Online medical consultation in China: Evidence from obesity doctors.

Objective: Online medical consultation (OMC) is increasingly used in China, but there have been few in-depth studies of consultation arrangements and fee structures of online doctors in China. This research assessed the consultation arrangements and fee structure of OMC in China by undertaking a case study of obesity doctors from four representative OMC platforms. Methods: Detailed information, including fees, waiting time and doctor information, was collected from four obesity OMC platforms and analyzed using descriptive statistical analysis. Results: The obesity OMC platforms in China shared similarities in the use of big data and artificial intelligence (AI) but differed across service access, specific consultation arrangements and fees. Big data search and AI response technologies were used by most platforms to match users with doctors and reduce doctors' pressure. The descriptive statistical analysis showed that the higher the rank of the online doctor, the higher the online fee and the longer the wait time. Through a comparison with offline hospitals, we found online doctors' fees exceeded offline hospital doctors' fees by up to 90%. Conclusions: OMC platforms can gain competitive advantages over offline medical institutions through the following measures: make fuller use of big data and AI technologies to provide users with longer duration, lower cost and more efficient consultation services; provide better user experience than offline medical institutions; use big data and fee advantages to screen doctors to match users' consultation needs instead of screening by the rank of doctors only; and cooperate with commercial insurance providers to provide innovative health care packages.

Comparison of different thread products for facial rejuvenation: Materials and barb designs.

BACKGROUND: In recent years, the thread-lifting technique has become widely used in clinical settings. Several thread products are used in clinical practice, and there are many differences between products in terms of many aspects. METHODS: Six commercial thread products were collected and evaluated. The general structure, microstructure, elastic modulus, and strength were evaluated using microscopies and tensile testing in vitro. Seventy-two female rats were divided into six groups. Tissue samples were harvested and histologically evaluated at 1st, 4th, 8th, and 12th week using hematoxylin and eosin and Masson's trichrome staining. RESULTS: There were differences between products in terms of barb shape, microstructure, elasticity, and strength, and that could be attributed to the materials and barb structures. All threads showed good biological safety, and the density of collagen area in the dermis was increased compared to that in the control group. CONCLUSIONS: This study provided an objective evaluation of barbed thread products, which indicated that all products can be used safely with certain effects in different indications.

Scalable Alkaline Zinc-Iron/Nickel Hybrid Flow Battery with Energy Density up to 200 Wh L-1.

Achieving net-zero emissions requires low-cost and reliable energy storage devices that are essential to deploy renewables. Alkaline zinc-based flow batteries such as alkaline zinc-iron (or nickel) flow batteries are well suited for energy storage because of their high safety, high efficiency, and low cost. Nevertheless, their energy density is limited by the low solubility of ferro/ferricyanide and the limited areal capacity of sintered nickel electrodes. Here, combining the electrochemical reaction with the chemical reaction of ferro/ferricyanide couple in a homemade nickel electrode, an alkaline zinc-iron/nickel hybrid flow battery with a high energy density of 208.9 Wh L-1 and an energy efficiency of 84.7% at a high current density of 80 mA cm-2 is reported. The reversible chemical reactions between dual couples are proven to stabilize the nickel electrode by promoting the activation of the nickel electrode and further preventing the formation of γ-NiOOH. A kW-scale stack is demonstrated by the integration of ferro/ferricyanide couple with nickel electrode, delivering a coulombic efficiency of 98% and an energy efficiency of 89% at 40 mA cm-2 . This work demonstrates a promising pathway for constructing and upscaling flow batteries with high energy density and low cost.

Nationwide Lockdown, Population Density, and Financial Distress Brings Inadequacy to Manage COVID-19: Leading the Services Sector into the Trajectory of Global Depression.

