Aim To investigate the preventive and therapeutic effect of crocetin(Cro)on acute intestinal injury induced by radiation(RT)and its related mech-anism.Methods Forty mice were randomly divided into four groups:control group,radiation group(RT group),low-dose Cro intervention group(RT+Low-dose Cro group)and high-dose Cro intervention group(RT+High-dose Cro group).The RT group was given a single dose of 12Gy radiation to the abdomen.The Cro intervention group was treated with 25 mg·kg-1 and 100 mg·kg-1 Cro by gavage once a day before ra-diation until seven days after radiation.The mice in each group were weighed.The morphology of intestinal tissue was observed by HE staining.The levels of in-testinal inflammatory factors and oxidative stress were detected.The expressions of Lgr5,Ki67,lysozyme,ZO-1 and Occludin in small intestine tissuewere detected by immunohistochemistry.The expressions of Nrf2/HO-1 and NF-κB signaling related proteinswere detected by Western blot.Results Compared to the control group,mice in the RT group exhibited a significant decrease in body weight(P＜0.01).Additionally,they dis-played evident morphological damage to the small in-testine and elevated levels of pro-inflammatory factors(TNF-α,IL-6)as well as oxidative stress markers(in-creased ROS and MDA levels,decreased GSH and SOD activities)(P＜0.01).Moreover,there was an in-crease in Lgr5 and Ki67 positive cells within the crypts(P＜0.01).The expressions of Occludin,lysozyme,ZO-1,and HO-1 were reduced in small intestine while Nrf2,p-p65,and p-IκB expressions increased(P＜0.01).The improvements in the Cro group were sig-nificantly greater than the RT group(P＜0.01),with a more pronounced effect observed in the high-dose group.Conclusions Cro has a preventive and thera-peutic effect on radiation-induced intestinal injury,and its mechanism is related to anti-inflammation,anti-oxi-dation,improvement of intestinal barrier function,pro-motion of intestinal stem cell regeneration,enhance-ment of Nrf2/HO-1 signaling and reduction of NF-κB signaling activity.

Aim To investigate the preventive and therapeutic effect of crocetin(Cro)on acute intestinal injury induced by radiation(RT)and its related mech-anism.Methods Forty mice were randomly divided into four groups:control group,radiation group(RT group),low-dose Cro intervention group(RT+Low-dose Cro group)and high-dose Cro intervention group(RT+High-dose Cro group).The RT group was given a single dose of 12Gy radiation to the abdomen.The Cro intervention group was treated with 25 mg·kg-1 and 100 mg·kg-1 Cro by gavage once a day before ra-diation until seven days after radiation.The mice in each group were weighed.The morphology of intestinal tissue was observed by HE staining.The levels of in-testinal inflammatory factors and oxidative stress were detected.The expressions of Lgr5,Ki67,lysozyme,ZO-1 and Occludin in small intestine tissuewere detected by immunohistochemistry.The expressions of Nrf2/HO-1 and NF-κB signaling related proteinswere detected by Western blot.Results Compared to the control group,mice in the RT group exhibited a significant decrease in body weight(P＜0.01).Additionally,they dis-played evident morphological damage to the small in-testine and elevated levels of pro-inflammatory factors(TNF-α,IL-6)as well as oxidative stress markers(in-creased ROS and MDA levels,decreased GSH and SOD activities)(P＜0.01).Moreover,there was an in-crease in Lgr5 and Ki67 positive cells within the crypts(P＜0.01).The expressions of Occludin,lysozyme,ZO-1,and HO-1 were reduced in small intestine while Nrf2,p-p65,and p-IκB expressions increased(P＜0.01).The improvements in the Cro group were sig-nificantly greater than the RT group(P＜0.01),with a more pronounced effect observed in the high-dose group.Conclusions Cro has a preventive and thera-peutic effect on radiation-induced intestinal injury,and its mechanism is related to anti-inflammation,anti-oxi-dation,improvement of intestinal barrier function,pro-motion of intestinal stem cell regeneration,enhance-ment of Nrf2/HO-1 signaling and reduction of NF-κB signaling activity.

