinoma patients (all P < 0.05). After 1∶5 matching, there were no statistically significant differences in the age, clinical staging between 46 patients with HIV-positive squamous cell carcinoma and 230 patients with HIV-negative squamous cell carcinoma. The OS of HIV-positive patients in the entire group,pathological type of squamous cell carcinoma or after pairing was worse than that of HIV-negative patients (all P < 0.001). The median OS time of HIV-positive patients was 63 months (95% CI 61-109 months), while the median OS time of HIV-negative patients was not reached (95% CI 165-178 months, 164-178 months, 143-173 months, respectively). Multivariate Cox regression analysis showed that clinical staging Ⅲ-Ⅳ was an independent risk factor for OS in patients with cervical squamous cell carcinoma (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ: HR = 1.573, 95% CI 1.032-2.397, P = 0.035); HIV infection was an independent protective factor for OS (HIV-positive vs. HIV-negative: HR = 0.087, 95% CI 0.042-0.182, P < 0.001), indicating that HIV-positive patients had an advantage in OS compared to HIV-negative patients at the same age and clinical staging. Age was not an independent influencing factor for OS ( P > 0.05). Conclusions:The onset age of HIV-positive cervical cancer tends to be younger and the clinical staging is late when patients are diagnosed. HIV-positive patients have poor prognosis.

Analysis of the cost of hospital delivery for postpartum women in large public hospitals in Beijing / 中华医院管理杂志

Objective:To analyze the hospitalization costs of delivery for postpartum women with different delivery methods, ages and comorbidities or complications, for references for medical institutions and medical insurance management departments to develop payment and compensation standards for inpatient delivery.Methods:The first page of medical records of hospitalized delivery women admitted to 8 large tertiary hospitals in Beijing from January 2018 to December 2021 were selected. Descriptive analysis was made on the mode of delivery, age, hospitalization expenses and cost structure of puerpera, as well as the hospitalization expenses of puerpera with different complications or complications. Wilcoxon rank sum test, Kruskal-Wallis H test, and Chi-squared test were used to statistically compare the level and structure differences between groups. Results:A total of 23 320 pregnant women were included, with an average age of 32.3 years. There were 13 605 cases of natural delivery and 9 715 cases of caesarean section. The median cesarean section rate in the right age group (<35 years old) and the elderly group (35-50 years old) were 36.73% and 56.58%, respectively, and the median hospital expenses were 5 865 yuan and 7 042 yuan, respectively. The median hospital expenses for natural delivery and caesarean section were 4 452 yuan and 10 033 yuan, respectively. The highest proportion of hospitalization expenses for natural delivery and cesarean section were treatment expenses (23.45%) and medicine expenses (29.19%), respectively. The median of hospitalization cost for women with≥2 comorbidities or complications (6 736 yuan) was higher than that for women with 1 comorbidities or complications (5 794 yuan).Conclusions:The hospitalization cost of cesarean section was significantly higher than that of natural delivery and the rate of cesarean section and the cost of delivery in women aged 35 and above were higher than those under 35 years old. The structure of hospitalization cost was different in different delivery modes, and the complications or complications had a greater impact on the average hospitalization expenses.

Changes in CD100 expression and its regulatory effect on CD8 + T cell function in peripheral blood of patients with herpes zoster / 中华皮肤科杂志

