Introduction: The Warburg effect refers to a metabolic shift in which cells preferentially utilize aerobic glycolysis rather than oxidative phosphorylation despite adequate oxygen availability. This phenomenon is increasingly recognized as the mechanism for tumor-associated hypoglycemia, or paraneoplastic syndromes such as insulin-like growth factor-2 (IGF-2)– mediated non-islet cell tumor hypoglycemia. We present a case of Warburg effect with management challenges. Case: A 47-year-old male with advanced, treatment-naive retroviral disease presented with chronic cough, progressive right thigh swelling, constitutional symptoms over several months, followed by reduced responsiveness for 2 days prior to admission. Clinically, he was delirious, cachectic with generalized lung crepitations and right thigh mass. He was diagnosed with smear-negative disseminated tuberculosis, and thigh mass was considered either a tuberculous granuloma or sarcoma. During hospitalization, he developed recurrent hypoglycemia with lactatemia despite intravenous dextrose, optimized enteral feeding and a 1-day course of intravenous octreotide. His blood investigations showed full blood count, renal function test, liver function test, and serum ketone within normal range. His arterial blood gas analysis showed type B lactic acidosis with persistent lactatemia. At the time of hypoglycemia (RBS: 3.1 mmol/L), his serum insulin was suppressed, C-peptide was low–normal, morning cortisol was elevated, and IGF-1 was markedly reduced suggestive of non-insulin-mediated hypoglycemia secondary to Warburg effect. Conclusion In patients with retroviral disease and tuberculosis, Warburg effect may lead to poorer clinical outcomes and management may be challenging. Thus, definitive antimicrobial therapy with second generation somatostatin analogues (Pasireotide) may be considered in selected cases to modulate dysregulated hormonal and metabolic pathways. Early identification and timely targeted intervention are crucial to improving outcomes in this high-risk population.
Persistent Infection ; Hypoglycemia

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

Humans ; Persistent Infection ; Orthoreovirus/genetics* ; Reoviridae Infections/veterinary*

Child ; Chronic Disease ; Epstein-Barr Virus Infections/complications* ; Familial Primary Pulmonary Hypertension/complications* ; Herpesvirus 4, Human ; Humans ; Persistent Infection ; Pulmonary Arterial Hypertension

Root canal therapy is the common treatment for endodontic infections. Successful root canal therapy depends on favorable root canal preparation, root canal medication and three-dimensional obturation of the root canal system. The key to successful root canal therapy is to prevent re-infection of the highly complex root canal systems by removing infecious biofilms and bacterial toxins in the root canal system. The present paper reviews the pathogenic mechanism of the Enterococcus faecalis in the harsh environment of root canal system, the inflammation and immunity of refractory periapical periodontitis and the progress of infection control methods.
Dental Pulp Cavity ; Enterococcus faecalis ; Humans ; Periapical Periodontitis/therapy* ; Persistent Infection ; Root Canal Irrigants ; Root Canal Preparation ; Root Canal Therapy

PURPOSE: The vegetative state is a clinical condition with complete unawareness of self and environment, but with preservation of brain-stem functions. Vegetative patients may have nosocomial infections in their wounds, such as pressure sores and infected craniums after cranioplasties. Flap surgery is usually necessary for those wounds, but decision of undergoing surgery is difficult because of various adverse conditions of vegetative patients. We share our experience of several successful flap surgeries in vegetative patients, and evaluate obstacles and requirements to obtain satisfactory results. METHODS: From December 2005 to September 2008, a total of 4 vegetative patients underwent surgeries. In case of 2 patients with infected artificial craniums, scalp reconstructions with free flaps were performed. In case of other 2 patients with huge pressure sores with sepsis, island flap coverage of wounds was performed. Retrospective study was made of hospitalization period, vegetative period, number of surgeries performed, underlying diseases, causative bacteria, and contents of informed consent. RESULTS: Mean hospital day was 14 months and mean vegetative period was 17.5 months. Patients underwent average of 4.5 surgeries under general anesthesia. There were several underlying diseases like hypertension, DM, CHF and chronic anemia. MRSA (Methicilinresistant Staphylococcus aureus) was cultured from every patient's wounds. Informed consent included a warning for high mortality and a need of attentive familial cooperation. CONCLUSION: There are three requirements for doing flap surgeries in vegetative patients. First, to prevent aggravation of brain damage and underlying diseases by general anesthesia, multidisciplinary team approach is needed. Second, operation should be beneficial for prolonging patient's lifespan. Third, because postoperative care is very difficult and long hospitalization is needed, detailed informed consent and highly cooperative attitude of family should be confirmed before operation.
Anemia ; Anesthesia, General ; Bacteria ; Brain ; Cross Infection ; Free Tissue Flaps ; Hospitalization ; Humans ; Hypertension ; Informed Consent ; Methicillin-Resistant Staphylococcus aureus ; Persistent Vegetative State ; Postoperative Care ; Pressure Ulcer ; Retrospective Studies ; Scalp ; Sepsis ; Skull ; Staphylococcus

The use of teicoplanin is increasing with increase in the incidence of wound infections caused by methicillin-resistant Staphylococcus aureus. Teicoplanin has longer half-life than vancomycin, so it can be administerd once daily, whereas vancomycin has to be administered 3~4 times daily. Teicoplanin is known to have lesser side effect profiles than vancomycin, such as skin eruptions, ototoxicity and nephrotoxicity. A 27-year old women in vegetative state had a grade 3 pressure sore at coccyx area. We prescribe teicoplanin to manage wound infected by methicillin-resistant Staphylococcus aureus. Plasma creatine phosphokinase (CPK) was elevated abruptly at 9th day of teicoplanin therapy. Five days after discontinuation of teicoplanin, CPK was normalized. We experienced a case of elevation of plasma creatine phosphokinase associated with teicoplanin.
Coccyx ; Creatine ; Creatine Kinase ; Female ; Half-Life ; Humans ; Incidence ; Methicillin-Resistant Staphylococcus aureus ; Persistent Vegetative State ; Plasma ; Pressure Ulcer ; Skin ; Teicoplanin ; Vancomycin ; Wound Infection