Molecular mechanism of the effect of Gegen Qinlian decoction on COVID-19 comorbid with diabetes mellitus based on network pharmacology and molecular docking: A review.

To explore the potential mechanism of Gegen Qinlian decoction (GGQL) in the treatment of COVID-19 comorbid with diabetes mellitus (DM) through network pharmacology and molecular docking, and to provide theoretical guidance for clinical transformation research. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen the active compounds and targets of GGQL, the targets of COVID-19 comorbid with DM were searched based on Genecards database. Protein-protein interaction network was constructed using String data platform for the intersection of compounds and disease targets, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the intersection targets was performed using DAVID database. Cytoscape software was used to construct the "compound target-pathway (C-T-P)" of GGQL in the treatment of COVID-19 comorbid with DM, the molecular docking platform was used to complete the simulated docking of key compounds and targets. We obtained 141 compounds from GGQL, revealed 127 bioactive compounds and 283 potential targets of GGQL. Quercetin, kaempferol and formononetin in GGQL play a role by modulating the targets (including AR, GSK3B, DPP4, F2, and NOS3). GGQL might affect diverse signaling pathways related to the pathogenesis of coronavirus disease - COVID-19, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, human cytomegalovirus infection and Th17 cell differentiation. Meanwhile, molecular docking showed that the selected GGQL core active components had strong binding activity with the key targets. This study revealed that GGQL play a role in the treatment of COVID-19 comorbid with DM through multi-component, multi-target and multi-pathway mode of action, which provided good theoretical basis for further verification research.

Analyzing the electron trajectories in strong-field tunneling ionization with the phase-of-the-phase spectroscopy.

By numerically solving the time-dependent Schrödinger equation, we theoretically study strong-field tunneling ionization of Ar atom in the parallel two-color field which consists of a strong fundamental pulse and a much weaker second harmonic component. Based on the quantum orbits concept, we analyzed the photoelectron momentum distributions with the phase-of-the-phase spectroscopy, and the relative contributions of the two parts of the photoelectrons produced during the rising and falling edges of the adjacent quarters of the laser cycle are identified successfully. Our results show that the relative contributions of these two parts depend on both of the transverse and longitude momenta. By comparing the results from model atoms with Coulomb potential and short-range potential, the role of the long-range Coulomb interaction on the relative contributions of these two parts of electrons is revealed. Additionally, we show that the effects of Coulomb interaction on ionization time are vital for identifying their relative contributions.

Intensity-dependent angular distribution of low-energy electrons generated by intense high-frequency laser pulse.

By solving the three-dimensional time-dependent Schrödinger equation, we investigate the angular distributions of the low-energy electrons when an intense high-frequency laser pulse is applied to the hydrogen atom. Our numerical results show that the angular distributions of the low-energy electrons which generated by the nonadiabatic transitions sensitively depend on the laser intensity. The angular distributions evolve from a two-lobe to a four-lobe structure as the laser intensity increases. By analyzing nonadiabatic process in the Kramers-Henneberger frame, we illustrate that this phenomenon is attributed to the intensity-dependent adiabatic evolution of the ground state wavefunction. When the laser intensity further increases, the pathway of nonadiabatic transition from the ground state to the excited state and then to the continuum states is non-negligible, which results in the ring-like structure in the photoelectron momentum distribution. The angular distributions of the low-energy electrons provide a way to monitor the evolution of the electron wavefunction in the intense high frequency laser fields.

Low-energy photoelectron interference structure in attosecond streaking.

By numerically solving the time-dependent Schrödinger equation, we theoretically investigate the dynamics of the low-energy photoelectrons ionized by a single attosecond pulse in the presence of an infrared laser field. The obtained photoelectron momentum distributions exhibit complicated interference structures. With the semiclassical model, the originations for the different types of the interference structures are unambiguously identified. Moreover, by changing the time delay between the attosecond pulse and the infrared laser field, these interferences could be selectively enhanced or suppressed. This enables us to extract information about the ionization dynamics encoded in the interference structures. As an example, we show that the phase of the electron wave-packets ionized by the linearly and circularly polarized attosecond pulses can be extracted from the interference structures of the direct and the near-forward rescattering electrons.

