The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective To investigate the current status of taste disorders in type 2 diabetes mellitus(T2DM)and to explore whether the taste disorders persists after 3 months of novel corona virus(COVID-19)infection.Methods 95 T2DM out patients(23 without COVID-19 infection history,72 infected with COVID-19 3～4 months ago)visiting the Endocrine Department of the Strategic Support Force Medical Center from February 20 to March 10,2023 were collected.Taste test box was used to test the taste function.General information,biochemical indicators,taste disorders,etc.were compared between the two groups.Results The average age of T2DM patients in this group was(58.3±9.6)years old,61 patients were male(64.2%),the median duration of DM was 11 years,and the median HbA1c was 7.3%.In taste testing,the proportion of sour,sweet,bitter,salty taste perception disorders was 60.0%,45.3%,57.9%,41.1%,84.2%.The average number of days from infection to enrollment into COVID-19 group was 102.4 days.The proportion of acid,sweet,bitter and salty sensory disorders was 61.1%,44.4%,55.6%and 41.7%in COVID-19 group and 56.5%,47.8%,65.2%and 39.1%in non-COVID-19 group.The prevalence of taste disorders in COVID-19 group was higher than that in non-COVID-19 group(86.1%vs 78.3%).Conclusions Taste disorders are common in T2DM patients.Compared with uninfected T2DM patients,there is no significant difference in the prevalence of taste disorders 3 months after COVID-19 infection.

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.

ObjectiveTo establish a high performance liquid chromatography（HPLC） fingerprint of Yanghetang benchmark sample， and evaluate its quality with chemometric methods， so as to provide a reference for the quality control of this benchmark sample. MethodHPLC was used to establish the fingerprint of Yanghetang benchmark sample with ZORBAX SB-C₁₈ column（4.6 mm×250 mm， 5 μm）， the mobile phase was consisted of acetonitrile（A） -0.05% phosphoric acid aqueous solution （containing 0.05% triethylamine solution）（B） for gradient elution（0-5 min， 2%-3%A； 5-15 min， 3%-5%A； 15-65 min， 5%-30%A； 65-90 min， 30%-70%A）， the flow rate was 1.0 mL·min^-1， the column temperature was 35 ℃， and the detection wavelength was 210， 260 nm. Traditional Chinese Medicine（TCM） Chromatographic Fingerprint Similarity Evaluation System （2012 edition） combined with cluster analysis， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to evaluate the quality differences between different batches of Yanghetang benchmark samples， and to find the main chemical components responsible for the quality differences. ResultHPLC fingerprint of Yanghetang benchmark sample was established， 13 common peaks were identified and attributed to each common peak， including peaks 2 and 8 from Rehmanniae Radix Praeparata， peaks 10 and 11 from Cinnamomi Cortex， peaks 1， 3-6 from fried Sinapis Semen， peak 13 from Ephedrae Herba， and peaks 7， 9， 12 from Glycyrrhizae Radix et Rhizoma. Eight of them were identified by comparing with control substance， which were 5-hydroxymethylfurfural（peak 2）， sinapine thiocyanate（peak 4）， glycyrrhizin（peak 7）， verbascoside（peak 8）， cinnamic acid（peak 10）， cinnamaldehyde（peak 11）， glycyrrhizic acid（peak 12） and ephedrine hydrochloride（peak 13）. The similarities of the HPLC fingerprints of 15 batches of Yanghetang benchmark samples with the control fingerprint were all greater than 0.80. The three chemometric methods could classify the samples into two categories. Eight differential components were screened out， among which 5-hydroxymethylfurfural， sinapine thiocyanate， verbascoside and ephedrine hydrochloride were identified. ConclusionThe established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition of Yanghetang benchmark sample， and can provide a basis for establishment of quality standards for compound preparations of this famous classical formula.

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

OBJECTIVE To design paclitaxel prodrug nanoparticles with dual reactive oxygen species/glutathione response (ProPTX-SS-NPs), providing new ideas and methods for the application of paclitaxel. METHODS The optimal preparation method and process of prodrug nanoparticles was investigated by using particle size and PDI as indicators; the morphology of prodrug nanoparticles was observed through electron microscopy and their particle size, potential, encapsulation efficiency, drug loading capacity, etc were investigated; the in vitro release characteristics of nanoparticles in reactive oxygen species and glutathione environments were investigated; the in vitro cytotoxicity and cellular uptake of prodrug nanoparticles were investigated through cell experiments. RESULTS The nano particle size prepared by the optimal process was (130.20±2.18)nm, with the PDI of 0.12±0.01, the Zeta potential of (-8.45±0.01)mV, the drug load of (10.27±1.36)%, and the encapsulation rate of (93.22±2.20)%. The prodrug nanoparticles showed reactive oxygen species and glutathione dual responsive release ability, and could significantly inhibit the proliferation of MCF-7, HepG2, and MDA-MB-231. Its inhibitory effect on MDA-MB-231 cells was the most significant. The IC50 of prodrug nanoparticles on MDA-MB-231 cells was (0.71±0.11)μmol·L, while the IC50of PTX was (22.38±3.27)μmol·L. CONCLUSION ProPTX-SS-NPs have excellent tumor microenvironment response performance and significant anti-tumor activity, which is a highly potential and promising anti-tumor nanosystem.

Molar-incisor hypomineralization (MIH) is defined as an enamel mineralization defect caused by systemic factors, which is characterized by demarcated opacities. These opacities are liable to result in brittle hypomineralized enamel breakdown, which expediting the eventual development of cavities, even tooth loss. Early diagnosis and prompt intervention are essential. The MIH scoring system based on the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD) is internationally recognized. This system is particularly helpful to diagnose and evaluate the MIH, as well as conductive to the performance of epidemiological investigations. This paper gives a presentation on the EAPD judgment criteria and scoring system as well as their applications, based on the current situation of MIH studies and our findings of MIH epidemiological investigation.

