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1.
Am J Med Sci ; 367(6): 375-381, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38467374

ABSTRACT

BACKGROUND: Our study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). METHODS: We enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. RESULTS: Among the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882-0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682-0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137-1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962-0.993, P = 0.005) were related to the development of PH. CONCLUSIONS: Patients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.


Subject(s)
Hemodynamics , Hypertension, Pulmonary , Pulmonary Disease, Chronic Obstructive , Sleep Apnea, Obstructive , Humans , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/etiology , Male , Female , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/complications , Retrospective Studies , Aged , Cardiac Catheterization
2.
Eur J Med Chem ; 246: 114960, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36462445

ABSTRACT

Growing antibiotic resistance is causing a health care crisis, leading to an urgent need for new antibiotics to tackle serious hospital and community infections. Pleuromutilin, a naturally occurring product with moderate antibacterial activity, has a unique structure that has attracted great efforts to modify its scaffold to obtain lead compounds. Herein, we report the synthesis of a series of novel pleuromutilin derivatives with a scaffold of 4(3H)-quinazolinone or its analogues at the C-14 side chain and investigated their in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis as well as Gram-negative bacteria (Escherichia coli and Salmonella enterica subsp. enterica serovar pullorum). Structure-activity relationship (SAR) studies showed that the substituents on the benzene ring of 4(3H)-quinazolinone was not as important as the substituted position to improve antibacterial activity while the substituted groups on the N-3 position of 4(3H)-quinazolinone had strong impact on the efficacy. The replacement of the benzene moiety of 4(3H)-quinazolinone with other rings (pyridine, pyrrole, thiophene, or cyclopentyl) also showed high antibacterial efficacy, meaning the benzene ring was dispensable for exerting powerful antibacterial properties. In vitro pharmacokinetics investigations and cytotoxicity assays indicated that 2-mercapto-4(3H)-quinazolinone scaffold was superior to 2-(piperazin-1-yl)quinazolin-4(3H)-one. Among this series of pleuromutilin analogues, compound 23 with a structure of 2-mercapto-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one displayed the best in vitro antibacterial activity against MRSA (MIC = 0.063 µg/mL) and low cytotoxicity to RAW 264.7 cells (IC50>100 µM) and was demonstrated to inhibit MRSA effectively in a mouse thigh infection model, outperforming the comparator, tiamulin.


Subject(s)
Diterpenes , Methicillin-Resistant Staphylococcus aureus , Polycyclic Compounds , Animals , Mice , Anti-Bacterial Agents/chemistry , Benzene/pharmacology , Diterpenes/pharmacology , Escherichia coli , Methicillin Resistance , Microbial Sensitivity Tests , Polycyclic Compounds/pharmacology , Quinazolinones/pharmacology , Structure-Activity Relationship , Pleuromutilins
3.
Chem Biodivers ; 18(12): e2100687, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34726832

ABSTRACT

Toxoplasmosis post serious threaten to human health, leading to severely eye and brain disease, especially for immunocompromised patients and pregnant women. The multiple side effects and long dosing period of current main treatment regiments calls for high effective and low toxicity anti-toxoplasmosis drugs. Herein, we report our efforts to synthesize a series of 2-(piperazin-1-yl)quinazolin-4(3H)-one derivatives and investigate their activity against Toxoplasma gondii tachyzoites in vitro based on cell phenotype screening. Among the 26 compounds, 8w and 8x with diaryl ether moiety at the side chain of piperazine exhibited good efficacy to inhibit T. gondii, with IC50 values of 4 µM and 3 µM, respectively. Structure-activity relationship (SAR) studies implies that hydrophobic aryl at the side chain would be preferred for improvement of activity. Molecular docking study reveals these two compounds appeared high affinity to TgCDPK1 by interaction with the hydrophobic pocket of ATP-binding cleft.