Two-dimensional photoelectron holography in strong-field tunneling ionization by counter rotating two-color circularly polarized laser pulses.

Strong-field photoelectron holography (SFPH), originating from the interference of the direct electron and the rescattering electron in tunneling ionization, is a significant tool for probing structure and electronic dynamics in molecules. We theoretically study SFPH by counter rotating two-color circularly (CRTC) polarized laser pulses. Different from the case of the linearly polarized laser field, where the holographic structure in the photoelectron momentum distribution (PEMD) is clustered around the laser polarization direction, in the CRTC laser fields, the tunneling ionized electrons could recollide with the parent ion from different angles and thus the photoelectron hologram appears in the whole plane of laser polarization. This property enables structural information delivered by the electrons scattering the molecule from different angles to be recorded in the two-dimensional photoelectron hologram. Moreover, the electrons tunneling at different laser cycles are streaked to different angles in the two-dimensional polarization plane. This property enables us to probe the sub-cycle electronic dynamics in molecules over a long time window with the multiple-cycle CRTC laser pulses.

Frustrated tunneling ionization in the elliptically polarized strong laser fields.

We theoretically investigated frustrated tunneling ionization (FTI) in the interaction of atoms with elliptically polarized laser pulses by a semiclassical ensemble model. Our results show that the yield of frustrated tunneling ionization events exhibits an anomalous behavior which maximizes at the nonzero ellipticity. By tracing back the initial tunneling coordinates, we show that this anomalous behavior is due to the fact that the initial transverse velocity at tunneling of the FTI events is nonzero in the linear laser pulses and it moves across zero as the ellipticity increases. The FTI yield maximizes at the ellipticity when the initial transverse momentum for being trapped is zero. Moreover, the angular momentum distribution of the FTI events and its ellipticity dependence are also explored. The anomalous behavior revealed in our work is very similar to the previously observed ellipticity dependence of the near- and below-threshold harmonics, and thus our work may uncover the mechanism of the below-threshold harmonics which is still a controversial issue.

Determination of the Ionization Time Using Attosecond Photoelectron Interferometry.

Laser-induced electron tunneling ionization from atoms and molecules plays as the trigger for a broad class of interesting strong-field phenomena in attosecond community. Understanding the time of electron tunneling ionization is vital to achieving the ultimate accuracy in attosecond metrology. We propose a novel attosecond photoelectron interferometer, which is based on the interference of the direct and near-forward rescattering electron wave packets, to determine the time information characterizing the tunneling process. Adding a weak perturbation in orthogonal to the strong fundamental field, the phases of the direct and the near-forward rescattering electron wave packets are modified, leading to the shift of the interferogram in the photoelectron momentum distributions. By analyzing the response of the interferogram to the perturbation, the real part of the ionization time, which denotes the instant when the electron exits the potential barrier, and the associated rescattering time are precisely retrieved. Moreover, the imaginary part of the ionization time, which has been interpreted as a quantity related to electron motion under the potential barrier, is also unambiguously determined.

The effects of recombinant human granulocyte colony-stimulating factor mouthwash on radiotherapy-induced oral mucositis in locally advanced nasopharyngeal carcinoma patients.