Objective To observe the effects of whole-course epidural analgesia with ropivacaine injection and sufentanil injection on hemodynamics,stress response and postoperative pain in patients undergoing thoracoscopic lobectomy.Methods Patients who underwent thoracoscopic lobectomy were divided into the treatment group and the control group according to the cohort method.Both groups underwent epidural puncture and catheterization before surgery.The control group was given bolus injection of 10 mg of 0.125％ropivacaine hydrochloride injection and 0 9％NaCl injection(8 mL in total)via epidural catheter.The treatment group was given bolus injection of 10 mg of 0.125％ropivacaine hydrochloride injection and 4 μg of 0.5 μg·mL-1 sufentanil citrate injection(8 mL in total)via epidural catheter.Analgesia was maintained with the same concentration of drugs during the surgery.The epidural analgesia pump was used before closing the pleura.The analgesic formula for the control group consisted of 400 mg of 0.125％ropivacaine hydrochloride injection,and the analgesic formula for the treatment group consisted of 400 mg of 0.125％ropivacaine hydrochloride injection and 0.5 mg of 0.5 μg·mL-1 sufentanil citrate injection.Changes in hemodynamic indicators[heart rate(HR),mean arterial pressure(MAP)],serum epinephrine(E),norepinephrine(NE)and cortisol(Cor)during surgery,occurrence of postoperative acute pain,postoperative remedial analgesia,and chronic pain were compared between the two groups.Safety was evaluated.Results A total of 80 patients were enrolled in the study,with 38 in the control group and 42 in the treatment group.The heart rates(HR)of the treatment and control groups were(80.35±9.62)and(88.24±10.35)beat·min-1 at immediate tracheal intubation(T1);and their mean arterial pressures(MAP)were(95.07±8.51)and(98.46±9.05)mmHg respectively.At skin incision(T2),HR of the treatment and control groups were(75.33±9.21)and(80.65±10.63)beat·min-1,respectively;MAP were(94.33±8.43)and(99.06±6.58)mmHg,respectively.Post-operation(T4),serum levels of E in the treatment and control groups were(53.17±9.79)and(60.79±8.58)ng·L-1;NE levels were(52.33±8.22)and(59.96±8.89)ng·L-1;Cor levels were(22.75±4.63)and(28.64±5.02)mg·L-1.At 24 hours post-operation(T5),serum levels of E in the treatment and control groups were(54.27±9.15)and(62.28±8.33)ng·L-1;NE levels were(55.34±9.18)and(62.07±9.58)ng·L-1;Cor levels were(24.19±4.52)and(30.57±4.79)mg·L-1.The incidences of agitation post-operation were 7.14％(3 cases/42 cases)and 23.68％(9 cases/38 cases),and the time to patient controlled epidural analgesia(PCEA)press was(13.67±2.74)and(11.35±2.28)h,respectively.The cumulative rescue analgesic dose within 72 h post-operation were(120.73±34.36)and(156.35±36.79)mg,respectively.Statistical analysis showed significant differences between the treatment and control groups in all these indicators(all P＜0.05).The total incidences of adverse drug reactions in the treatment group and the control group were 30.95％(13 cases/42 cases)and 23.68％(9 cases/38 cases),without statistically significant difference between the groups(all P＞0.05).Conclusion Applying ropivacaine combined with sufentanil in whole-course epidural analgesia for patients undergoing thoracoscopic lobectomy is conducive to maintaining perioperative hemodynamic stability,alleviating surgical stress and postoperative pain,and reduce the incidence of postoperative agitation.

