1.Regulation of kidney on potassium balance and its clinical significance.
Qiong-Hong XIE ; Chuan-Ming HAO
Acta Physiologica Sinica 2023;75(2):216-230
		                        		
		                        			
		                        			Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Bartter Syndrome/metabolism*
		                        			;
		                        		
		                        			Pseudohypoaldosteronism/metabolism*
		                        			;
		                        		
		                        			Potassium/metabolism*
		                        			;
		                        		
		                        			Aldosterone/metabolism*
		                        			;
		                        		
		                        			Hypokalemia/metabolism*
		                        			;
		                        		
		                        			Gitelman Syndrome/metabolism*
		                        			;
		                        		
		                        			Hyperkalemia/metabolism*
		                        			;
		                        		
		                        			Clinical Relevance
		                        			;
		                        		
		                        			Epithelial Sodium Channels/metabolism*
		                        			;
		                        		
		                        			Kidney Tubules, Distal/metabolism*
		                        			;
		                        		
		                        			Sodium/metabolism*
		                        			;
		                        		
		                        			Hypertension
		                        			;
		                        		
		                        			Alkalosis/metabolism*
		                        			;
		                        		
		                        			Water/metabolism*
		                        			;
		                        		
		                        			Kidney/metabolism*
		                        			
		                        		
		                        	
2.Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior.
Xiao-Qing ZHAO ; Dong-Ling LIAO ; Fei-Yu QI ; Zi-Chen LIANG ; Xue-Fang TANG ; Sheng-Yun DAI ; Yan-Jiang QIAO ; Bing XU
China Journal of Chinese Materia Medica 2023;48(12):3180-3189
		                        		
		                        			
		                        			In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
		                        		
		                        		
		                        		
		                        			Commerce
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Tablets
		                        			;
		                        		
		                        			Water
		                        			;
		                        		
		                        			Drug Compounding
		                        			
		                        		
		                        	
3.Study on the sterilization effect of plasma jet and plasma activated water on Streptococcus mutans.
Si QIN ; Running WANG ; Hu LI ; Kaiyuan FAN ; Gang WANG ; Yiyi ZHANG
Journal of Biomedical Engineering 2023;40(3):559-565
		                        		
		                        			
		                        			To explore the effects of plasma jet (PJ) and plasma activated water (PAW) on the sterilization of Streptococcus mutans ( S. mutans) and compare the advantages and disadvantages of the two methods, so as to provide a basis for plasma treatment of dental caries and to enrich the treatment means of dental caries, an atmospheric pressure plasma excitation system was built, and the effects of PJ and PAW on the sterilization rate of S. mutans and the changes of temperature and pH during treatment were studied under different excitation voltage ( U e ) and different excitation time ( t e ). The results showed that in the PJ treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.007, d=2.66) when U e = 7 kV and t e = 60 s, and complete sterilization was achieved at U e = 8 kV and t e = 120 s in the PJ treatment. In contrast, in the PAW treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.029, d = 1.71) when U e = 7 kV and t e = 30 s, and complete sterilization was achieved with PAW treatment when U e = 9 kV and t e = 60 s. Results of the monitoring of temperature and pH showed that the maximum temperature rise during PJ and PAW treatment did not exceed 4.3 °C, while the pH value after PAW treatment would drop to a minimum of 3.02. In summary, the optimal sterilization parameters for PJ were U e =8 kV and 90 s < t e ≤ 120 s, while the optimal sterilization parameters for PAW were U e = 9 kV and 30 s< t e ≤ 60 s. Both treatment methods achieved non-thermal sterilization of S. mutans, where PJ required only a smaller U e to achieve complete sterilization, while at pH < 4.7, PAW only required a shorter t e to achieve complete sterilization, but its acidic environment could cause some chemical damage to the teeth. This study can provide some reference value for plasma treatment of dental caries.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Streptococcus mutans
		                        			;
		                        		
		                        			Dental Caries/therapy*
		                        			;
		                        		
		                        			Sterilization
		                        			;
		                        		
		                        			Temperature
		                        			;
		                        		
		                        			Water
		                        			
		                        		
		                        	
4.Artesunate alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3 inflammasome activation and inflammatory cytokine secretion.
Yinli CAO ; Yazhou SUN ; Qingyang CUI ; Xiaojing HE ; Zhenzhen LI
Chinese Journal of Cellular and Molecular Immunology 2023;39(5):410-415
		                        		