BACKGROUND: Acute oral mucositis is a common complication of radiotherapy for nasopharyngeal carcinoma (NPC) patients. OBJECTIVES: The aim of the study was to observe the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on radiotherapy-induced oral mucositis in locally advanced NPC patients. MATERIAL AND METHODS: The study involved 64 locally advanced NPC patients that were randomly allocated to receive either rhG-CSF mouthwash (2 µg/mL rhG-CSF; group A, n = 34) or a compounded mouth rinse (10 µg/mL vitamin B12, 0.48 mg/mL gentamicin and 0.04 mg/mL dexamethasone in saline; group B, n = 30) during radiotherapy. Both mouthwashes were used 6 times daily at the onset of oral mucositis, and the treatments continued until the end of all intensity-modulated radiotherapy sessions. Oral mucositis was graded according to the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria. A visual analog scale was used to assess peak mouth pain once a week, and the duration of oral mucositis was recorded. RESULTS: In comparison with group B, the patients in group A had a significantly lower incidence of oral mucositis of grade 3 or above (38.2% vs 66.7%, p < 0.05) and less peak mucosal pain in the 5th, 6th and 7th weeks of radiotherapy (p < 0.05). group A patients also had shorter durations of oral mucositis (35.1 days vs 39.4 days, p < 0.05) and lower peak swallowing function scores (p < 0.05). CONCLUSIONS: The rhG-CSF mouthwash may be more effective than the compounded mouth rinse in preventing and treating radiotherapy-induced mucositis and mucositis-related pain, and thus improving the quality of life for locally advanced NPC patients. These effects should be further investigated in a prospective controlled study.

Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells.

Hypoxia induces proliferation and invasion in cancer cells via hypoxia-inducible factor (HIF)-1α. The cell adhesion molecule cluster of differentiation (CD) 44 has been associated with increased cell invasion and metastasis. Whether hypoxia regulates the expression of CD44 in gastric cancer cells remains to be established. In the current study, the effects of hypoxia on HIF-1α and CD44 expression levels in human gastric cell lines SGC-7901 and BGC-823 were evaluated. The cells were cultured in 1% O2 for 1 week and then treated with 20 nM rapamycin for 72 h. Cell viability was evaluated using the Cell Counting kit-8 assay, and cell invasion was detected by the Transwell invasion assay. The protein and messenger (m) RNA expression levels of HIF-1α and CD44 were detected using western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The results revealed that cell viability and invasion increased under hypoxic conditions, but decreased following rapamycin treatment in SGC-7901 and BGC-823 cells. Hypoxia also increased the protein and mRNA expression levels of HIF-1α and CD44 in these two cell lines. However, this hypoxia-induced increase in HIF-1α and CD44 protein and mRNA expression levels was inhibited by rapamycin. These findings suggest that hypoxia induced the proliferation and invasion of SGC-7901 and BGC-823 cells. Furthermore, CD44 expression levels were potentially associated with HIF-1α expression levels. Therefore, in gastric cancer cells, hypoxia may regulate CD44 expression via HIF-1α in order to promote cell proliferation and invasion.

S-1 plus gemcitabine chemotherapy followed by concurrent radiotherapy and maintenance therapy with S-1 for unresectable pancreatic cancer.

AIM: To investigate the feasibility and efficacy of the combination of S-1 with gemcitabine followed by oral S-1 with concurrent radiotherapy (intensity modulated radiotherapy, IMRT) and maintenance therapy with S-1 for locally advanced pancreatic cancer. METHODS: Subjects selected in the study were patients who had unresectable and locally advanced pancreatic cancer without distant metastases, adequate organ and marrow functions, an Eastern Cooperative Oncology Group performance status of 0-1 and no prior anticancer therapy. Initially the subjects received two cycles of chemotherapy, oral administration of S-1 40 mg/m(2) twice daily from day 1 to day 14 of a 21-d cycle, with 30-min intravenous infusions of gemcitabine 1000 mg/m(2) on day 1 and day 8. Two weeks after the completion of chemotherapy, S-1 was administered orally with concurrent IMRT. Oral S-1 was administered at a dose of 80 mg/m(2) per day twice daily from day 1 to day 14 and from day 22 to day 35. Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d, 5 times per week, 28 fractions). One month after the completion of chemotherapy and radiotherapy, S-1 was administered orally at a dose of 80 mg/m(2) per day twice daily for 14 d, followed by a 14-d rest period. This cycle was repeated as maintenance therapy, until unacceptable toxicity occurred or the disease worsened. Thirty-two patients were involved in this study. The median follow-up was 15.6 mo (range: 8.6-32.3 mo). RESULTS: Thirty-two patients completed the scheduled course of chemotherapy, while 30 patients (93.8%) received chemoradiotherapy with two patients ceasing to continue with radiotherapy. The major toxic effects were nausea and leukopenia. There was no grade 4 toxicity or treatment-related death. According to the Response Evaluation Criteria in Solid Tumors criteria, the objective tumor response was partial response in 17 (53.1%) patients, stable disease in 9 (28.1%), and progressive disease in 6 (18.8%). The median overall survival and median progression-free survival were 15.2 mo and 9.3 mo, respectively. The survival rates at 1 year and 2 years were 75% and 34.4%, respectively. CONCLUSION: The combination of S-1 with gemcitabine followed by oral S-1 with IMRT and maintenance therapy with S-1 alone in patients with locally advanced pancreatic cancer may be considered a well-tolerated, promising treatment regimen.