Objective To observe the effects of whole-course epidural analgesia with ropivacaine injection and sufentanil injection on hemodynamics,stress response and postoperative pain in patients undergoing thoracoscopic lobectomy.Methods Patients who underwent thoracoscopic lobectomy were divided into the treatment group and the control group according to the cohort method.Both groups underwent epidural puncture and catheterization before surgery.The control group was given bolus injection of 10 mg of 0.125％ropivacaine hydrochloride injection and 0 9％NaCl injection(8 mL in total)via epidural catheter.The treatment group was given bolus injection of 10 mg of 0.125％ropivacaine hydrochloride injection and 4 μg of 0.5 μg·mL-1 sufentanil citrate injection(8 mL in total)via epidural catheter.Analgesia was maintained with the same concentration of drugs during the surgery.The epidural analgesia pump was used before closing the pleura.The analgesic formula for the control group consisted of 400 mg of 0.125％ropivacaine hydrochloride injection,and the analgesic formula for the treatment group consisted of 400 mg of 0.125％ropivacaine hydrochloride injection and 0.5 mg of 0.5 μg·mL-1 sufentanil citrate injection.Changes in hemodynamic indicators[heart rate(HR),mean arterial pressure(MAP)],serum epinephrine(E),norepinephrine(NE)and cortisol(Cor)during surgery,occurrence of postoperative acute pain,postoperative remedial analgesia,and chronic pain were compared between the two groups.Safety was evaluated.Results A total of 80 patients were enrolled in the study,with 38 in the control group and 42 in the treatment group.The heart rates(HR)of the treatment and control groups were(80.35±9.62)and(88.24±10.35)beat·min-1 at immediate tracheal intubation(T1);and their mean arterial pressures(MAP)were(95.07±8.51)and(98.46±9.05)mmHg respectively.At skin incision(T2),HR of the treatment and control groups were(75.33±9.21)and(80.65±10.63)beat·min-1,respectively;MAP were(94.33±8.43)and(99.06±6.58)mmHg,respectively.Post-operation(T4),serum levels of E in the treatment and control groups were(53.17±9.79)and(60.79±8.58)ng·L-1;NE levels were(52.33±8.22)and(59.96±8.89)ng·L-1;Cor levels were(22.75±4.63)and(28.64±5.02)mg·L-1.At 24 hours post-operation(T5),serum levels of E in the treatment and control groups were(54.27±9.15)and(62.28±8.33)ng·L-1;NE levels were(55.34±9.18)and(62.07±9.58)ng·L-1;Cor levels were(24.19±4.52)and(30.57±4.79)mg·L-1.The incidences of agitation post-operation were 7.14％(3 cases/42 cases)and 23.68％(9 cases/38 cases),and the time to patient controlled epidural analgesia(PCEA)press was(13.67±2.74)and(11.35±2.28)h,respectively.The cumulative rescue analgesic dose within 72 h post-operation were(120.73±34.36)and(156.35±36.79)mg,respectively.Statistical analysis showed significant differences between the treatment and control groups in all these indicators(all P＜0.05).The total incidences of adverse drug reactions in the treatment group and the control group were 30.95％(13 cases/42 cases)and 23.68％(9 cases/38 cases),without statistically significant difference between the groups(all P＞0.05).Conclusion Applying ropivacaine combined with sufentanil in whole-course epidural analgesia for patients undergoing thoracoscopic lobectomy is conducive to maintaining perioperative hemodynamic stability,alleviating surgical stress and postoperative pain,and reduce the incidence of postoperative agitation.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Classical famous prescription Dihuang Yinzi is widely used in modern clinical practice，and can treat many kinds of diseases，especially the diseases of nervous system in internal medicine. Its clinical effect is accurate，but it has not been converted into Chinese patent medicine preparations. Therefore，the authors have collected ancient traditional Chinese medicine（TCM） literatures of Dihuang Yinzi by the methods of bibliometrics，and selected and sorted out 254 pieces of effective data， involving 144 ancient books of TCM，and systematically summarized and analyzed the historical development origin，main treatment syndrome，formula making principle，dosage，preparation method，decoction method and medicine taking method of Dihuang Yinzi，in order to provide the ancient literary evidence support for the development and clinical application of classic famous prescriptions. It is found that Dihuang Yinzi was from Xuanming Lunfang written by LIU He-jian，a doctor of Jin dynasty. It was composed of 12 kinds of herbs，namely Rehmanniae Radix Praeparata，Morindae Officinalis Radix，Corni Fructus，Cistanches Herba，Dendrobii Caulis，Aconm Lateralis Radix Praeparaia，Schisandrae Chinensis Fructus，Cinnamomi Ramulus，Poria，maimendong，Acori Calami Rhizoma and Polygalae Radix, and mainly used for the treatment of Yinfei. The later records of Dihuang Yinzi mostly followed the prescription composition and main treatment set forth in Xuanming Lunfang，and its clinical application was expanded. In the 199 articles with the indications for disease treatment，Yinfei was the most commonest indication, and took up about half of the total，which was followed by stroke，taking up about two fifths of the total. It was also used for the treatment of sudden aphonia，flaccidity syndrome，vertigo，enuresis. Dihuang Yinzi has a wide range of treatment，but the pathogenes is always belongs to "the deficiency of water and fire in the kidney". The recipe of Dihuang Yinzi was unique，and can be used to treat both the upper and lower parts of the body，as well as both the outward symptoms and root causes of an illness at the same time， in particular，it mainly focuses on the treatment of the lower and the root. Among the 56 literatures with drug dosage records，about one third of them inherited the records of Xuanming Lunfang: "Equal division，the top is the end，3 qian for each dose." The dosage was generally light. The preparations are mostly decoction and boiled powder. In the decocting and taking methods，it was suggested that "turbid medicine shall be boiled for a short time，and taken after several boilings，with no limit to time."

Adult ; Cladribine/therapeutic use* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans

Rheumatoid arthritis(RA) is a chronic autoimmune disease, belonging to the "Arthromyodynia (Bi Zheng)" category in traditional Chinese medicine. However, the ethnomedicine has a unique understanding of RA, with a long-term clinical experience accumulation and significant efficacy in the treatment of RA, and it has now become one of the important means in treatment of RA. On the basis of literature research, the understanding of RA and commonly used Tibetan medicine, Mongolian medicine, Hui medicine and other herbs and preparations were reviewed in this paper, with the aim of providing a reference for its clinical treatment of RA and research and development of innovative drugs.