The service industry provides distributive services, producer services, personal services, and social services. These services largely breakdowns due to restrictions on border movements, confined travel and transportation services, a decline in international tourists' visitation, nationwide lockdowns, and maintaining social distancing in the population. Although these measures are highly needed to contain coronavirus, it decreases economic and financial activities in a country, which requires smart solutions to globally subsidize the services sector. The study used different COVID-19 measures, and its resulting impact on the services industry by using world aggregated data from 1975 through 2020. The study benefited from the Keynesian theory of aggregate demand that remains provided a solution to minimize economic shocks through stringent or liberalizing economic policies. The COVID-19 pandemic is more severe than the financial shocks of 2018 that affected almost all sectors of the globalized world, particularly the services sector, which has been severally affected by COVID-19; it is a high time to revisit economic policies to control pandemic recession. The study used quantiles regression and innovation accounting matrix to obtain ex-ante and ex-post analysis. The quantile regression estimates show that causes of death by communicable diseases, including COVID-19, mainly decline the share of services value added to the global GDP at different quantiles distribution. In contrast, word-of-mouth helps to prevent it from the transmission channel of coronavirus plague through information sharing among the general masses. The control of food prices and managing physical distancing reduces suspected coronavirus cases; however, it negatively affects the services sector's value share. The smart lockdown and sound economic activities do not decrease coronavirus cases, while they support increasing the percentage of the services sector to the global GDP. The innovation accounting matrix suggested that smart lockdown, managing physical distancing, effective price control, and sound financial activities will help to reduce coronavirus cases that will further translate into increased services value-added for the next ten years. The social distancing will exert a more considerable variance error shock to the services industry, which indicates the viability of these measures to contained novel coronavirus over a time horizon. The study used the number of proxies to the COVID-19 measures on the service sector that can be continued with real-time variables to obtain more inferences.

Quantifiable clinical efficacy of injectable porcine collagen for the treatment of structural dark circles.

BACKGROUND: Dark circles are one of the most perplexing cosmetic problems for modern people. Nowadays, a new porcine collagen filler has been popular in China and many countries and has high safety. AIMS: The purpose of this study is to explore and quantify the efficacy of this collagen filler in treating structured dark circles objectively and systematically. METHODS: This is a prospective study. Twenty patients were included and took standard facial photographs at preoperative (Tp), immediately postoperative (T0), 1 week (T1), 2 weeks (T2), 4 weeks (T4), 8 weeks (T8), and 12 weeks (T12). The efficacy was quantified by measuring the depression of the tear trough and infraorbital melanin content. Three dermatologists blinded to the treatment were responsible for completing the subjective evaluations. RESULTS: The depression volume, depression-affected area, and depression maximum depth of the tear trough decreased significantly immediately postoperation, and then all values increased slowly with time (P <.05). After 3-month observation, we found that the residual effect of the treatment is 45.08% ± 15.53% (T8) and 17.37% ± 16.79% (T12). The melanin contents at the medial point (A), the middle point (B), and the lateral point (C) all decreased instantly after injection (A: 8.23% ± 5.07%, B: 6.29% ± 5.05%, C: 5.11% ± 5.44% ), which suggested that collagen filler had an instant covering effect for structural dark circles. Patients showed only slight redness and swelling after the treatment. CONCLUSION: Collagen filler is a very effective treatment method for structural dark circles. Besides, it may also have a certain therapeutic effect on the other three dark circles types.

The Aesthetic Concerns of Botulinum Toxin Type A in the Treatment of Neck Wrinkles: A Systematic Review.

BACKGROUND: The aged and unattractive appearance of the neck has a profound impact on the overall youthfulness and attractiveness of the face. Neck wrinkles are one of the manifestations of neck skin aging. Botulinum toxin type A (BTX-A) represents an effective means for aesthetic neck rejuvenation as novel facial rejuvenation technologies are progressively developed. OBJECTIVES: The objective of this article was to review the pertinent clinical literature for descriptions of BTX-A treatments and evaluations of their efficacy and safety for neck wrinkles. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library, and SCOPUS databases were searched from inception to April 30, 2020, for the existing literature, which is presented along with the authors' experience with neck wrinkles. RESULTS: Overall, 112 women between 24 and 65 years of age were included in 3 studies of monotherapy and 2 studies of multimodal combination therapy. BTX-A has been reported in combination with other approaches, including intensity focused ultrasound, cohesive polydensified matrix hyaluronic acid, and microfocused ultrasound. Only 1 of the 3 reports on monotherapy had a less than 50% satisfaction and improvement rate. Overall, BTX-A attained high patient satisfaction without serious and persistent side effects, notwithstanding the relatively limited sample size. CONCLUSIONS: The existing research cannot strongly prove the aesthetic effect of BTX-A in neck wrinkles. However, BTX-A is probably an effective technology in response to the growing demand for neck wrinkle treatment, whether in a single treatment or combined treatment.