Early efficacy of Endostar combined with chemoradiotherapy for advanced cervical cancers.

The aim of this study was to investigate the early outcome of Endostar combined with chemoradiotherapy for advanced cervical cancer. Fifty-two cases (FIGO IIb to IVa) were divided randomly into two groups, receiving chemoradiotherapy alone (CRT group) and Endostar combined with chemoradiotherapy (CRT+E group). For the patients in the CRT+E group, Endostar was administered daily with the dosage of 7.5 mg/m2, and cisplatin was administered weekly with the dosage of 20 mg/m2 during the radiation. The regimens lasted for 4 weeks with no difference in chemoradiotherapy between the two groups. The early outcome complete remission rate was 73.1%, partial remission rate was 23.1% and the total response rate was 96.2% in CRT+E group, a significnat improvement on the 34.6%, 42.3% and 76.9%, respectively, in the CRT group. One year survive rates were 100% and 84.6% in the CRT+E group and CRT groups, the difference being significant. Endostar combined with chemoradiotherapy can improve the early outcome of the advanced cervical cancer, and adverse effects were not encountered.

Early efficacy of taxotere and cisplatin chemo-radiotherapy for advanced cervical cancer.

The aim of this study was to investigate the early outcome of the taxotere and cisplatin chemoradiotherapy to the advanced cervical cancer. Fifty-six cases with cervical cancer (FIGO II b to IVa) were divided randomly into two groups: radiotherapy alone (28 cases) and radiation plus chemotherapy (TP) group. There was no difference of radiotherapy between the two groups. The RT+C cases who received TP regimen during the radiation, and DDP once weekly injection of vain, according to 20 mg/m2 and taxotere once weekly i.v. according to 35 mg/m2.These regimen were given for 4~5 weeks, and some medicine for vomiting was given to the RT+C cases. Two groups were received an oral medicine MA 160 mg every day during the treatment. The early outcome: the complete remission rate was 64.3% and partial remission rate was 35.7% in RT+C. the complete remission rate was 32.1% and partial remission rate was 39.3% in RT. The total response rate and complete remission of RT+C group was higher than that of the RT group. There was significant difference between the two groups. The taxotere and cisplatin chemoradiotherapy can improve the early outcome of the advanced cervical cancer, the adverse effects being endurable.

[Analysis of the initial efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer].

OBJECTIVE: To investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer. METHODS: Forty-two cases of cervical cancer (FIGO IIb to IVa) were divided randomly into two groups: radiotherapy alone (21 cases) and radiation plus chemotherapy (Nedaplatin) group. The same radiotherapy was given to the two groups. Patients of the RT + C group received nedaplatin 30 mg/m2 in intravenous drip infusion once weekly on day 1, for 4 to 5 weeks, and megestrol 160 mg orally every day during the radiation therapy. RESULTS: The early outcome: the complete remission rate was 81.0% and partial remission rate was 19.0% in the RT + C group, significantly better than the CR (38.1%) and PR (42.9%) in the RT group. The 1-year survival rates in the two groups were 100% (21/21) and 81.0% (17/21), respectively, with a significant difference between the two groups (P<0.05). CONCLUSIONS: The combination of nedaplatin and megestrol with concurrent chemoradiotherapy can improve the early outcome of advanced cervical cancer, with somewhat increased but tolerable adverse effects.