It is known that low-frequency pulsed electromagnetic fields (PEMFs) can promote the differentiation and maturation of rat calvarial osteoblasts (ROBs) cultured in vitro. However, the mechanism that how ROBs perceive the physical signals of PEMFs and initiate osteogenic differentiation remains unknown. In this study, we investigated the relationship between the promotion of osteogenic differentiation of ROBs by 0.6 mT 50 Hz PEMFs and the presence of polycystin2 (PC2) located on the primary cilia on the surface of ROBs. First, immunofluorescence staining was used to study whether PC2 is located in the primary cilia of ROBs, and then the changes of PC2 protein expression in ROBs upon treatment with PEMFs for different time were detected by Western blotting. Subsequently, we detected the expression of PC2 protein by Western blotting and the effect of PEMFs on the activity of alkaline phosphatase (ALP), as well as the expression of Runx-2, Bmp-2, Col-1 and Osx proteins and genes related to bone formation after pretreating ROBs with amiloride HCl (AMI), a PC2 blocker. Moreover, we detected the expression of genes related to bone formation after inhibiting the expression of PC2 in ROBs using RNA interference. The results showed that PC2 was localized on the primary cilia of ROBs, and PEMFs treatment increased the expression of PC2 protein. When PC2 was blocked by AMI, PEMFs could no longer increase PC2 protein expression and ALP activity, and the promotion effect of PEMFs on osteogenic related protein and gene expression was also offset. After inhibiting the expression of PC2 using RNA interference, PEMFs can no longer increase the expression of genes related to bone formation. The results showed that PC2, located on the surface of primary cilia of osteoblasts, plays an indispensable role in perceiving and transmitting the physical signals from PEMFs, and the promotion of osteogenic differentiation of ROBs by PEMFs depends on the existence of PC2. This study may help to elucidate the mechanism underlying the promotion of bone formation and osteoporosis treatment in low-frequency PEMFs.
Alkaline Phosphatase/metabolism* ; Animals ; Electromagnetic Fields ; Osteoblasts/metabolism* ; Osteogenesis/genetics* ; Rats ; TRPP Cation Channels/physiology*

Objective:To investigate the effect of usage of transthoracic echocardiography(TTE) on the prognosis of patients after acute kidney injury (AKI) in intensive care unit (ICU).Methods:The clinical data of patients with AKI in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ v1.4) database was collected retrospectively, and the patients were divided into TTE group (with TTE within 24 hours of AKI diagnosis) and No-TTE group (without TTE examination or first TTE examination was more than 24 hours after AKI diagnosis). Propensity score matching (PSM) was utilized to balance the baseline variables between the two groups and Cox regression analysis was used to evaluate the independent risk factors for 28-day all-cause mortality (the primary outcome). Moreover, after PSM, the effects of TTE usage on the second outcomes (including the volumes of intravenous fluid and urine output in the first, second and third 24-hour after the diagnosis of AKI; the total number of mechanical ventilation-free days, renal replacement therapy-free days and vasopressor-free days within 28 days after ICU admission; use of diuretics after the diagnosis of AKI; reduction in serum creatinine within 48 hours after the diagnosis of AKI; and the length of ICU stay and hospital stay) were also evaluated.Results:Among 23 945 eligible AKI patients, 3 365 patients (14.1%) patients received TTE within 24 hours after the diagnosis of AKI and finally there were 3 361 patients in TTE group and No-TTE group included in this study after PSM based on the ratio of 1∶1. After PSM, all variables in the two groups were well balanced (standardized mean difference<0.1, respectively). Before and after PSM, patients in TTE group had lower 28-day all-cause mortality compared with patients in No-TTE group (10.76% vs 13.04%, χ2=13.535, P<0.001; 10.65% vs 18.80%, χ2=88.932, P<0.001), and Kaplan-Meier survival curves also revealed that patients in the TTE group had higher cumulative survival rate compared with patients in No-TTE group (Log-rank χ2=15.438, P<0.001; Log-rank χ2=75.360, P<0.001, respectively). Multivariate Cox regression analysis showed that TTE was an independent influencing factor for 28-day all-cause mortality before and after PSM ( HR=0.80, 95% CI 0.73-0.89, P<0.001; HR=0.58, 95% CI 0.51-0.65, P<0.001). And all subgroup analyses showed the similar results. Compared with patients in the No-TTE group, patients in the TTE group had higher volume of intravenous fluid on the first day and the second day after the diagnosis of AKI (both P<0.01). Patients in the TTE group had higher volume of urine output on the first day and the third day after the diagnosis of AKI (both P<0.01). The patients in the TTE group had a significantly lower duration of vasopressor-free and mechanical ventilation-free (both P<0.01). The usage of diuretic was significantly higher in the TTE group compared with that in the No-TTE group (54.1% vs 44.2%, χ2=65.609, P<0.001). With respect to serum creatinine, the reduction in serum creatinine within 48 hours after the diagnosis of AKI was higher in the TTE group than that in the No-TTE group [36.6(23.0, 97.2) μmol/L vs 30.1(14.2, 61.9) μmol/L, Z=-9.549, P<0.001]. Moreover, TTE group had shorter ICU stay than that in the No-TTE group [5.03(3.40, 8.90) d vs 5.37(3.77, 10.00) d, Z=-6.589, P<0.001]. There were no significant difference between the two groups in other secondary outcomes (all P>0.05). Conclusions:Timely TTE utilization after AKI incident is associated with better clinical outcomes for ICU patients.