		                        			
		                        			Objective To investigate the protective effect of artesunate on hypoxic-ischemic brain damage (HIBD) and its mechanism in neonatal rats. Methods 7-day-old neonatal SD rats were randomly divided into sham operation group, model group, artesunate 5 mg/kg group, artesunate 10 mg/kg group, artesunate 20 mg/kg group and dexamethasone 6 mg/kg group, with 18 rats in each group. HIBD models were established in groups except for the sham operation group. The sham operation group only needed to separate the left common carotid artery without ligation and nitrogen-oxygen mixed gas ventilation. Each group was injected with drug intraperitoneally right after surgery and the rats in the sham operation group and the model group were injected with an equal volume of normal saline (once a day for a total of 5 times). One hour after the last injection, the rats in each group were scored for neurological defects. After the rats were sacrificed, the brain water content was measured and the pathological changes of the brain tissues of rats were observed. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the neuronal cell apoptosis, and ELISA was applied to detect the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood of each group of rats. Western blot analysis was adopted to detect the protein expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 in the rats brain tissues of each group. Results Compared with the model group, the neurological deficit score was decreased; the pathological damage of brain tissues was relieved; the brain water content was significantly reduced; the apoptosis number of hippocampal neurons was decreased significantly; the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood were significantly reduced; the protein expression levels of NLRP3, ASC and caspase-1 were significantly lowered in the middle-dose and high-dose artesunate groups and the dexamethasone group. Conclusion Artesunate can improve the neurological function, relieve the brain damage, and alleviate the brain edema in neonatal rats with HIBD. It can protect the HIBD, which may be related to the inhibition of NLRP3 inflammasome activation and reduction of inflammatory cytokine secretion.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Animals, Newborn
		                        			;
		                        		
		                        			Artesunate/pharmacology*
		                        			;
		                        		
		                        			Brain/metabolism*
		                        			;
		                        		
		                        			Caspases/metabolism*
		                        			;
		                        		
		                        			Dexamethasone
		                        			;
		                        		
		                        			Hypoxia-Ischemia, Brain/pathology*
		                        			;
		                        		
		                        			Inflammasomes
		                        			;
		                        		
		                        			Interleukin-6/metabolism*
		                        			;
		                        		
		                        			NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			;
		                        		
		                        			Water/metabolism*
		                        			
		                        		
		                        	
5.Effect of early fluid balance on the prognosis in severe acute pancreatitis.
Cong ZHANG ; Yalin OU ; Hongliang QIAN ; Yinxia XU
Chinese Critical Care Medicine 2023;35(5):524-527
		                        		
		                        			OBJECTIVE:
		                        			To observe the correlation between early fluid resuscitation and prognosis in patients with severe acute pancreatitis (SAP).
		                        		
		                        			METHODS:
		                        			SAP patients admitted to the department of critical care medicine of the People's Hospital of Chuxiong Yi Autonomous Prefecture of Yunnan Province from June 2018 to December 2020 were enrolled and analyzed retrospectively. All patients were given the routine treatment according to their condition and relevant diagnostic According to their different prognosis, enrolled patients were divided into death group and survival group. The differences in gender, age, acute physiology and chronic health evaluation II (APACHE II) and Ranson score on admission between the two groups were analyzed. Taking 24 hours as an observation day, the fluid inflow, outflow, and net balance at the first, second, and third 24 hours after admission were recorded, and the ratio of the fluid inflow at the first 24 hours to the total fluid inflow in 72 hours (FV24 h-1 st) was calculated as a study index. Using 33% as the standard, compare the proportion of patients in the two groups who achieved FV24 h-1 st < 33%. The differences of various indicators between the two groups were compared, and the effect of early fluid balance on the prognosis of SAP patients was analyzed.
		                        		
		                        			RESULTS:
		                        			Eighty-nine patients were included in the study (41 in the death group, 48 in the survival group). There were no statistically significant differences on age (years old: 57.6±15.2 vs. 49.5±15.2), gender (male: 61.0% vs. 54.2%), APACHE II score (18.0±2.4 vs. 17.3±2.3), and Ranson score (6.3±1.4 vs. 5.9±1.2) between the death group and the survival group at the time of admission on the intensive care unit (ICU) (all P > 0.05). The fluid intake of the death group in the first 24 hours, the second 24 hours and the third 24 hours after admission to ICU was significantly higher than that of the survival group, and the difference was statistically significant (mL: 4 138±832 vs. 3 535±1 058, 3 883±729 vs. 3 324±516, 3 786±490 vs. 3 212±609, all P < 0.05), and the fluid inflow in the death group at the first 24 hours was greater than 4 100 mL. After treatment, the fluid outflow of the death group at the three 24-hour periods after admission on the ICU was an increasing trend, but it was still significantly less than that of the survival group at the three 24-hour periods (mL: 1 242±465 vs. 1 795±819, 1 536±579 vs. 2 080±524, 1 610±585 vs. 2 932±752, all P < 0.01). Due to the fact that the total fluid inflow and total fluid outflow in the three 24-hour periods in the death group were more than those in the survival group, the net fluid balances in the three 24-hour periods in the death group were still significantly more than those in the survival group finally (mL: 2 896±782 vs. 1 740±725, 2 347±459 vs. 1 243±795, 2 176±807 vs. 338±289, all P < 0.01). There was no difference in FV24 h-1 st between the death group and survival group [FV24 h-1 st > 33%: 56.1% (23/41) vs. 54.2% (26/48), P > 0.05].
		                        		
