Objective:To explore the role of glutathione peroxidase 4 (GPX4)-dependent ferroptosis in diclofenac-induced kidney injury.Methods:Human kidney tubular epithelial cells (HK-2 cells) were cultured and then divided into 3 groups: control group, diclofenac group, and iron death inhibitor ferrostatin-1 (Fer-1) group. The same amount of 1% Fer-1 (final concentration 10 μmol/L) and phosphate buffered saline was respectively added to cells in the Fer-1 group and the other 2 groups. After 48 hours of culture, diclofenac 200 μmol/L was added to cells in the diclofenac group and the Fer-1 group. The cell viability of each group was detected by cell counting kit-8 (CCK-8). The cell cycle, apoptosis and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. The levels of intracellular iron ion, lactate dehydrogenase (LDH), malondialdehyde (MDA) and GPX4 were detected by enzyme-linked immunosorbent assay. The expression level of GPX4 was detected by Western blotting method.Results:Compared with the control group, the cell viability and G1 phase cell percentage of the diclofenac group were significantly lower, and compared with the diclofenac group, those were significantly higher (all P<0.05). The apoptosis rate of diclofenac group was significantly higher than that of the control group ( P<0.05), but there was no significant difference in apoptosis rate between Fer-1 group and diclofenac group ( P>0.05). Compared with the control group, the intracellular ROS, iron content, LDH, and MDA levels were significantly higherin the diclofenac group, while the expression level of GPX4 was lower (all P<0.05). However, the ROS, iron content, LDH, and MDA levels in the Fer-1 group were lower than those in the diclofenac group, while GPX4 expression was higher than that in the diclofenac group (all P<0.05). Conclusion:Diclofenac can induce ferroptosis in HK-2 cells and inhibiting the ferroptosis can alleviate cell injury, suggesting that GPX4-dependent ferroptosis may be involved in kidney injury induced by diclofenac.

Objective:To explore the role of glutathione peroxidase 4 (GPX4)-dependent ferroptosis in diclofenac-induced kidney injury.Methods:Human kidney tubular epithelial cells (HK-2 cells) were cultured and then divided into 3 groups: control group, diclofenac group, and iron death inhibitor ferrostatin-1 (Fer-1) group. The same amount of 1% Fer-1 (final concentration 10 μmol/L) and phosphate buffered saline was respectively added to cells in the Fer-1 group and the other 2 groups. After 48 hours of culture, diclofenac 200 μmol/L was added to cells in the diclofenac group and the Fer-1 group. The cell viability of each group was detected by cell counting kit-8 (CCK-8). The cell cycle, apoptosis and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. The levels of intracellular iron ion, lactate dehydrogenase (LDH), malondialdehyde (MDA) and GPX4 were detected by enzyme-linked immunosorbent assay. The expression level of GPX4 was detected by Western blotting method.Results:Compared with the control group, the cell viability and G1 phase cell percentage of the diclofenac group were significantly lower, and compared with the diclofenac group, those were significantly higher (all P<0.05). The apoptosis rate of diclofenac group was significantly higher than that of the control group ( P<0.05), but there was no significant difference in apoptosis rate between Fer-1 group and diclofenac group ( P>0.05). Compared with the control group, the intracellular ROS, iron content, LDH, and MDA levels were significantly higherin the diclofenac group, while the expression level of GPX4 was lower (all P<0.05). However, the ROS, iron content, LDH, and MDA levels in the Fer-1 group were lower than those in the diclofenac group, while GPX4 expression was higher than that in the diclofenac group (all P<0.05). Conclusion:Diclofenac can induce ferroptosis in HK-2 cells and inhibiting the ferroptosis can alleviate cell injury, suggesting that GPX4-dependent ferroptosis may be involved in kidney injury induced by diclofenac.