Objective:To investigate changes in expression of plasma soluble CD100 (sCD100) and membrane-bound CD100 (mCD100) on peripheral T cells in patients with herpes zoster, and to observe the regulatory effect of exogenous CD100 on CD8 + T cells. Methods:A total of 53 patients with herpes zoster attending the Zhumadian Central Hospital from July 2019 to April 2021 were enrolled, so were 25 age- and sex-matched healthy controls. Anticoagulated venous blood samples were collected, plasma and peripheral blood mononuclear cells were isolated, plasma sCD100 levels were detected by enzyme-linked immunosorbent assay, and mCD100 expression on CD4 + and CD8 + T cells was determined by flow cytometry. After the purification of CD8 + T cells, the secretion levels of cytotoxic molecules and cytokines by CD8 + T cells were measured and compared between herpes zoster patients and controls. Some purified CD8 + T cells from herpes zoster patients were stimulated with recombinant human CD100 and recombinant varicella-zoster virus glycoprotein, and the effect of recombinant human CD100 on the secretion of cytotoxic molecules and cytokines by CD8 + T cells was investigated. Comparisons between groups were conducted by t test. Results:Plasma sCD100 levels were significantly lower in the herpes zoster group (1.12 ± 0.23 ng/ml) than in the control group (1.31 ± 0.28 ng/ml, t = 2.97, P = 0.004), the proportion of mCD100 + CD8 + T cells was significantly higher in the herpes zoster group (17.41% ± 4.26%) than in the control group (14.69% ± 3.70%, t = 2.52, P = 0.014), and no significant difference in the proportion of mCD100 + CD4 + T cells was found between the two groups (2.52% ± 0.58% vs. 2.32% ± 0.56%, t = 1.27, P = 0.208). The herpes zoster group showed significantly decreased mRNA expression of perforin and granzyme B in, and lower secretion levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α by CD8 + T cells compared with the control group (all P < 0.05). After stimulation with recombinant human CD100, levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α in the culture supernatant of CD8 + T cells (43.68 ± 14.12, 126.8 ± 22.92, 12.79 ± 3.66, 310.0 ± 79.90 pg/ml, respectively ) were significantly higher than those in non-stimulated group (34.55 ± 10.78, 99.04 ± 10.44, 9.53 ± 2.00, 275.6 ± 68.04 pg/ml, respectively, all P < 0.05) . Conclusion:There was an imbalance between sCD100 and mCD100 expression in patients with herpes zoster, and exogenous sCD100 may enhance the cytotoxicity of CD8 + T cells in herpes zoster patients.

Analgesic effect of buccal acupuncture on patients after lumbar spinal fusion: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of buccal acupuncture on pain after lumbar spinal fusion.@*METHODS@#Sixty patients undergoing lumbar spinal fusion were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case was eliminated). The patients in the control group were treated with routine anesthesia. On the basis of the control group, the patients in the observation group were treated with buccal acupuncture at bilateral back point, waist point, and sacral point for 30 min per treatment. The first acupuncture was given before anesthesia induction, and then once a day postoperation for two days, totally 3 treatments. The dosage of sufentanil, the number of remedial analgesia, and the incidence of nausea and vomiting within 48 h after surgery were compared between the two groups; rest and motion visual analogue scale (VAS) scores at 2 (T1), 8 (T2), 12 (T3), 24 (T4), and 48 (T5) h after surgery were observed; the quality of recovery-15 scale (QoR-15) at 24 and 48 h after surgery were evaluated.@*RESULTS@#The dosage of sufentanil and the number of remedial analgesia within 48 h after surgery in the observation group were lower than those in the control group (P<0.01). There was no significant statistically difference in rest and motion VAS scores between the two groups in T1, T2, T3, T4 and T5 (P>0.05). The QoR-15 scores in the observation group at 24 and 48 h after surgery were higher than those in the control group (P<0.01). The incidence of nausea in the observation group was lower than that in the control group (P<0.05).@*CONCLUSION@#Buccal acupuncture could reduce the amount of postoperative analgesic drugs of patients after lumbar spinal fusion, and promote early postoperative recovery.

Research progress of artificial intelligence in 3D printed drugs / 药学学报

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

T cell immunotherapy mediated by dual-affinity aptamer targeted liposome / 药学学报

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Correlation between pelvic relapses of rectal cancer after radical and R0 resection: A regression model-based analysis / 中华胃肠外科杂志

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.

Laparoscopic versus open pelvic exenteration for locally advanced rectal cancer: analysis of short- and long-term effects / 中华胃肠外科杂志