		                        			CONCLUSIONS
		                        			Fluid resuscitation is an important method for early treatment of SAP, but it also has many adverse reactions. Fluid resuscitation indexes such as fluid inflow, outflow, net balance, and FV24 h-1 st within 24 to 72 hours after admission are related to the prognosis of patients with SAP, and can be used as indicators to evaluate the prognosis of SAP. The optimized fluid resuscitation strategy can improve the prognosis of patients with SAP.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Acute Disease
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Pancreatitis
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Water-Electrolyte Balance
		                        			
		                        		
		                        	
7.Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos.
Shu Yi ZHANG ; Shao Ping ZHANG ; Zi Jin SHAO ; Yuan Zheng FU ; Wen GU ; Hong ZHI ; Jian KONG ; Fu Chang DENG ; Wen Yan YAN ; Juan LIU ; Chao WANG ; Song TANG
Chinese Journal of Preventive Medicine 2023;57(5):693-700
		                        		
		                        			
		                        			Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Zebrafish/metabolism*
		                        			;
		                        		
		                        			Embryo, Nonmammalian/metabolism*
		                        			;
		                        		
		                        			Transcriptome
		                        			;
		                        		
		                        			Oxidative Stress
		                        			;
		                        		
		                        			Water Pollutants, Chemical/metabolism*
		                        			
		                        		
		                        	
8.Revision and prospect of the "Standards for Drinking Water Quality (GB5749-2022)" in China.
Chinese Journal of Preventive Medicine 2023;57(6):801-805
		                        		
		                        			
		                        			The revision of the national standards for drinking water quality is an important, rigorous and delicate endeavor. The paper introduced the revision of this standard, emphasizing the revision principle, overall technical considerations, and revision contents. Recommendations were also proposed for the implementation of this standard.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Drinking Water
		                        			;
		                        		
		                        			Water Quality
		                        			;
		                        		
		                        			Reference Standards
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Water Pollutants, Chemical/analysis*
		                        			;
		                        		
		                        			Water Supply
		                        			
		                        		
		                        	
9.Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality(GB5749-2022)"in China.
Jian Ying HU ; Shi Yi ZHANG ; Min YANG ; Hai Feng ZHANG ; Qi Yue KANG ; Wei AN ; Jia Yi HAN
Chinese Journal of Preventive Medicine 2023;57(6):815-822
		                        		
		                        			
		                        			Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Water Quality
		                        			;
		                        		
		                        			Drinking Water
		                        			;
		                        		
		                        			Fluorocarbons/analysis*
		                        			;
		                        		
		                        			Caprylates/analysis*
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Water Pollutants, Chemical/analysis*
		                        			
		                        		
		                        	
10.Research on the determination of the limit value of perchlorate in the "Standards for Drinking Water Quality(GB5749-2022)" in China.
Sheng Hua GAO ; Wei AN ; Ming YANG ; Bi Xiong YE ; Lan ZHANG
Chinese Journal of Preventive Medicine 2023;57(6):823-825
		                        		
		                        			
		                        			Perchlorate is an environmental pollutant that has been a focus of attention in recent years. It has been detected in many environmental water bodies and drinking water in China, with a high level of presence in some areas of the Yangtze River Basin. The human body may ingest perchlorate through exposure pathways such as drinking water and food, and its main health effect is to affect the thyroid's absorption of iodine. The "Standards for Drinking Water Quality" (GB5749-2022) includes perchlorate as an expanded indicator of water quality, with a limit value of 0.07 mg/L. This article analyzes the technical content related to the determination of hygiene standard limits for perchlorate in drinking water, including the environmental presence level and exposure status of perchlorate, main health effects, derivation of safety reference values, and determination of hygiene standard limits.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Water Quality
		                        			;
		                        		
		                        			Drinking Water
		                        			;
		                        		
		                        			Perchlorates/analysis*
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Water Pollutants, Chemical/analysis*
		                        			
		                        		
		                        	
            
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