Objective To observe the curative effect of comprehensive traditional Chinese medicine(TCM)therapy for the treatment of refractory sudden hearing loss(i.e.,suffering sudden hearing loss more than 2 weeks),and to analyze the factors that may affect the prognosis.Methods A retrospective analysis was carried out in 405 hospitalized patients with refractory sudden hearing loss who were treated in the Department of Otorhinolaryngology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2005 to 2022.The patients were all treated by comprehensive TCM therapy including oral administration of Chinese medicine,acupuncture,acupoint seed-pressing application after individualized syndrome differentiation.The overall clinical efficacy was evaluated,and the difference of efficacy in the patients with various courses of disease,degrees of deafness,types of hearing curve,concomitant symptoms and TCM syndrome types,having or not having previous treatment history was analyzed.Results For the 405 patients with refractory sudden hearing loss,the cure rate was 5.7％and the total effective rate was 28.1％.Among the 405 patients,the best efficacy was achieved in the patients with mild hearing loss,low-frequency decline type of hearing curve,and having no previous treatment history,and the differences were statistically significant(P＜0.05 or P＜0.01).There was no significant difference in the efficacy of patients with different courses of disease,with or without concomitant symptoms,or with various syndrome types(P＞0.05).Conclusion The comprehensive TCM therapy has a certain effect on refractory sudden hearing loss.Patients with poor efficacy after conventional western medicine can still benefit from the comprehensive TCM therapy.

Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

Objective:To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors.Methods:Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children′s Medical Center, Shanghai Jiaotong University and Singapore KK Women′s and Children′s Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods.Results:There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months.Conclusions:NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.

"Assessing the quality by distinguishing features of traditional Chinese medicinal materials" is a characteristic quality evaluation system of traditional Chinese medicine, and it is also the basis of "Rating according to characters and setting the price by the grade" on the market. Astragali Radix was regarded as a famous traditional Chinese medicine (TCM), and this paper has carried out herbal textual research on the development and formation of the concept, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix. The authentic medicine producing areas of Astragalus in China have experienced a great change, Gansu , Sichuan and adjacent areas before the Tang Dynasty; Shanxi during the Tang and Song Dynasty. The concept, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix was formed in the Song and Ming Dynasty and still used today, which described as that the shape is "straight as an arrow"; the texture is "soft as cotton"; the section looks like" gold well and jade hurdle"; it was sweet in taste and has beany flavor. The system, "assessing the quality by distinguishing features of traditional Chinese medicinal materials", of Astragali Radix has undergone the adjustments from "true or false" to "good or bad", advance with the times, pick out the advantages from others and absorb the experience of traditional identification actively. Besides, it always returns to laconism from erudition and was summarized highly. Assessing the quality by distinguishing features of traditional Chinese medicinal materials and commodity specifications have the same root, so the former has reference meaning to revise the latter.

Objective To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro. Methods The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells. Results The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity. Conclusion The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.

Objective To analyze the effect and safety of profile pegylated interferon α-2a (PEG-IFN-α-2a) combined with ribavarin on hepatitis C virus (HCV)-related cirrhosis patients after splenic embolization.Methods Sixty-four HCV patients who underwent splenic embolization were randomly divided into treatment group and control group (32 cases in each group).Control group was given subcutaneous injection of recombinant human interferon α-2b (rhIFN α-2b) every other day,and oral administration of ribavarin 300 mg three times a day;Treatment group did not only receive the treatment above,but also received subcutaneous injection pegylated interferon α-2a 180 μg once a week.Both groups were treated for 12 weeks.HCV RNA positive rate,blood routine parameters,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) levels,and adverse drug reactions were compared between the two groups.Results Before treatment,HCV RNA positive rate of the two groups were both 100％ (32/32 cases),after treatment,HCV RNA positive rate of treatment group was 53.13％ (17/32 cases) and that of and the control group was 78.12％ (25/32 cases),the difference was statistically significant (P ＜ 0.05).Mter treatment,the ANC of treatment group was (4.76 ± 0.33) × 109/L and that of the control group was (3.92 ±0.17) × 109/L,PLT levels of treatment group was (142.73 ± 17.04) × 109/L and that of and the control group was (128.72 ± 17.96) × 109/L,WBC levels of treatment group was (8.15 ± 1.84) × 109/L and that of and the control group was (6.57 ± 1.69 × 10)9/L,and the difference was statistically significant (P ＜ 0.05).After treatment,the ALT of the experimental group was 41.2 ± 22.4U · L-1 and that of and the control group was (60.1 ± 21.9) U · L-1,AST levels of the experimental group was 33.67 ± 18.46 U · L-1 and that of and the control group was (51.22 ± 16.95) U · L-1;The AST/ALT values were 0.78 ± 0.69,1.27 ± 0.73 in treatment group and in the control group,and the difference was statistically significant (P ＜ 0.05).Adverse drug reactions in treatment group was 40.63％ (13/32 cases),while it was 28.12％ (9/32 cases) in control group,thedifference was not statistically significant (P ＞ 0.05).Conclusion PEG-IFN-α-2a combined with riba virin could not only reduce HCV RNA positive rates,but also improve the serum AST and ALT levels in the treatment of hepatitis C virus-related cirrhosis underwent splenic embolization,which is safe.

OBJECTIVETo observe the anti-virus effects of andrographolide (AD) on the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway when immunological cells were infected with H1N1.

