Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective:To explore the strategies and technical points for breast reconstruction using free lower abdominal skin flap transplantation through lateral chest incision.Methods:The data of patients who underwent unilateral breast reconstruction with free lower abdominal flap transplantation using lateral thoracic incision in Hunan Cancer Hospital from October 2022 to March 2023 were retrospectively analyzed. Lateral thoracic incision was used in the recipient area. Firstly suitable radical mastectomy was performed for patients with early onset of breast cancer or recurrence after breast-conserving surgery, and prosthetic dilator removal or breast capsule release was performed for patients with dilator removed or capsular contracture after breast cancer prosthesis reconstruction. After that, the free lower abdominal skin flap breast reconstruction was completed under the same incision. During the operation, blood vessel preparation in the recipient area, skin flap preparation in the donor area, blood vessel anastomosis and breast shaping were completed successively according to the actual situation of the patient. Postoperative observation of complications, follow-up evaluation of reconstructed breast appearance and donor site healing were carred out.Results:A total of 15 female patients were included, aged range from 24 to 57 years old, with an average of 42.3 years old. There were 9 cases of early breast cancer, 2 cases of breast cancer recurrence after breast conserving surgery, 2 cases of breast cancer with dilator removed after breast reconstruction, and 2 cases of capsule contracture after breast cancer prosthesis reconstruction. The length of the lateral chest incision was 7.5-11.2 cm, with an average of 8.7 cm. Six cases were performed with 3/4 of the lower abdominal skin flaps, using a unilateral inferior abdominal vascular pedicle. The volume of the flaps ranged from 19.0 cm × 10.0 cm × 4.5 cm to 23.0 cm × 13.0 cm × 6.0 cm. The weight ranged from 280 to 510 g, with an average of 370 g. Nine cases were performed by cutting the entire lower abdominal skin flap and using bilateral inferior abdominal vascular pedicle. The volume of the skin flaps ranged from 27.0 cm × 11.0 cm × 5.0 cm to 30.0 cm × 14.0 cm × 6.5 cm. The weight ranged from 420 to 730 g, with an average of 530 g. Nine cases were selected as the main trunk of the thoracic and dorsal blood vessels, 4 cases were selected as the anterior serratus branch of the thoracic and dorsal blood vessels, and 2 cases were selected as the main trunk of the thoracic and dorsal blood vessels combined with the anterior serratus branch. One flap experienced venous crisis and the surgery failed, while the remaining 14 flaps survived smoothly. Follow-up period was 6-17 months, with an average of 10.4 months. The reconstructed breast had a satisfactory appearance and texture, without skin flap contraction or deformation. The skin flap donor area and breast recipient area only had linear scars, and there was no significant impact on abdominal wall and shoulder joint function. There was no tumor recurrence or metastasis during follow-up.Conclusion:When the side chest incision is used to perform the related operations of breast cancer radical resection, the free lower abdominal skin flap can be transplanted into the same incision for breast reconstruction. The effect is satisfactory, and the damage of the affected area is further reduced.

Objective:To explore the strategies and technical points for breast reconstruction using free lower abdominal skin flap transplantation through lateral chest incision.Methods:The data of patients who underwent unilateral breast reconstruction with free lower abdominal flap transplantation using lateral thoracic incision in Hunan Cancer Hospital from October 2022 to March 2023 were retrospectively analyzed. Lateral thoracic incision was used in the recipient area. Firstly suitable radical mastectomy was performed for patients with early onset of breast cancer or recurrence after breast-conserving surgery, and prosthetic dilator removal or breast capsule release was performed for patients with dilator removed or capsular contracture after breast cancer prosthesis reconstruction. After that, the free lower abdominal skin flap breast reconstruction was completed under the same incision. During the operation, blood vessel preparation in the recipient area, skin flap preparation in the donor area, blood vessel anastomosis and breast shaping were completed successively according to the actual situation of the patient. Postoperative observation of complications, follow-up evaluation of reconstructed breast appearance and donor site healing were carred out.Results:A total of 15 female patients were included, aged range from 24 to 57 years old, with an average of 42.3 years old. There were 9 cases of early breast cancer, 2 cases of breast cancer recurrence after breast conserving surgery, 2 cases of breast cancer with dilator removed after breast reconstruction, and 2 cases of capsule contracture after breast cancer prosthesis reconstruction. The length of the lateral chest incision was 7.5-11.2 cm, with an average of 8.7 cm. Six cases were performed with 3/4 of the lower abdominal skin flaps, using a unilateral inferior abdominal vascular pedicle. The volume of the flaps ranged from 19.0 cm × 10.0 cm × 4.5 cm to 23.0 cm × 13.0 cm × 6.0 cm. The weight ranged from 280 to 510 g, with an average of 370 g. Nine cases were performed by cutting the entire lower abdominal skin flap and using bilateral inferior abdominal vascular pedicle. The volume of the skin flaps ranged from 27.0 cm × 11.0 cm × 5.0 cm to 30.0 cm × 14.0 cm × 6.5 cm. The weight ranged from 420 to 730 g, with an average of 530 g. Nine cases were selected as the main trunk of the thoracic and dorsal blood vessels, 4 cases were selected as the anterior serratus branch of the thoracic and dorsal blood vessels, and 2 cases were selected as the main trunk of the thoracic and dorsal blood vessels combined with the anterior serratus branch. One flap experienced venous crisis and the surgery failed, while the remaining 14 flaps survived smoothly. Follow-up period was 6-17 months, with an average of 10.4 months. The reconstructed breast had a satisfactory appearance and texture, without skin flap contraction or deformation. The skin flap donor area and breast recipient area only had linear scars, and there was no significant impact on abdominal wall and shoulder joint function. There was no tumor recurrence or metastasis during follow-up.Conclusion:When the side chest incision is used to perform the related operations of breast cancer radical resection, the free lower abdominal skin flap can be transplanted into the same incision for breast reconstruction. The effect is satisfactory, and the damage of the affected area is further reduced.