Marker residue determination of tritium-labeled ivermectin in the muscle of aquacultured largemouth bass, hybrid striped bass, and yellow perch following oral treatment.

The residue depletion profiles of tritium-labeled ivermectin and its metabolites in the muscle of aquacultured largemouth bass (LMB), hybrid striped bass (HSB), and yellow perch (YP) following oral treatment are reported. Fish were administered ³H-ivermectin at the dose level of 0.1 mg/kg body weight (7-9 µCi) in a gel capsule via stomach tube. At each postdose withdrawal time, six fish of each species were sedated with buffered MS-222 and blood samples taken. Fish were then euthanized, and fillets with adhering skin (scales removed) and bile samples were collected. The muscle fillets were homogenized in dry ice to a fine powder. Aliquots of tissue, plasma, and bile were assayed for total radioactive residue (TRR). The homogenized muscle was extracted in acetonitrile or methanol followed by high-performance liquid chromatographic (HPLC) analysis to determine the presence of parent ivermectin and its potential metabolites. The highest TRR concentrations (ivermectin equivalents) of 53, 45, and 44 ng/g (ppb) were obtained on postdose day 1 for HSB, LMB, and YP, respectively. The TRR depleted most slowly in HSB to 25 ppb at day 91, followed by YP to 19 ppb at day 42 and then by LMB to 22 ppb at day 35. The total residue of ivermectin and its metabolites by HPLC analysis followed the same depletion pattern in the three species. Additionally, the depletion rate of TRR of ³H-ivermectin in the three species followed the pattern bile > plasma > muscle. The results further indicate that one of the polar metabolites of ivermectin could serve as a potential marker residue as an indication of use, rather than the parent ivermectin.

Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 µM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 µM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.

Development of a method to determine albendazole and its metabolites in the muscle tissue of yellow perch using high-performance liquid chromatography with fluorescence detection.

An HPLC method was developed for the determination of albendazole (ABZ) and its metabolites, a sulfoxide (ABZSO), a sulfone (ABZSO2), and albendazole-2-aminosulfone (ABZ-2-NH2SO2), from yellow perch muscle tissue with adhering skin. The muscle tissue samples were made alkaline with potassium carbonate and extracted with ethyl acetate, followed by a series of liquid-liquid extraction steps. After solvent evaporation, the residue was reconstituted in the initial mobile phase combination of the gradient. The mobile phase consisted of a buffer, 50 mM ammonium acetate (pH = 4.0) in 10% methanol-water, and 100% acetonitrile. The gradient was from 20% acetonitrile to 85% acetonitrile. The analytes were chromatographed on an RP Luna C18(2) column and detected by fluorescence with excitation and emission wavelengths of 290 and 330 nm, respectively. The average recoveries from fortified muscle tissue for ABZ (20-100 ppb), ABZ-SO (20-200 ppb), ABZSO2 (8-100 ppb), and ABZ-2-NH2SO2 (20-100 ppb) were 85, 95, 101, and 86%, respectively, with corresponding CV values of 9, 3, 6, and 4%, respectively. Their LOQ values were 10, 10, 1, and 10 ppb, respectively. The procedure was applied to determine ABZ and its major metabolites in the incurred muscle tissue of yellow perch obtained after orally dosing the fish with ABZ.

Anti-AIDS agents 84. Synthesis and anti-human immunodeficiency virus (HIV) activity of 2'-monomethyl-4-methyl- and 1'-thia-4-methyl-(3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.