Subject(s)
Antiprotozoal Agents/pharmacology , Quinazolinones/pharmacology , Toxoplasma/drug effects , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Dose-Response Relationship, Drug , Molecular Docking Simulation , Molecular Structure , Parasitic Sensitivity Tests , Quinazolinones/chemical synthesis , Quinazolinones/chemistry
5.
Chin Med J (Engl) ; 133(9): 1025-1031, 2020 May 05.
Article in English | MEDLINE | ID: mdl-32044814

ABSTRACT

BACKGROUND: The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adult , Aged , Aged, 80 and over , COVID-19 , China , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Fever/etiology , Humans , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2 , Tertiary Care Centers , Tomography, X-Ray Computed , Young Adult
6.
Eur J Med Chem ; 183: 111711, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31585276

ABSTRACT

Toxoplasma gondii severely threaten the health of immunocompromised patients and pregnant women as this parasite can cause several disease, including brain and eye disease. Current treatment for toxoplasmosis commonly have high cytotoxic side effects on host and require long durations ranging from one week to more than one year. The regiments lack efficacy to eradicate T. gondii tissue cysts to cure chromic infection results in the needs for long treatment and relapsing disease. In addition, there has not been approved drugs for treating the pregnant women infected by T. gondii. Moreover, Toxoplasma vaccine researches face a wide variety of challenges. Developing high efficient and low toxic agents against T. gondii is urgent and important. Over the last decade, tremendous progress have been made in identifying and developing novel compounds for the treatment of toxoplasmosis. This review summarized and discussed recent advances between 2009 and 2019 in exploring effective agents against T. gondii from five aspects of drug discovery.


Subject(s)
Antiprotozoal Agents , Drug Discovery , Toxoplasma/drug effects , Toxoplasmosis/drug therapy , Animals , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Female , Humans , Pregnancy
7.
Eur J Med Chem ; 162: 194-202, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30445267

ABSTRACT

A series of novel pleuromutilin derivatives embracing 7H-pyrrolo[2,3-d]pyrimidine moiety were synthesized and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative pathogens as well as in vivo efficacy in lethal systemic infected mice. Most compounds displayed good in vitro potency against MSSA, MRSA, MSSE, MRSE and E. faecium (MIC = 0.0625-4 µg/mL), especially 15a, 15b and 15o showed excellent activity that even more active than the comparator valnemulin. The in vivo efficacy investigation exhibited compound 15a (ED50 = 16.0 mg/kg) had comparable activity to valnemulin (ED50 = 13.5 mg/kg). The results provided by the dose-response study demonstrated 15a can supply infected mice with 70% survival rate at dose of 40 mg/kg via intragastric (i.g.) administration.


Subject(s)
Anti-Bacterial Agents/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Bacterial Infections/drug therapy , Diterpenes/chemical synthesis , Diterpenes/chemistry , Diterpenes/pharmacology , Dose-Response Relationship, Drug , Mice , Polycyclic Compounds , Pyrimidines , Survival Rate , Pleuromutilins
8.
Arch Pharm (Weinheim) ; 352(1): e1800266, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30536467

ABSTRACT

To develop new antibiotics owning a special mechanism, we used the molecular assembly method to synthesize a series of novel pleuromutilin derivatives containing a cinnamic acid scaffold at the C-14 side chain. We evaluated their antibacterial activity and used in silico molecular docking to study their binding mode with the target. The structure-activity relationship (SAR) study suggested that compounds with NO2 (13e), OH (13u), and NH2 (13y) appeared more active (0.0625-2 µg/mL) in vitro against several penicillin-resistant Gram-positive bacteria and the position of the substituent on the benzene ring would affect the activity. The in vivo efficacy investigation of 13e, 13u, and 13y with once daily intragastric (i.g.) administration at 40 mg/kg for 3 consecutive days in a mouse systemic infection model showed that 13u had equal activity as valnemulin providing the mice with 60% survival, while 13e and 13y gave 30 and 40% survival, respectively. The molecular docking studies indicated that π-π stacking and hydrogen bond formation played important roles in improving the antibacterial activity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cinnamates/pharmacology , Molecular Docking Simulation , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cinnamates/chemistry , Diterpenes/chemical synthesis , Diterpenes/chemistry , Diterpenes/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Polycyclic Compounds , Pleuromutilins
9.
J BUON ; 22(6): 1422-1427, 2017.
Article in English | MEDLINE | ID: mdl-29332333