Objective:To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.Methods:Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.Results:A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm [20 (36.4%)] or cold [15 (27.3%)] in property, and mostly bitter and pungent in taste [bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)]. The channel tropisms were mainly liver, lung, spleen, and kidney [58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)], and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.Conclusions:Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Objective:To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.Methods:Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.Results:A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm [20 (36.4%)] or cold [15 (27.3%)] in property, and mostly bitter and pungent in taste [bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)]. The channel tropisms were mainly liver, lung, spleen, and kidney [58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)], and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.Conclusions:Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Objective:To investigate the protective effect of reduced glutathione (GSH) on diclo-fenac-induced acute kidney injury (AKI) in rats and its mechanism.Methods:Thirty-three male 8-week-old specified pathogen-free SD rats were randomly divided into control, model, and GSH groups (11 rats in each group) according to a random number table method. Diclofenac sodium solution (200 mg/kg) was intragastrically administered to rats in the model group and GSH group to establish the AKI model. Thirty minutes later, rats in the GSH group were treated with intragastric administration of GSH solution (500 mg/kg), while rats in the control and model groups were with 0.9% sodium chloride injection of equal volume. After 24 hours of administration, blood sample was collected and kidneys were isolated. Kidney function [blood urea nitrogen (BUN), serum creatinine (Scr)], kidney histopathology, and serum and kidney tissue oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and the inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) were examined. The results of each examination results among rats of the 3 groups were compared.Results:The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN: (14.34±8.47) mmol/L vs. (7.89±2.20) and (8.46±3.58) mmol/L; Scr: (34.44±6.56) μmol/L vs. (24.77±9.50) and (29.28±4.33) μmol/L, all P<0.05]. Glomerular and tubular morphological changes were observed in both model and GSH rats, but the change in rats of GSH group was less severe than that of the model group. The mean levels of MDA, TNF-α, and IL-6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA: (9.5±0.2) nmol/ml vs. (10.2±0.6) nmol/ml, (3.6±0.3) nmol/ml vs. (4.0±0.2) nmol/ml; TNF-α: (2.9±2.5) pg/ml vs. (5.4±3.0) pg/ml, (420.9±40.3) pg/ml vs. (470.4±31.3) pg/ml; IL-6: (92.1±34.4) pg/ml vs. (123.9±16.6) pg/ml, (7 547±604) pg/ml vs. (8 047±470) pg/ml, all P<0.05], while the activity of SOD was significantly higher than that in the model group[(102.8±2.8) U/ml vs. (99.7±4.1) U/ml, (387.0±12.7) U/ml vs. (375.9±11.7) U/ml, all P<0.05]. Conclusion:GSH has a protective effect on diclofenac-induced acute kidney injury in rats, and its possible mechanism is to inhibit oxidative stress and inflammatory reactions.

Objective:To investigate the protective effect of reduced glutathione (GSH) on diclo-fenac-induced acute kidney injury (AKI) in rats and its mechanism.Methods:Thirty-three male 8-week-old specified pathogen-free SD rats were randomly divided into control, model, and GSH groups (11 rats in each group) according to a random number table method. Diclofenac sodium solution (200 mg/kg) was intragastrically administered to rats in the model group and GSH group to establish the AKI model. Thirty minutes later, rats in the GSH group were treated with intragastric administration of GSH solution (500 mg/kg), while rats in the control and model groups were with 0.9% sodium chloride injection of equal volume. After 24 hours of administration, blood sample was collected and kidneys were isolated. Kidney function [blood urea nitrogen (BUN), serum creatinine (Scr)], kidney histopathology, and serum and kidney tissue oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and the inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) were examined. The results of each examination results among rats of the 3 groups were compared.Results:The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN: (14.34±8.47) mmol/L vs. (7.89±2.20) and (8.46±3.58) mmol/L; Scr: (34.44±6.56) μmol/L vs. (24.77±9.50) and (29.28±4.33) μmol/L, all P<0.05]. Glomerular and tubular morphological changes were observed in both model and GSH rats, but the change in rats of GSH group was less severe than that of the model group. The mean levels of MDA, TNF-α, and IL-6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA: (9.5±0.2) nmol/ml vs. (10.2±0.6) nmol/ml, (3.6±0.3) nmol/ml vs. (4.0±0.2) nmol/ml; TNF-α: (2.9±2.5) pg/ml vs. (5.4±3.0) pg/ml, (420.9±40.3) pg/ml vs. (470.4±31.3) pg/ml; IL-6: (92.1±34.4) pg/ml vs. (123.9±16.6) pg/ml, (7 547±604) pg/ml vs. (8 047±470) pg/ml, all P<0.05], while the activity of SOD was significantly higher than that in the model group[(102.8±2.8) U/ml vs. (99.7±4.1) U/ml, (387.0±12.7) U/ml vs. (375.9±11.7) U/ml, all P<0.05]. Conclusion:GSH has a protective effect on diclofenac-induced acute kidney injury in rats, and its possible mechanism is to inhibit oxidative stress and inflammatory reactions.