In a continuing investigation into the pharmacophores and structure-activity relationship (SAR) of (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) as a potent anti-HIV agent, 2'-monomethyl substituted 1'-oxa, 1'-thia, 1'-sulfoxide, and 1'-sulfone analogs were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Among them, 2'S-monomethyl-4-methyl DCK (5a)(‡) and 2'S-monomethyl-1'-thia-4-methyl DCK (7a) exhibited potent anti-HIV activity with EC(50) values of 40.2 and 39.1 nM and remarkable therapeutic indexes of 705 and 1000, respectively, which were better than those of the lead compound DCK in the same assay. In contrast, the corresponding isomeric 2'R-monomethyl-4-methyl DCK (6) and 2'R-monomethyl-1'-thia-4-methyl DCK (8) showed much weaker inhibitory activity against HIV-1 replication. Therefore, the bioassay results suggest that the spatial orientation of the 2'-methyl group in DCK analogs can have important effects on anti-HIV activity of this compound class.

Anti-AIDS agents 82: synthesis of seco-(3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents.

Thirteen novel seco-DCK analogs (4-16) with several new skeletons were designed, synthesized and screened for in vitro anti-HIV-1 activity. Among them, three compounds (5, 13, and 16) showed moderate activity, and compound 9 exhibited the best activity with an EC(50) value of 0.058 microM and a therapeutic index (TI) of 1000. The activity of 9 was better than that of 4-methyl DCK (2, EC(50): 0.126 microM, TI: 301.2) in the same assay. Additionally, 9 also showed antiviral activity against a multi-RT inhibitor-resistant strain (RTMDR), which is insensitive to most DCK analogs. Compared with 2, compound 9 has a less complex structure, fewer hydrogen-bond acceptors, and a reduced log P value. Therefore, it is likely to exhibit better ADME, and appears to be a promising new lead for further development as an anti-HIV candidate.

Antitumor agents. 272. Structure-activity relationships and in vivo selective anti-breast cancer activity of novel neo-tanshinlactone analogues.

Neo-tanshinlactone (1) and its previously reported analogues, such as 2, are potent and selective in vitro antibreast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, with a better overall yield. Structure-activity relationships studies on these compounds revealed some key molecular determinants for this family of antibreast agents. Several derivatives (19-21 and 24) exerted potent and selective antibreast cancer activity with IC(50) values of 0.3, 0.2, 0.1, and 0.1 microg/mL, respectively, against the ZR-75-1 cell lines. Compound 24 was 2- to 3-fold more potent than 1 against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analogue 2 showed potent activity against a ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19-21 and 24 as clinical trial candidates is warranted.

Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents.

In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA analogues were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC(50) = 0.09 microM) when compared to HIV entry inhibitors 3b (IC9564, (3R,4S)-N'-[N-[3beta-hydroxy-lup-20(29)-en-28-oyl]-8-aminooctanoyl]-4-amino-3-hydroxy-6-methylheptanoic acid) and 4 (A43-D, [[N-[3beta-O-(3',3'-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC(50) values of 0.007 and 0.006 microM, respectively. These results are slightly better than that of bevirimat (2, 3',3'-dimethylsuccinylbetulinic acid), which is currently in phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates.

Cytotoxic phenanthrenequinones and 9,10-dihydrophenanthrenes from Calanthe arisanensis.

Two new phenanthrenequinones, calanquinones B and C (2 and 3) and four new 9,10-dihydrophenanthrenes, calanhydroquinones A-C (4-6) and calanphenanthrene A (7), along with five known compounds (1 and 8-11), were isolated from an EtOAc-soluble extract of Calanthe arisanensis through bioassay-guided fractionation. Their structures were identified from spectroscopic data, and the compounds were tested for in vitro cytotoxic activity against human lung (A549), prostate (PC-3 and DU145), colon (HCT-8), breast (MCF-7), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KBVIN) cancer cell lines. Compound 1 showed the highest potency (EC(50) < 0.5 microg/mL) against all seven cancer cell lines, with the greatest activity against breast cancer MCF-7 cells (EC(50) < 0.02 microg/mL). Generally, except for 7, compounds 2-11 also showed significant cytotoxic activity (EC(50) < 4 microg/mL) against some cell lines (especially PC-3 and MCF-7) in the panel.