ABSTRACT

PURPOSE: Green tea (Camellia sinensis) is considered as a rich source of epigallocatechin gallate (EGCG) which has been shown to exert impressive pharmacological properties. The anticancer properties of EGCG have been extensively studied however, its anticancer activity has not been explored in lung cancer. The present study was therefore designed to evaluate the anticancer effects of EGCG against non-small cell lung cancer (NSCLC) cell line A-549 and normal human fibroblast FR-2 cells. METHODS: Cell viability was assessed by CCK8 assay, apoptosis by DAPI, annexin V/propidium iodide (PI) and flowcytometery and cell cycle analysis by flow cytometry. Cell migration capacity was investigated by wound-healing assay and protein expression was examined by Western blotting. RESULTS: The results revealed that EGCC could inhibit the proliferation of A-549 cells in a concentration-dependent manner and exhibited an IC50 of 25 µM against the IC50 of 100 µM against the normal human fibroblasts. Further evaluation revealed that EGCG exerts its anticancer effects via induction of apoptosis, modulation of Bax/blc-2 ratio and by triggering G2/M cell cycle arrest. Furthermore, EGCG could also inhibit the migration of A5-49 cells in a concentration-dependent manner. CONCLUSION: In conclusion, based on our results, we believe that EGCG could prove to be an important lead molecule for the treatment of lung cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Catechin/analogs & derivatives , Cell Cycle Checkpoints/drug effects , Cell Movement/drug effects , Lung Neoplasms/drug therapy , Tea/chemistry , Carcinoma, Non-Small-Cell Lung/pathology , Catechin/pharmacology , Catechin/therapeutic use , Cell Line, Tumor , Humans , Lung Neoplasms/pathology
10.
J Proteome Res ; 11(4): 2365-73, 2012 Apr 06.
Article in English | MEDLINE | ID: mdl-22428589

ABSTRACT

As inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins have pleiotropic vascular-protective effects, such as anti-inflammatory and antioxidative effects. We investigated the short-term beneficial effects of statins on modulating the translocation of lipid-raft-related proteins in endothelial cells (ECs). Human umbilical vein ECs were treated with atorvastatin for 30 min or 2 h; lipid-raft proteins were isolated and examined by quantitative proteome assay. Functional classification of identified proteins in lipid rafts revealed upregulated antioxidative proteins; downregulated proteins were associated with inflammation and cell adhesion. Among proteins verified by Western blot analysis, endoplasmic reticulum protein 46 (ERp46) showed increased level in lipid rafts with atorvastatin. Further, atorvastatin inhibited the activation of membrane-bound NADPH oxidase in both untreated and angiotensin II-treated ECs, as shown by reduced reactive oxygen species production. Co-immunoprecipitation and immunofluorescence experiments revealed that atorvastatin increased the association of ERp46 and Nox2, an NADPH oxidase isoform, in lipid rafts, thereby inhibiting Nox2 assembly with its regulatory subunits, such as p47phox and p67phox. Our results reveal a novel antioxidative role of atorvastatin by promoting the membrane translocation of ERp46 and its binding with Nox2 to inhibit Nox2 activity in ECs, which may offer another insight into the pleiotropic functions of statins.