METHODSLeukomonocyte was obtained from umbilical cord blood by Ficoll density gradient centrifugation, and immunological cells were harvested after cytokines stimulation. Virus infected cell model was established by H1N1 co-cultured with normal human bronchial epithelial cell line (16HBE). The optimal concentration of AD was defined by methyl-thiazolyl-tetrazolium (MTT) assay. After the virus infected cell model was established, AD was added into the medium as a treatment intervention. After 24-h co-culture, cell supernatant was collected for interferon gamma (IFN-γ) and interleukin-4 (IL-4) enzyme-linked immunosorbent assay (ELISA) detection while immunological cells for real-time polymerase chain reaction (RT-PCR).

RESULTSThe optimal concentration of AD for anti-virus effect was 250 μg/mL. IL-4 and IFN-γ in the supernatant and mRNA levels in RLRs pathway increased when cells was infected by virus, RIG-I, IFN-β promoter stimulator-1 (IPS-1), interferon regulatory factor (IRF)-7, IRF-3 and nuclear transcription factor κB (NF-κB) mRNA levels increased significantly (P<0.05). When AD was added into co-culture medium, the levels of IL-4 and IFN-γ were lower than those in the non-interference groups and the mRNA expression levels decreased, RIG-I, IPS-1, IRF-7, IRF-3 and NF-κB decreased significantly in each group with significant statistic differences (P<0.05).

CONCLUSIONSThe RLRs mediated viral recognition provided a potential molecular target for acute viral infections and andrographolide could ameliorate H1N1 virus-induced cell mortality. And the antiviral effects might be related to its inhibition of viral-induced activation of the RLRs signaling pathway.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Antiviral Agents ; pharmacology ; Cells, Cultured ; Coculture Techniques ; DEAD Box Protein 58 ; DEAD-box RNA Helicases ; genetics ; metabolism ; Dendritic Cells ; drug effects ; immunology ; virology ; Diterpenes ; pharmacology ; Fetal Blood ; cytology ; Humans ; Influenza A Virus, H1N1 Subtype ; drug effects ; immunology ; Influenza, Human ; drug therapy ; immunology ; virology ; Interferon-beta ; genetics ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Leukocytes, Mononuclear ; drug effects ; immunology ; virology ; Macrophages ; drug effects ; virology ; NF-kappa B ; genetics ; metabolism ; Promoter Regions, Genetic ; drug effects ; immunology ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; genetics ; immunology

Objective To learn the status of human resources of vaccination clinics in Zhejiang province and to give suggestions for optimizing the allocation.Methods Investigation and the focus group interview were conducted in Zhejiang Province to learn the configuration standards in vaccination clinics.Results The mean number who attended the immunization work every vaccination day in those clinics was five.The number of staff in each clinic differed from county to county but all reached 0.9 persons serving for 10,000 residents.There should not be less than four persons in each vaccination clinic theoretically.It should be necessary to increase one vaccination staff in every 50 injection doses of vaccine workload.Conclusion The staff of vaccination clinics is inadequate and unbalanced in Zhejiang Province.We should increase staff numbers according to workload and served population.

OBJECTIVETo assess the relationship of high altitude de-adaptation response (HADAR) with acute high altitude response (AHAR) and cardiac function.

METHODSNinety-six military personnel of rapid entering into high altitude (3 700 to 4 800 m) with strong physical work were analyzed, all subjects were male, aged 18 - 35 years. According to the symptomatic scores of AHAR were divided into 3 groups: sever AHAR (group A, 24), mild to moderate AHAR (group B, 47) and non-AHAR (group C, 25) at high altitude. According to the symptomatic scores of HADAR were divided into 3 groups: severe HADAR (group E, 19), mild to moderate HADAR (group F, 40) and non-HADAR (group G, 37) after return to lower altitude (1 500 m). Mean pulmonary arterial pressure (mPAP), right ventricular internal dimension (RVID), outflow tract of right ventricle (RVOT), left ventricular internal dimension (LVID), left ventricular ejection fraction (LVEF), cardiac muscle work index (Tei index), creatine kinase isoenzymes-MB (CK-MB), lactic dehydrogenase isoenzyme-1 (LDH-1) were measured at high altitude stayed 50 days and after return to lower altitude 12 h, 15 d, and 30 d. Fifty healthy volunteers (group D) at 1 500 m altitude served as control.

RESULTSLevel of mPAP, RVID, RVOT, RVID/LVID ratio, Tei index, CK-MB,and LDH-1 were higher, and LVEF was lower in group A than those in group B, C and D, there were significant differences between group B and C, C and D (all P < 0.01). AHAR scores were positively correlated with HADAR scores (r = 0.863, P < 0.01). Twelve hours after return to lower altitude, level of mPAP, RVID, RVOT, RVI/LVID ratio, Tei index, CK-MB, and LDH-1 were higher, and LVEF was lower in group E than those in group F, G and D, there were significant differences between group F and G, G and D (all P < 0.01). Fifteen days after return to lower altitude, level of mPAP, RVID, RVOT, RVID/LVID ratio were higher in group E than those in group F, G, and D, there were significant differences between group F and G, and D (P < 0.01 or P < 0.05), there were no significant differences between group G and D (all P > 0.05), LVEF, Tei index, CK-MB, LDH-1 showed no significant differences among groups (all P > 0.05). Thirty days after return to lower altitude, these parameters in group E, F, and G showed no significantly differences compared with those of group D (all P > 0.05).

CONCLUSIONThe severity of HADAR is associated with severity of AHAR and cardiac injury, the more serious of AHAR and cardiac injury at high altitude, the more serious of HADAR and cardiac injury after return to lower altitude, the more long of restore of right cardiac morphologic injury.

Adaptation, Physiological ; Adolescent ; Adult ; Altitude ; Altitude Sickness ; metabolism ; physiopathology ; Case-Control Studies ; Heart ; physiopathology ; Heart Function Tests ; Humans ; Male ; Myocardium ; enzymology ; Young Adult