Tofacitinib is a novel targeted drug for the treatment of rheumatoid arthritis. With the entry into the medical insurance catalogue, the drug will usher in a new era. This paper reviews the effectiveness and safety of tofacitinib in the treatment of rheumatoid arthritis. Generally speaking, tofacitinib has definite efficacy, few adverse reactions, and controllable safety. Tofacitinib has an advantage over biological agents, that is, tofacitinib can be orally administered. Therefore, tofacitinib is especially developed for patients who have a poor response to or who are intolerant to disease-modifying antirheumatic drugs and biological agents. However, the effectiveness and safety of tofacitinib in a Chinese population need to be confirmed by more studies.

A 40-year-old female patient was treated with sulfasalazine 0.75 g thrice daily for spondyloarthritis. On the 20th day of medication, the patient developed skin rash all over the body, which was gradually aggravated and accompanied by fever, lymphadenectasis, and splenomegaly. Laboratory tests revealed the white blood cell count 14.4×10 9/L, the eosinophil count 0.82×10 9/L, the urinary occult blood (+++) , alanine aminotransferase 84 U/L, and aspartate aminotransferase 96 U/L. Drug-induced hypersensitivity syndrome was diagnosed and considered to be related to sulfasalazine. Sulfasalazine was discontinued and intravenous infusions of methylprednisolone combined with human immunoglobulin were given. At the same time, anti-infection, anti-allergy, and liver-protective treatments were given additionally. After 8 days of treatments, the rash began to subside and itching was improved; after 18 days, the rash basically subsided and laboratory tests showed the results returned to normal.

A 4 years and 7 months old boy was treated with IV infusions of azithromycin 0.16 g once daily and methylprednisolone sodium succinate 32 mg once daily and oral amoxicillin and clavulanate potassium for suspension 228.5 mg twice daily for bronchopneumonia complicated with multiple co-infections with mycoplasma, viruses, and bacteria. After 6 days of treatments, the boy′s symptoms were improved and his body temperature returned to normal. On the 7th day of treatments, the boy developed rash with itching, which subsided on the same day after symptomatic treatments. Amoxicillin and clavulanate potassium and azithromycin were discontinued, but the child still developed rash every time after IV infusion of methylprednisolone sodium succinate, which could subside later that day. After withdrawal of methylprednisolone sodium succinate, the boy′s rash did not recur.

A 40-year-old female patient was treated with sulfasalazine 0.75 g thrice daily for spondyloarthritis. On the 20th day of medication, the patient developed skin rash all over the body, which was gradually aggravated and accompanied by fever, lymphadenectasis, and splenomegaly. Laboratory tests revealed the white blood cell count 14.4×10 9/L, the eosinophil count 0.82×10 9/L, the urinary occult blood (+++) , alanine aminotransferase 84 U/L, and aspartate aminotransferase 96 U/L. Drug-induced hypersensitivity syndrome was diagnosed and considered to be related to sulfasalazine. Sulfasalazine was discontinued and intravenous infusions of methylprednisolone combined with human immunoglobulin were given. At the same time, anti-infection, anti-allergy, and liver-protective treatments were given additionally. After 8 days of treatments, the rash began to subside and itching was improved; after 18 days, the rash basically subsided and laboratory tests showed the results returned to normal.