Subject(s)
Antioxidants/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Membrane Microdomains/chemistry , Proteome/metabolism , Amino Acid Sequence , Atorvastatin , Heptanoic Acids/pharmacology , Human Umbilical Vein Endothelial Cells/chemistry , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Membrane Glycoproteins/analysis , Membrane Glycoproteins/metabolism , Membrane Microdomains/metabolism , Molecular Sequence Data , NADPH Oxidase 2 , NADPH Oxidases/analysis , NADPH Oxidases/metabolism , Protein Disulfide-Isomerases/analysis , Protein Disulfide-Isomerases/metabolism , Proteins/analysis , Proteins/classification , Proteins/metabolism , Proteome/analysis , Proteome/drug effects , Pyrroles/pharmacology , Reactive Oxygen Species/analysis , Reactive Oxygen Species/metabolism , Reproducibility of Results
11.
Article in Chinese | MEDLINE | ID: mdl-22316533

ABSTRACT

OBJECTIVE: To investigate the therapeutic effects and safety of extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS). METHODS: ECMO were initiated in 6 patients with ARDS, not responding to conventional mechanical ventilation. Oxygenation status, positive end-expiratory pressure (PEEP) level, and fraction of inspired oxygen [FiO(2)] were compared before and after treatment with ECMO, while the adverse effects of ECMO were recorded. RESULTS: In 6 cases, pulse blood oxygen saturation [SpO(2)] was elevated (0.45-0.92 up to 0.94-1.00), PEEP level [cm H(2)O, 1 cm H(2)O=0.098 kPa] and [FiO(2)] were lowered [PEEP: 10.0-22.0 down to 4.0-15.0; FiO(2): 1.00 down to 0.30-0.60] after treatment with ECMO. Of 6 cases, 2 patients with severe influenza A/H1N1 pneumonia finally died of shock; 1 patient with severe influenza A/H1N1 pneumonia and 1 patient with Klebsiella pneumoniae pneumonia were withdrawn from ECMO treatment because of deterioration of the disease. One patient suffering from Cytomegalovirus pneumonia and another with Acinetobacter baumannii pneumonia were successfully discharged from hospital with recovery. The main complications were bleeding and hemolysis. CONCLUSIONS: ECMO could improve gas exchange, oxygenation and partially replace pulmonary function. Patients with ARDS should be treated with ECMO early if artificial ventilation treatment was unresponsive.


Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome/therapy , Adult , Female , Humans , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , Treatment Outcome , Young Adult
12.
Heart Rhythm ; 8(6): 879-84, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21277998

ABSTRACT

BACKGROUND: Alteration in ventricular repolarization has been reported in patients with spinal cord injuries (SCIs). However, its clinical impact remains unclear. OBJECTIVE: The purpose of this study was to investigate the correlation between SCIs and ventricular repolarization and the associated clinical impact. METHODS: One hundred forty-four patients with an SCI were retrospectively reviewed and were divided into two groups (SCI level ≤ T6, n = 110; SCI level >T6, n = 34). The electrocardiograms were reviewed during acute phase (at emergency room) and chronic phase (>1 year). RESULTS: There were no differences in the underlying diseases or in ASIA score between the two groups, except there were more patients with tetraplegia among those with an SCI level ≤ T6. For the electrophysiological parameters from the electrocardiograms, the patients with an SCI level ≤ T6 had longer QTc and PR interval than those with an SCI level >T6 during acute phase. In the chronic phase, there were no differences in the electrophysiological parameters between the two groups. Only in patients with an SCI level ≤ T6 did a Kaplan-Meier analysis show that QTc prolongation could predict 30-day mortality after the acute injury. After multivariate Cox regression analysis, only tetraplegia and QTc prolongation were independent predictors of 30-day mortality (odds ratios 7.85 and 34.62, respectively). In patients with an SCI level ≤ T6, the QTc intervals were shorter in the chronic phase than those during the acute phase. CONCLUSION: QTc interval was associated with the level of acute SCI and predicted the 30-day mortality.


