The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hydrazines/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy*

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Objective: To investigate the risk factors of scrub typhus complicated with acute respiratory distress syndrome (ARDS) and provide help for the prevention and treatment of this severe disease. Methods: A retrospective analysis on the clinical data of 176 scrub typhus patients in the First Affiliated Hospital of Guangxi Medical University from 2009 to 2016 was conducted. The patients were divided into ARDS group (n=25) and non-ARDS group (n=151). Age, sex, the time from onset to diagnosis, clinical characteristics, laboratory examinations within 24 hours of admission, and acute physiology and chronic health evaluation (APACHE)Ⅱscore were recorded. The differences of clinical characteristics between two groups were compared, and the relevant factors were analyzed. Chi-square test, t-test, and Mann-Whitney U test were chosen for the comparison of categorical data and measurement data of normal or non-normal distribution, respectively, then statistically significant variables were included into logistic regression analysis. Results: Fever (100.0%) was the most common clinical feature and elevated alanine aminotransferase (95.4%) was the most frequent laboratory abnormality. Age (t=3.055), APACHEⅡscore (t=5.592), D-dimer (t=2.704), the time from onset to diagnosis (t=5.719), serum level of creatinine (t=4.099), and the incidence of hepatosplenomegaly (χ²=5.202) in ARDS group were all higher than those in non-ARDS group (all P<0.05), while the platelet count, serum level of albumin in ARDS group were both lower than those in non-ARDS group (both P<0.05). Multiple factor logistic regression analysis demonstrated that age, APACHEⅡscore, D-dimer, the time from onset to diagnosis, and the platelet count were independent risk factors for scrub typhus complicated with ARDS. Fifteen patients died among the 176 cases, with eight (32%) in the ARDS group and seven (4.6%) in the non-ARDS group, the difference between the two groups was statistically significant (χ²=20.6, P<0.01). Conclusion Patients with scrub typhus should be definitely diagnosed at an early stage. Meanwhile, monitoring the risk factors of scrub typhus patients complicated with ARDS, and taking effective treatment can improve the prognosis of scrub typhus patients.

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level. On pathological analysis of the biopsied liver tissue, hepatocyte ballooning and cholestatic multinucleate giant cells were noted. The lobular architecture was distorted. Infiltration of inflammatory cells, predominantly lymphocytes, was seen in the portal tracts. In response to the anti-inflammatory and liver protective drugs as well as fat-soluble vitamins over 2 months, the bilirubin and transaminases levels were improved markedly while the TBA kept elevated. Because of persisting hypercholanemia on the follow-up, SLC10A1 gene analysis was performed at his age of 17.2 months. The child proved to be a homozygote of the reportedly pathogenic variant c.800C>T (p. Ser267Phe), while the parents were both carriers. NTCP deficiency was thus diagnosed. The infant was followed up until 34.3 months old. He developed well in terms of the anthropometric indices and neurobehavioral milestones. The jaundice disappeared completely. The liver size, texture and function indices all recovered. However, the hypercholanemia persisted, and the long-term outcome needs to be observed.
Humans ; Infant ; Male ; Organic Anion Transporters, Sodium-Dependent ; deficiency ; genetics ; Symporters ; deficiency ; genetics

Progressive familial intrahepatic cholestasis type II (PFIC-2) is an autosomal recessive disorder caused by biallelic variants of ABCB11 gene. This paper reports the clinical and laboratory features of a pediatric patient with PFIC-2. The patient was a 2.4-month-old male infant with jaundice and hepatomegaly as the main clinical manifestations. The serum levels of total bilirubin, direct bilirubin and total bile acids were increased, while the serum γ-glutamyl transpeptidase (GGT) level was normal. Next generation sequencing revealed two missense variants, c.1493T>C(p.Ile498Thr) and c.1502T>G(p.Val501Gly), in the ABCB11 gene of the patient, which were inherited from his father and mother, respectively. The latter was a novel variant which was predicted to be pathogenic by using a variety of bioinformatic tools, and the affected p.Val501 residue was highly conserved in 112 homologous peptides.

Objective To study paraquat adsorbability of different field soils in Guangxi province of China. Methods HPLC method was adopted to measure the peak area of paraquat in three different media of four types of soils. Chromatographic column was Kromasil C18 column (4. 6 mm×200 mm, 5 μm); mobile phase was acetonitrile-water (including 0. 03 mol·L-1 sodium heptanesulfonate and 0. 24 mol·L-1 phosphoric acid) at a ratio of 397 (pH adjusted to 2. 0 by triethylamine). Detection wave length was 258 nm; column temperature was 25 ℃; the injection volume was 20 μL; flow rate was 0. 8 mL·min-1 . The peak areas of paraquat before and after being adsorbed were compared to calculate the adsorption rate of paraquat in different soils. Results All tested soil samples possessed the adsorption rate of paraquat over 99. 0%. Conclusion Four common field soils in Guangxi province can be used as temporary effective absorbents for the first-aid of paraquat poisoning.