Objective: To explore the feasibility, safety, and short- and long-term efficacy of laparoscopic pelvic exenteration (LPE) in treating locally advanced rectal cancer. Methods: The clinical data of 173 patients who had undergone pelvic exenteration (PE) for locally advanced rectal cancer that had been shown by preoperative imaging or intraoperative exploration to have invaded beyond the mesorectal excision plane and adjacent organs in the Cancer Hospital, Chinese Academy of Medical Sciences (n=64) and Peking University First Hospital (n=109) from 2010 January to 2021 December were collected retrospectively. Laparoscopic PE (LPE) had been performed on 82 of these patients and open PE (OPE) on 91. Short- and long-term outcomes (1-, 3-, and 5-year overall and disease-free survival and 1- and 3-year cumulative local recurrence rates) were compared between these groups. Results: The only statistically significant difference in baseline data between the two groups (P>0.05) was administration of neoadjuvant therapy. Compared with OPE, LPE had a significantly shorter operative time (319.3±129.3 minutes versus 417.3±155.0 minutes, t=4.531, P<0.001) and less intraoperative blood loss (175 [20-2000] ml vs. 500 [20-4500] ml, U=2206.500, P<0.001). The R0 resection rates were 98.8% and 94.5%, respectively (χ2=2.355, P=0.214). At 18.3% (15/82), and the incidence of perioperative complications was lower in the LPE group than in the OPE group (37.4% [34/91], χ2=7.727, P=0.005). The rates of surgical site infection were 7.3% (6/82) and 23.1% (21/91) in the LPE and OPE group, respectively (χ2=8.134, P=0.004). The rates of abdominal wound infection were 0 and 12.1% (11/91) (χ2=10.585, P=0.001), respectively, and of urinary tract infection 0 and 6.6% (6/91) (χ2=5.601, P=0.030), respectively. Postoperative hospital stay was shorter in the LPE than OPE group (12 [4-60] days vs. 15 [7-87] days, U=2498.000, P<0.001). The median follow-up time was 40 (2-88) months in the LPE group and 59 (1-130) months in the OPE group. The 1-, 3-, and 5-year overall survival rates were 91.3%, 76.0%, and 62.5%, respectively, in the LPE group, and 91.2%, 68.9%, and 57.6%, respectively, in the OPE group. The 1, 3, and 5-year disease-free survival rates were 82.8%, 64.9%, and 59.7%, respectively, in the LPE group and 76.9%, 57.8%, and 52.7%, respectively, in the OPE group. The 1- and 3-year cumulative local recurrence rates were 5.1% and 14.1%, respectively, in the LPE group and 8.0% and 15.1%, respectively, in the OPE group (both P>0.05). Conclusions: In locally advanced rectal cancer patients, LPE is associated with shorter operative time, less intraoperative blood loss, fewer perioperative complications, and shorter hospital stay compared with OPE. It is safe and feasible without compromising oncological effect.

Interpretation of Chinese expert consensus on the pelvic exenteration for primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) / 中华胃肠外科杂志

The China PelvEx Collaborative, under the direction of Colorectal Cancer Committee of the Chinese Medical Doctor Association, Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health, has formulated and issued the Chinese expert consensus for primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) , with the academic support of the Chinese Journal of Gastrointestinal Surgery and Chinese Journal of Colorectal Disease (Electronic Edition). This Consensus refers to the expert consensus developed by the International PelvEx Collaboration, incorporates the latest international multi-center research results and combines the latest research results in China. The Consensus unifies some definitions, clarifies the surgical indications, and puts forward the definition and preventive measures of "empty pelvic syndrome" earlier. For the controversial classification of local recurrent rectal cancer, the Chinese classification was proposed for the first time in Consensus. At the same time, the definition of pelvic exenteration is controversial, and a more consistent cognition is proposed. It is believed that, with the in-depth research on complicated rectal cancer, C-PelvEx will gather more higher-level data from clinical research in several domestic centers, so as to further enrich the content of the updated Consensus.

Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats / 中国中药杂志

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Characterization of CircRNA-Associated CeRNA Networks in Folate Deficiency-Induced Neural Tube Defects / 生物医学与环境科学（英文）

OBJECTIVE@#Circular RNAs (circRNAs) participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases. This study aimed to investigate the role of circRNAs in neural tube defects (NTDs).@*METHOD@#We characterized circRNA-associated competitive endogenous RNA (ceRNA) networks in brain tissue of low folate -induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing. The expression levels of Circzfp644, miR-20-5p and Gas7 were detected by RT-PCR. Gas7 and Circzfp644 functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells (F9 cells), and luciferase gene reporter assay was assessed in the F9 cells. In addition, the expression levels of Circzfp644, miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues.@*RESULTS@#We detected 57 circRNA transcripts, 16 miRNAs, and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control (normal) tissues. Circzfp644 shared miRNA response elements with the growth arrest specific 7 ( Gas7) gene and competitively bound with miR-20-5p to increase the expression of Gas7. Downregulation of Circzfp644 and Gas7 and upregulation of miR-20-5p were found in human NTD tissue.@*CONCLUSION@#This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs.

Changes in process and outcome for ST elevation myocardial infarction in central China from 2011 to 2018 / 中华医学杂志(英文版)

BACKGROUND@#Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018.@*METHODS@#We compared the data from the Henan STEMI survey conducted in 2011-2012 ( n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 ( n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment.@*RESULTS@#STEMI patients in 2016-2018 were younger (median age: 63.1 vs . 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs . 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs . 82.7% [22,439/27,129], P <0.001). The proportion of patients treated by reperfusion within 12 h increased from 44.1% (546/1237) to 78.4% (2698/3440) ( P <0.001) with a prolonged median onset-to-first medical contact time (from 144 min to 210 min, P <0.001). The use of antiplatelet agents, statins, and β-blockers increased significantly. The risk of in-hospital mortality significantly decreased over time (6.1% [95/1548] vs . 4.2% [198/4748], odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.50-0.88, P = 0.005) after adjustment.@*CONCLUSIONS@#Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality. However, gaps persist between clinical practice and guideline recommendation. Public awareness, reperfusion strategies, and construction of chest pain centers need to be further underscored in central China.