Development and preclinical studies of broad-spectrum anti-HIV agent (3'R,4'R)-3-cyanomethyl-4-methyl-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (3-cyanomethyl-4-methyl-DCK).

In prior investigation, we discovered that (3'R,4'R)-3-cyanomethyl-4-methyl-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (4, 3-cyanomethyl-4-methyl-DCK) showed promising anti-HIV activity. In these current studies, we developed and optimized successfully a practical 10-step synthesis for scale-up preparation to increase the overall yield of 4 from 7.8% to 32%. Furthermore, compound 4 exhibited broad-spectrum anti-HIV activity against wild-type and drug-resistant viral infection of CD4+ T cell lines as well as peripheral blood mononuclear cells by both laboratory-adapted and primary HIV-1 isolates with distinct subtypes and tropisms. Compound 4 was further subjected to in vitro and in vivo pharmacokinetic studies. These studies indicated that 4 has moderate cell permeability, moderate oral bioavailability, and low systemic clearance. These results suggest that 4 should be developed as a promising anti-HIV agent for development as a clinical trial candidate.

Cytotoxic calanquinone A from Calanthe arisanensis and its first total synthesis.

Calanquinone A (1) was isolated from an EtOAc-soluble extract of Calanthe arisanensis through bioassay-guided fractionation. Its structure was identified by spectroscopic methods. Compound 1 showed potent cytotoxicity (EC(50)<0.5microg/mL) against lung (A549), prostate (PC-3 and DU145), colon (HCT-8), breast (MCF7), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines, and interestingly, showed an improved drug resistance profile compared to paclitaxel. The total synthesis of 1 was also achieved and is reported herein.

Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives.

This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3microM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC(50) of 0.22microM, which was approximately 100-fold more potent than glycyrrhetinic acid.

Development of amperometric glucose biosensor through immobilizing enzyme in a Pt nanoparticles/mesoporous carbon matrix.

Pt nanoparticles were deposited on mesoporous carbon material CMK-3. Glucose oxidase (GOx) was immobilized in the resulting Pt nanoparticles/mesoporous carbon (Pt/CMK-3) matrix, and then the mixture was cast on a glassy carbon electrode (GCE) using gelatin as a binder. The glucose biosensor exhibited excellent current response to glucose after cross-linking with glutaraldehyde. At 0.6V (vs. SCE) the response current was linear to glucose concentration in the range of 0.04-12.2mM. The response time (time for achieving 95% of the maximum current) was 15s and the detection limit (S/N=3) was 1 microM. The Michaelis-Menten constant (K(m)(app)) and the maximum current density (i(max)) were 10.8 mM and 908 microAcm(-2), respectively. The activation energy of the enzymatic reaction was estimated to be 22.54 kJ mol(-1). The biosensor showed good stability. It achieved the maximum response current at about 52 degrees C and retained 95.1% of its initial response current after being stored for 30 days. In addition, some fabrication and operation parameters for the biosensor were optimized in this work. The biosensor was used to monitor the glucose levels of serum samples after being covered with an extra Nafion film to improve its anti-interferent ability and satisfied results were obtained.

Anti-AIDS agents 73: structure-activity relationship study and asymmetric synthesis of 3-O-monomethylsuccinyl-betulinic acid derivatives.

3-O-3'(or 2')-Methylsuccinyl-betulinic acid (MSB) derivatives were separated by using recycle HPLC. The structures of four isomers were assigned by NMR and asymmetric synthesis. 3-O-3'S-Methylsuccinyl-betulinic acid (3'S-MSB, 4) exhibited potent anti-HIV activity with an EC(50) value of 0.0087microM and a TI value of 6.3x10(3), which is comparable to the data for bevirimat (DSB, PA-457), a current clinical trials drug that was also derived from betulinic acid. The anti-HIV potency of 4 was slightly better than that of AZT.