Subject(s)
Electrocardiography , Heart Ventricles/physiopathology , Spinal Cord Injuries/physiopathology , Ventricular Dysfunction/physiopathology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , ROC Curve , Retrospective Studies , Spinal Cord Injuries/complications , Spinal Cord Injuries/diagnosis , Survival Rate , Taiwan/epidemiology , Thoracic Vertebrae , Trauma Severity Indices , Ventricular Dysfunction/epidemiology , Ventricular Dysfunction/etiology
13.
Zhongguo Zhen Jiu ; 28(3): 187-90, 2008 Mar.
Article in Chinese | MEDLINE | ID: mdl-18447217

ABSTRACT

OBJECTIVE: To observe the therapeutic effect of acupuncture at Siguan points with Qinglong Baizei method on primary dysmenorrhea (PD) and to study the mechanism. METHODS: One hundred and eighty cases of PD were zandomly divided into group A, group B and group C, 60 cases in each group. Group A were treated by acupuncture at Hegu (LI 4) and Taichong (LR 3) with Qinglong Baiwei method; group B were treated by routine acupuncture with Sanyinjiao (SP 6), Ciliao (BL 32) selected as main points; and group C were treated by oral administration of Yueyueshu Decoction. After treatment of 3 months, the therapeutic effects were analyzed, and changes of hemorrheological indexes and prostaglandin level were observed. RESULTS: The cured rate and the total effective rate were 75.0% and 100.0% in group A, 60.0% and 95.0% in group B, and 25.0% and 90.0% in group C, respec tively, group A and B being significantly better than group C (P < 0.01). And the analgesic effects within 30 min of treatment in both group A and group B were significantly better than that in group C (P < 0.01), and that in group A was significantly better than that in group B (P < 0.01). CONCLUSION: Acupuncture at Siguan points with Qinglong Baiwei method has a significant therapeutic effect on primary dysmenorrhea. The possible mechanism is to relieve pain by improving blood circulation and inhibiting production of prostaglandin.


Subject(s)
Acupuncture Points , Acupuncture Therapy/methods , Dysmenorrhea/therapy , Adolescent , Adult , Dinoprost/blood , Dysmenorrhea/blood , Female , Humans , Medicine, Chinese Traditional
14.
Zhongguo Zhen Jiu ; 28(3): 194-6, 2008 Mar.
Article in Chinese | MEDLINE | ID: mdl-18447219

ABSTRACT

OBJECTIVE: To observe therapeutic effect of drug-separated moxibustion at Shenque (CV 8) for treatment of infantile autumn diarrhea. METHODS: One hundred and thirty-six cases were randomly divided into an obser vation group and a control group, 68 cases in each group. The observation group were treated with drug-separated moxibustion at Shenque (CV 8) and the control group with oral administration of Smecta. The mean diarrhea-stopping time, the negative conversion rate of Human Rotavirus antigen in stool after treatment for 72 h, and the markedly-effective rate and the total effective rate were observed after treatment for 6 days in the twO groups. RESULTS: The markedly-effective rate and the total effective rate were 79.4% and 94.1% in the observation group and 35.3% and 75.0% in the control group, respectively, with very significantly or significantly difference between the two groups (P < 0.01 or P < 0.05); the mean diarrhea-stopping time in the observation group was shorter than that in the control group (P < 0.01); the negative conversion rate of Human Rotavirus antigen in stool after treatment for 72 h was 88.2%0 in the observation group and 69.1% in the control group with a very significantly difference between the two groups (P < 0.01). CONCLUSION: Drug-separated moxibustion at Shenque (CV 8) has a significant therapeutic effect on infantile autumn diarrhea, helps negative conversion of Human Rotavirus antigen in stool and shortens duration of disease.


Subject(s)
Acupuncture Points , Diarrhea, Infantile/therapy , Moxibustion/methods , Female , Humans , Infant , Infant, Newborn , Male , Medicine, Chinese Traditional
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