Dong's extraordinary point needling technique combined with medication for postoperative complications of anal fistula: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Dong's extraordinary point needling technique on postoperative complications of anal fistula.@*METHODS@#A total of 241 patients undergoing anal fistula surgery were randomly divided into an observation group (121 cases, 3 cases dropped off) and a control group (120 cases, 2 cases dropped off). The patients in the control group were treated with intramuscular injection of compound diclofenac sodium injection and oral administration of tamsulosin hydrochloride sustained release capsules. In addition to the treatment in the control group, the patients in the observation group were treated with Daoma needling technique at the "Sanqi points" (Qimen point, Qijiao point, and Qizheng point) combined with Dongqi needling technique at "Sanhuang points" (sub-Tianhuang point, Dihuang point, Renhuang point), with each session lasting 30 min. The treatment in the two groups both started on the first day after surgery, and was given once daily for 14 consecutive days. Visual analog scale (VAS) score was compared between the two groups on postoperative day 1, 7, and 14; bladder residual urine volume, spontaneous voiding volume, and urinary catheterization frequency were assessed after treatment on postoperative day 1; and anorectal dynamic indexes (anal canal resting pressure, rectal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold) were evaluated before surgery and on postoperative day 4. Clinical efficacy was assessed in both groups one month after surgery.@*RESULTS@#On postoperative day 7 and 14, the VAS scores of both groups were lower than those on postoperative day 1 (P<0.05), and the VAS scores in the observation group were lower than those in the control group (P<0.05). The bladder residual urine volume and urinary catheterization frequency in the observation group were lower than those in the control group (P<0.05), while the spontaneous voiding volume was higher than that in the control group (P<0.05). On postoperative day 4, the anal canal resting pressure, maximum squeeze pressure of the anal canal, and the minimum rectal sensory threshold were lower than preoperative values (P<0.05), while the rectal resting pressure was higher than preoperative value (P<0.05) in both groups. The anal canal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold were lower than those in the control group, and the rectal resting pressure was higher than that in the control group (P<0.05). The effective rate was 93.2% (110/118) in the observation group, which was higher than 84.7% (100/118) in the control group (P<0.05).@*CONCLUSION@#Dong's extraordinary point needling technique could reduce postoperative pain, alleviate urinary retention, and improve defecation in patients undergoing anal fistula surgery.

Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA‍-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis / 中国当代儿科杂志

OBJECTIVES@#To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC).@*METHODS@#Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota.@*RESULTS@#Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora.@*CONCLUSIONS@#Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

Minimally invasive surgical technique for the treatment of congenital double aortic arch / 中国胸心血管外科临床杂志

@#Objective    To summarize the treatment results of double aortic arch (DAA) by minimally invasive surgical technique. Methods    We retrospectively analyzed the clinical data of DAA patients who underwent minimally invasive surgeries in our center between October 2016 and August 2021. Results    There were 11 males and 4 females with a mean age of 3-61 (20.00±18.80) years. There were 8 patients of DAA and 7 patients of DAA complicated with distal left-sided aortic arch atresia and ligamentum connection. All patients received operations through minimal subaxillary incision, 13 patients were through left side and 2 patients were through right side. One patient with ventricular septal defect was performed operations concurrently under the cardiopulmonary bypass through right minimal subaxillary incision. All patients had symptom improvement without surgery related complications or death in postoperative period. The duration of operation was 30-192 (61.93±40.19) min and mechanical ventilation time was 2-9 (5.33±2.53) h. The length of ICU stay was 18-124 (51.00±38.07) h and hospital stay time was 8-21 (12.67±3.42) d. All patients had sympto-matic relief with good growth and exercise tolerance during the follow-up of 6 (3, 9) months. Conclusion    Minimally invasive surgical technique is a safe, effective and cosmetic approach with good results for DAA treatment.

The prognostic and predictive value of plasma D-dimer in children with neuroblastoma: a 7-year retrospective analysis at a single institution

Purpose@#Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. @*Methods@#A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020.Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. @*Results@#Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. @*Conclusion@#A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.

Binder jet 3D printing composite bilayer tablet of extended-release printing technology in the study / 药学学报

Based on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.