Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Humans ; Child ; Retrospective Studies ; Thrombocytosis/etiology*

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi. METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data. RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs. CONCLUSION HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
Humans ; HIV-1/genetics* ; HIV Infections ; Drug Users ; Phylogeny ; Bayes Theorem ; China/epidemiology* ; Genotype

Objective: To investigate the regularity of sensory recovery after repairing the wounds on the wrist and back of hand with anterolateral femoral flap without nerve anastomosis. Methods: A cross-sectional study was conducted. From January 2018 to December 2020, patients who underwent free anterolateral femoral flaps without nerve anastomosis to repair wounds on the wrist and back of hand and met the inclusion criteria in Changshu Hai Yu Health Centre and Suzhou Ruihua Orthopedic Hospital were included in this study. Depending on the time interval between the day of the patient's surgery and the day of the cross-sectional survey, 80 patients were divided into 6-month group (15 males and 5 females, aged 22-63 years), 12-month group (16 males and 4 females, aged 21-65 years), 18-month group (15 males and 5 females, aged 25-61 years), and 24-month group (14 males and 6 females, aged 20-65 years), with 20 patients in each group. The area of skin and soft tissue defects after debridement ranged from 6.0 cm×4.5 cm to 18.0 cm×9.0 cm. Anterolateral femoral flaps were cut with areas of 7 cm×5 cm to 20 cm×10 cm and a thickness of 1.0 to 2.5 cm. Each transplanted flap was divided into A (proximal), B/D (bilateral), C (distal), and E (central) regions. The pain sensation, touch sensation, cold sensation, warmth sensation, and two-point discrimination (2-PD) in the aforementioned five regions and the differences in the five senses of the whole flap were tested and compared. Data were statistically analyzed with one-way analysis of variance, Fisher's exact probability test, chi-square test, or McNemar test. Results: In A region of anterolateral femoral flap without nerve anastomosis, compared with those in 6-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 12-month group were significantly recovered (with χ² values of 10.10, 14.55, 12.13, and 4.29, respectively, P<0.05 or P<0.01); compared with that in 12-month group, the warmth sensation of flap of patients in 18-month group recovered significantly (χ²=5.23, P<0.05). In B region, compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of flap of patients in 12-month group recovered significantly (with χ² values of 5.58, 3.96, and 4.29, respectively, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 5.58, 3.96, 7.03, and 12.38, respectively, P<0.05 or P<0.01). In C region, compared with that in 6-month group, the pain sensation of flap of patients in 12-month group recovered significantly (χ²=4.80, P<0.05); Compared with that in 12-month group, the warmth sensation of flap of patients in 18-month group recovered significantly (χ²=10.16, P<0.01). In D region, compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of flap of patients in 12-month group recovered significantly (with χ² values of 5.58, 4.29, and 3.96, respectively, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 5.58, 4.29, 3.96, and 10.10, respectively, P<0.05 or P<0.01). In E region, compared with that in 6-month group, the cold sensation of flap of patients in 12-month group recovered significantly (χ²=4.80, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 6.47, 4.91, and 9.23, respectively, P<0.05 or P<0.01). The five senses in the 5 regions of flap of patients in 24-month group were similar to those in 18-month group (P>0.05). The recovery of 2-PD in the 5 regions of flap of patients was similar between the two adjacent groups (P>0.05). In 12-month group, the recoveries of pain sensation, touch sensation, and cold sensation of flap of patients in A region were better than those in the other 4 regions (P<0.05 or P<0.01), the recovery of warmth sensation was better than that of B region, C region, and E region (P<0.05 or P<0.01); in 18-month group, the recovery of pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in A region of was better than those in area C region (P<0.05). Compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of the whole flap of patients in 12-month group recovered significantly (with χ² values of 7.62, 7.03, and 5.58, respectively, P<0.05 or P<0.01). Compared with the 12-month group in which 10, 11, 10, and 4 patients had a recovery of pain, touch sensation, cold sensation, and warmth sensation in the whole flap, the 18-month group had significantly more patients with sensations recovered, which were 17, 17, 16, and 14, respectively (with χ² values of 5.58, 4.29, 3.96, and 10.10, respectively, P<0.05 or P<0.01). The five senses of the whole flap of patients in 24-month group were similar to those in 18-month group (P>0.05). Conclusions: In the anterolateral femoral flap without nerve anastomosis for repairing wounds on the wrist and back of hand, the sensation gradually recovered from the proximal end to the distal end. The sensation of touch, pain, and cold began to recover from 6 months after operation, and entered the stable recover period at 18 months after operation. Warmth sensation began to recover from 12 months after operation, and entered the stable recovery period at 18 months after operation. The 2-PD of most flaps was still not recovered 2-year after operation.
Male ; Female ; Humans ; Wrist ; Cross-Sectional Studies ; Touch/physiology* ; Pain ; Anastomosis, Surgical

Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.
China ; Drugs, Chinese Herbal ; Humans ; Industry ; Medicine, Chinese Traditional ; Policy

Today, nonalcoholic fatty liver disease remains the most dominant chronic liver disease. Cyclic guanosine monophosphate-adenosine monosphosphate synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of cyclic guanosine monophosphate, activates stimulator of interferon genes (STING), and releases type-I interferon cytokines to trigger immune responses. Exogenous or endogenous DNA acts as a cGAS ligand to activate the cGAS-STING signaling pathway, which plays a role in hepatitis, nonalcoholic fatty liver disease, liver cancer and other diseases, and affects liver disease progression and metabolism through mechanisms such as autophagy. This article reviews the activation of cGAS-STING pathway and its molecular immunological role in nonalcoholic fatty liver disease progression.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion. METHODS: A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias. RESULTS: The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ± 27.1 vs. 95.5 ± 26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups. CONCLUSIONS In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.
Glucose/therapeutic use* ; Histidine ; Humans ; Infant, Newborn ; Mannitol ; Organ Preservation Solutions ; Potassium Chloride/therapeutic use* ; Prognosis ; Retrospective Studies ; Stroke Volume ; Tryptophan ; Ventricular Function, Left

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
Abdomen ; surgery ; China ; Drainage ; methods ; Evidence-Based Medicine ; Humans ; Practice Guidelines as Topic ; Societies, Medical ; organization & administration ; Surgical Wound Infection ; prevention & control ; Traumatology ; organization & administration ; Vacuum

Danhong injection (DHI) and ceftriaxone sodium were used in combination based on their experimental uses in clinic. This study was designed to investigate the impact of ceftriaxone on pharmacokinetics and pharmacodynamics of the phenolic acids from DHI. After administration of DHI for 7 d, ceftriaxone (CFTX) was combined with DHI for the next 7 d in adult male Sprague-Dawley (SD) rats. All the drugs were administered through caudal vein. UHPLC-TQ-MS was applied in determining the plasma concentration of p-coumaric acid (p-CA), salvianolic acid D (SaD), rosmarinic acid (RA) and salvianolic acid B (SaB). The pharmacokinetic parameters of the combination group or the Danhong injection alone group were calculated by statistical moment method, C_max and the average of the area under the curve AUC_0-t using 90% confidence interval of the bioequivalence and bioavailability degree module in DAS 3.2.8 statistic software. The results showed that C_max of p-CA, SaD, RA and SaB were unqualified within 90% confidence intervals for bioequivalence statistics. And the results showed that AUC_0-t of SaD, RA and SaB within 90% confidence intervals for bioequivalence statistics were unqualified. There were no significant difference in the t_max (P>0.05). The results of anticoagulation in vivo showed that the international normalized ratio (INR), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) were significantly increased when combined with CFTX (P<0.05 or P<0.01). The results in antithrombotic effects revealed that the thromboxane B₂ (TXB₂) level in serum was significantly decreased (P<0.01) in the combination group compared with Danhong injection alone. However, there was no significant difference in antiplatelet effects. These results suggest that CFTX may enhance the anticoagulation and antithrombotic effects of DHI through altering pharmacokinetics and pharmacodynamics in SD rats.

BACKGROUNDMitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes.

METHODSWe manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells. One-way analysis of variance and Student's t-test were performed to determine the statistical significance between the groups.

RESULTSOverexpression of MFN2 enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 ± 10.130 vs. 266.940 ± 10.170, P = 0.000), calcineurin (0.513 ± 0.014 vs. 0.403 ± 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs) activation (1.040 ± 0.086 vs. 0.700 ± 0.115, P = 0.005), whereas depletion of MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+ (141.140 ± 14.670 vs. 267.060 ± 9.230, P = 0.000), calcineurin (0.054 ± 0.030 nmol/L vs. 0.404 ± 0.063 nmol/L, P = 0.000), and NFAT activation (0.500 ± 0.025 vs. 0.720 ± 0.061, P = 0.012). Furthermore, upregulated calcineurin partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity evidenced by elevations in T cell proliferation (1.120 ± 0.048 vs. 0.580 ± 0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 ± 24.100 vs. 175.330 ± 12.900 pg/ml, P = 0.000), and the interferon-γ/IL-4 ratio (3.080 ± 0.156 vs. 0.953 ± 0.093, P = 0.000). Meanwhile, calcineurin activity inhibitor depleted the positive effects of overexpressed MFN2 on T cells function.

CONCLUSIONSOur findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.