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.

Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ²=9.719, P=0.008), marital status (χ²=8.496, P=0.014), occupations (χ²=19.462, P<0.001), frequencies of dining out (χ²=5.457, P=0.019), previous Hp test results (χ² =4.131, P=0.042) and test results after treatment (χ²=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.

Objective:Rejection remains the most important factor limiting the survival of transplanted kidneys.Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection,its limitations prevent it from being used as a routine monitoring method.Recently,peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system,however,its application value and strategy in the field of kidney transplantation need further exploration.Additionally,the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases.This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection(TCMR)and antibody-mediated rejection(ABMR),as well as their diagnostic value,in conjunction with routine blood tests. Methods:A total of 154 kidney transplant recipients,who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December,2021,were selected as the study subjects.They were assigned into a stable group,a TCMR group,and an ABMR group,based on the occurrence and type of rejection.The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups.The transplant kidney function,routine blood tests,and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. Results:The stable,TCMR group,and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys(all P>0.05).However,the post-transplant duration was significantly longer in the ABMR group compared with the stable group(P<0.001)and the TCMR group(P<0.05).Regarding kidney function,serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group(both P<0.01),with the TCMR group also showing higher levels than the stable group(P<0.01).Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group(P<0.01),with no statistically significant difference between TCMR and ABMR groups(P>0.05).The estimated glomerular filtration rate(eGFR)was lower in both TCMR and ABMR groups compared with the stable group(both P<0.01).In routine blood tests,the ABMR group had lower hemoglobin,red blood cell count,and platelet count than the stable group(all P<0.05).The TCMR group had higher neutrophil percentage(P<0.05)and count(P<0.05)than the stable group,and the ABMR group had a higher neutrophil percentage than the stable group(P<0.05).The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups(all P<0.05).Both TCMR and ABMR groups had lower basophil percentage and count,as well as lower lymphocyte percentage and count,compared with the stable group(all P<0.05).There were no significant differences in monocyte percentage and count among the 3 groups(all P>0.05).In lymphocyte subpopulations,the TCMR and ABMR groups had lower counts of CD45+cells and T cells compared with the stable group(all P<0.05).The TCMR group also had lower counts of CD4+T cells,NK cells,and B cells than the stable group(all P<0.05).There were no significant differences in the T cell percentage,CD4+T cell percentage,CD8+T cell percentage and their counts,CD4+/CD8+T cell ratio,NK cell percentage,and B cell percentage among the stable,TCMR,and ABMR groups(all P>0.05). Conclusion:The occurrence of rejection leads to impaired transplant kidney function,accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients.The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.

Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

OBJECTIVE: This study aimed to explore the association between humidity exposure and the risk of cardiovascular disease (CVD), utilizing follow-up data and relative humidity (RH) metric assessments. METHODS: We extracted the baseline data from the China Hypertension Survey (CHS) of 24,510 enrolled participants aged ≥ 35 years without a history of CVD between 2012 and 2015 and followed them up from 2018 to 2019. The National Meteorological Information Center (NMIC) of the China Meteorological Administration (CMA) provided the quality-controlled relative humidity (RH) datasets. Cox proportional hazards models were used to estimate hazard ratios ( HRs) for CVD in relation to RH. RESULTS: During the follow-up period (2018-2019), 973 patients with CVD were identified. The HR of CVD risk was 1.17 (95% CI: 1.04-1.31) per 10% increase in summer mean RH. Compared with participants in the 3 ^rd quintile group, those in the 1 ^st and 5 ^th quintiles of RH had a higher risk of CVD. For summer mean RH, the HRs (95% CIs) for the 1 ^st and 5 ^th quintiles were 1.34 (1.04-1.71) and 1.44 (1.14-1.83), respectively. The relationship ("U" shape) between summer mean RH and the risk of CVD was nonlinear. Stratified analyses indicated that the risk of CVD was substantially influenced by the summer mean RH in female, older individuals, and those in southern China. CONCLUSION Unsuitable (too high or low) humidity environments affect the risk of CVD. Our study highlights those future policies for adapting to climate change should consider the humidity-CVD relationship.
Humans ; Humidity/adverse effects* ; Cardiovascular Diseases/etiology* ; Female ; Male ; Middle Aged ; Prospective Studies ; China/epidemiology* ; Adult ; Aged ; Risk Factors ; Proportional Hazards Models ; Seasons